Abstracts of Recent Publications on Transcranial Magnetic Stimulation for Depression.

Compiled by Ivan Goldberg, M.D.

Tijdschr Psychiatr. 2011;53(6):343-53.

[Transcranial magnetic stimulation as a treatment for depression].

[Article in Dutch]

Schutter DJ.

Universitair Hoofddocent Verbonden aan de Afdeling Psychologische Functieleer aan
de Universiteit van Utrecht. d.schutter@uu.nl

BACKGROUND: The high incidence of depressive disorder in the Netherlands calls
for additional forms of therapy. Transcranial magnetic stimulation (TMS) is a
form of non-invasive brain stimulation that has been investigated in the last 15
years in order to find out whether this form of stimulation is effective in the
treatment of depression.
AIM: To discover whether TMS has proved effective in the treatment of depressed
RESULTS: Results show that tms treatment is safe when applied to the frontal
lobes of the cerebral cortex and that the therapeutic effect is comparable to the
effect of psychotherapy and antidepressants. Future studies should concentrate on
an increase in efficiency by providing more insight into the working mechanisms
and the effect of individual differences. Follow-up studies are needed to
investigate the duration of the antidepressive effect.
CONCLUSION: TMS seems to be a promising tool for the treatment of depressive
disorders. However, there are many questions and uncertainties about the
efficiency and applicability of TMS.
PMID: 21674447 [PubMed – indexed for MEDLINE] Prescrire Int. 2011 May;20(116):128-33.

Treatment-resistant depression: no panacea, many uncertainties. Adverse effects
are a major factor in treatment choice.

[No authors listed]

At least 50% of patients with depression do not enter remission after several
weeks of antidepressant therapy. To determine the treatment options and their
respective risk-benefit balances in this setting, we reviewed the literature
using the standard Prescrire methodology. Clinical trials and epidemiological
studies show that depression should only be considered drug-resistant after at
least 6 weeks of therapy. After assessing residual symptoms and their impact on
the patient’s quality of life, a search should be made for factors responsible
for the persistence of depression, such as the patient’s environment, a
psychiatric or somatic disorder, and drug intake or addiction. Increasing the
dose of the first-line antidepressant is only based on weak evidence. Trials
comparing continuing the first-line antidepressant versus switching to another
pharmacological class have yielded conflicting results. A switch may benefit some
patients, but the elimination half-life of the discontinued drug must be taken
into account to limit the risk of interactions during the transition. Combining
two antidepressants mainly increases the risk of adverse effects, without a
tangible clinical benefit. Two meta-analyses suggest that adding a so-called
atypical neuroleptic to ongoing antidepressant therapy leads to 1 extra remission
per 7 to 10 treated patients, but also to treatment cessation due to adverse
effects in 8% to 9% of cases. Older neuroleptics have not been properly evaluated
in this setting. Comparative trials suggest that lithium may have a certain
antidepressant effect in this setting, but there is no firm evidence that adding
lithium increases the chances of remission. Lithium has a narrow therapeutic
margin and overdose can be fatal; the blood lithium concentration must therefore
be monitored. Adding an antiepileptic or a psychostimulant is more harmful than
beneficial. Adding a thyroid hormone, a benzodiazepine, buspirone or pindolol has
no proven antidepressive effect. Four trials, each including fewer than 20
patients, have assessed the efficacy of psychotherapy in patients with
treatment-resistant depression. Two of them provided positive results.
Electroconvulsive therapy is probably effective for some patients with refractory
depression but it necessitates general anaesthesia and carries a risk of memory
disorders. Vagal nerve electrostimulation has no proven efficacy. Transcranial
magnetic stimulation seems to have some efficacy and few adverse effects, but its
optimal modalities remain to be determined. In practice, when the patient and
doctor decide to attempt second-line therapy for treatment-resistant depression,
adverse effects must be taken into account in the choice of drug(s). Maintaining
a good quality relationship between patient and doctor may be more important than
attempting to obtain remission “at any cost”.
PMID: 21648180 [PubMed – indexed for MEDLINE] Psychiatr Pol. 2011 Jan-Feb;45(1):117-34.

[Transcranial magnetic stimulation in treatment of depression–question of
placebo and warranting of blind conditions, as well as other methodological

[Article in Polish]

Zyss T.

Oddzial Kliniczny Kliniki Psychiatrii Doros?ych Szpitala Uniwersyteckiego w

Transcranial magnetic stimulation TMS is the first new physical technique used
since 1993 in investigations on their antidepressant efficacy. Literature
investigations show, that the majority of clinical investigations were carried
out in the control to placebo and were double-blinded. The lack of a possibility
of obtaining the true placebo conditions causes, that the terms of double
blinding, as declared by different authors are less credible. TMS stimulation
does not allow even single-blinding of clinical investigations.
PMID: 21614837 [PubMed – indexed for MEDLINE] Dialogues Clin Neurosci. 2011;13(1):139-45.

Neurobiological mechanisms of repetitive transcranial magnetic stimulation on the
underlying neurocircuitry in unipolar depression.

Baeken C, De Raedt R.

Department of Psychiatry and Center for Neurosciences, Vrije Universiteit Brussel
(VUB), Brussels, Belgium. chris.baeken@uzbrussel.be

For nearly two decades now, transcranial magnetic stimulation (TMS) has been
available as a noninvasive clinical tool to treat patients suffering from major
depression. In this period, a bulk of animal and human studies examined TMS
parameters to improve clinical outcome. However, the neurobiological mechanisms
underlying mood changes remain an important focus of research. In addition to
having an effect on neuroendocrinological processes, neurotransmitter systems,
and neurotrophic factors, TMS may not only affect the stimulated cortical
regions, but also those connected to them. Therefore, we will review current
human data on possible neurobiological mechanisms of repetitive (r) TMS
implicated in the deregulated neurocircuitry present in unipolar depression.
Furthermore, as the rTMS application can be considered as a “top-down” neuronal
intervention, we will focus on the neuronal pathways linked with the stimulated
area and we will present an integrative model of action.
PMID: 21485753 [PubMed – indexed for MEDLINE] J ECT. 2011 Mar;27(1):18-25.

Safety, tolerability, and effectiveness of high doses of adjunctive daily left
prefrontal repetitive transcranial magnetic stimulation for treatment-resistant
depression in a clinical setting.

Hadley D, Anderson BS, Borckardt JJ, Arana A, Li X, Nahas Z, George MS.

Brain Stimulation Laboratory, Psychiatry Department, Medical University of South
Carolina, USA. DakotaHadley88@gmail.com

OBJECTIVE: Daily left prefrontal repetitive transcranial magnetic stimulation
(rTMS) recently received Food and Drug Administration (FDA) approval for the
treatment of depression and offers an alternative to traditional approaches. This
approval was based on a study using 3000 stimuli per day (15,000 stimuli per
week) in adults with unipolar depression not taking antidepressant medications.
Several meta-analyses suggest a dose-response relationship with TMS. This study
was carried out before US FDA approval to test the safety, tolerability, and
effectiveness of adjunctive high-dose left prefrontal rTMS in a clinical setting
with particular attention to safety of higher doses and potential interactions
with antidepressant medications, speed of response, and effects on suicidality.
METHOD: We enrolled 19 patients who were in a current major depressive episode
with treatment-resistant unipolar or bipolar depression and treated them in their
acute episode and in a maintenance fashion for 18 months. The patients received
daily left prefrontal rTMS at 120% resting motor threshold, 10 Hz, 5 seconds on,
and 10 seconds off and for a mean of 6800 stimuli per session (34,000 stimuli per
week), more than twice the dose delivered in the pivotal FDA trial. All patients
continued antidepressant medication throughout the rTMS treatment; thus rTMS was
an adjunctive treatment. We measured adverse effects, depression, quality of
life, suicidal ideation, and social and physical functioning.
RESULTS: These higher rTMS doses were well tolerated without significant adverse
effects or adverse events. All measured dimensions showed improvement, with many
showing improvement in 1 to 2 weeks. Of perhaps most importance, suicidal
ideation diminished in 67% of the patients after just 1 week.
CONCLUSIONS: These uncontrolled data suggest that higher doses of daily left
prefrontal rTMS may safely be used in outpatients with major depressive episode
even as an adjunctive treatment.
PMID: 21343710 [PubMed – indexed for MEDLINE] Ann Clin Psychiatry. 2011 Feb;23(1):48-62.

The emerging use of technology for the treatment of depression and other
neuropsychiatric disorders.

Howland RH, Shutt LS, Berman SR, Spotts CR, Denko T.

Department of Psychiatry, Western Psychiatric Institute and Clinic, University of
Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. HowlandRH@upmc.edu

BACKGROUND: Our objective is to review emerging technologies intended for the
treatment of depression and other neuropsychiatric disorders.
METHODS: These technologies include repetitive transcranial magnetic stimulation
(rTMS), magnetic seizure therapy (MST), vagus nerve stimulation (VNS), deep brain
stimulation (DBS), cortical brain stimulation (CBS), and quantitative
electroencephalography (QEEG).
RESULTS: The rationale for these technologies, their mechanisms of action, and
how they are used in clinical practice are described. rTMS and VNS are effective
for treatment-resistant depression. DBS is effective for resistant
obsessive-compulsive disorder. QEEG can help predict a patient’s response to an
antidepressant. All of these technologies continue to be investigated in
treatment studies.
CONCLUSIONS: As these and other emerging technologies for depression and other
neuropsychiatric disorders are development and applied, psychiatrists should
understand the rationale for these modalities, how they work, and how they can be
used in clinical practice.
PMID: 21318196 [PubMed – indexed for MEDLINE] J Womens Health (Larchmt). 2011 Feb;20(2):255-61.

An open label pilot study of transcranial magnetic stimulation for pregnant women
with major depressive disorder.

Kim DR, Epperson N, Paré E, Gonzalez JM, Parry S, Thase ME, Cristancho P, Sammel
MD, O’Reardon JP.

Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania
19104, USA. drkim@mail.med.upenn.edu

OBJECTIVE: Despite the data that major depressive disorder (MDD) is common during
pregnancy and that pregnant women prefer nonmedication treatment options, there
is a paucity of research examining alternative treatments for this special
population. We present the results of an open label pilot study examining
treatment with transcranial magnetic stimulation (TMS) in pregnant women with
METHODS: Ten women with MDD in the second or third trimester of pregnancy were
treated with 20 sessions of 1-Hz TMS at 100% of motor threshold (MT) to the right
dorsolateral prefrontal cortex. The total study dose was 6000 pulses. Antenatal
monitoring was performed during treatment sessions 1, 10, and 20.
RESULTS: Seven of ten (70%) subjects responded (decrease ?50% in Hamilton
Depression Rating Scale [HDRS-17] scores). No adverse pregnancy or fetal outcomes
were observed. All infants were admitted to the well baby nursery and were
discharged with the mother. Mild headache was the only common adverse event and
was reported by 4 of 10 (40%) subjects.
CONCLUSIONS: TMS appears to be a promising treatment option for pregnant women
who do not wish to take antidepressant medications.
PMID: 21314450 [PubMed – indexed for MEDLINE] Psychiatr Danub. 2010 Nov;22 Suppl 1:S135-6.

Intensive rTMS applications in difficult to treat psychiatric patients: some

Zeeuws D, Santermans L, Baeken C, Vanderbruggen N.

Department of Psychiatry, University Hospital (UZ Brussel), Laarbeeklaan 101,
1090 Brussels, Belgium. dieter.zeeuws@uzbrussel.be

Despite adherence to treatment guidelines, some patients are resistant to several
psychopharmacological interventions. Guidelines to overcome treatment resistance
are scarce and new treatment modalities are needed. When confronted with
psychopharmacological failure, repetitive transcranial magnetic stimulation
(rTMS) therapy can be considered. In these case series a combative high frequency
(HF)-rTMS protocol with frequent stimulations at suprathreshold intensity was
applied for treatment-resistant depression (TRD), schizoaffective- and bipolar I
disorder, mixed episode. Besides effectiveness, tolerability was closely
monitored. All three patients, suffering from different psychiatric conditions
were experiencing limited to excellent clinical improvement without serious side
effect or adverse events. These very preliminary results suggest, along with
research using comparable intensive stimulation parameters for
treatment-resistant depression, that ‘aggressively’ targeting the left DLPFC is
well tolerated and safe. Our clinical results suggest a possible beneficial
treatment strategy of HF-rTMS protocols following unsuccessful. Larger
sham-controlled studies are needed to substantiate our results.
PMID: 21057422 [PubMed – indexed for MEDLINE] Neurosci Lett. 2011 Mar 29;492(1):1-4. Epub 2011 Jan 21.

1-Hz low frequency repetitive transcranial magnetic stimulation in children with
Tourette’s syndrome.

Kwon HJ, Lim WS, Lim MH, Lee SJ, Hyun JK, Chae JH, Paik KC.

Environmental Health Center, Department of Preventive Medicine, College of
Medicine, Dankook University, Cheonan, 300714, South Korea.

The aim of the current study was to assess the efficacy of repetitive
transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA)
of the cortex to children with Tourette’s syndrome (TS), if rTMS over the SMA had
positive effects on ameliorating tics. We designed a pilot open label 12 weeks
cohort study to assess the efficacy of rTMS with TS at specific regions. We
administered rTMS over SMA with slow frequency to children with TS. We examined
10 male children (mean age 11.2 ± 2.0 years) diagnosed with TS according to the
Diagnostic and Statistical Manual of Mental Disorders version IV and Schedule for
Affective Disorders and Schizophrenia for School-Age Children-Present and
Lifetime Version. Children with TS were treated with active rTMS to the SMA for
10 daily sessions (1 Hz, 100% of motor threshold, and 1200 stimuli/day). All
subjects completed the study with no side effects and no worsening of ADHD or
depressive and anxiety symptoms. Tic symptoms improved significantly over the 12
weeks of the study. Statistically significant reductions were seen in the Yale
Global Tourette’s Syndrome Severity Scale (YGTSS) and Clinical Global Impression
(CGI). Low-frequency rTMS over the SMA appears to be effective in children with
TS. Further studies using repetitive transcranial magnetic stimulation in TS are
warranted, using blinded, balanced, and parallel designs. rTMS over the SMA to
children with TS might result in a significant clinical improvement and a
normalization of both the hemisphere hyperexcitability.
PMID: 21256925 [PubMed – indexed for MEDLINE] Encephale. 2010 Dec;36 Suppl 6:S197-201.

[Affective disorders and repetitive transcranial magnetic stimulation:
Therapeutic innovations].

[Article in French]

Richieri R, Adida M, Dumas R, Fakra E, Azorin JM, Pringuey D, Lancon C.

Pôle Universitaire de Psychiatrie, Hôpital S(te) Marguerite, 270 bd
Sainte-Marguerite, 13274 Marseille cedex 09, France.

Depression is the most common psychiatric disorder with a particularly important
disability due to its evolution to chronicity and treatment-resistance. In the
same way, the outcome of bipolar disorder is similar. Only 75% subjects remain
remitted in the year following the onset of mood episode and depressive episode
leads to worth responsiveness than patients in phase hypo/manic. Thus, treating
mood episodes and fighting against resistant and residual symptoms or chronicity
of the disorders constitute major clinical issues and economic challenges. They
have generated great interest in finding new non-pharmacological approaches such
as repetitive transcranial magnetic stimulation (rTMS). TMS is a non-invasive
means of focal brain stimulation, rapidly fluctuating magnetic fields. Given the
hypothesis that the right and left sides of the dorsolateral prefrontal cortex
have opposing effects in mood control, high-frequency rTMS activates the left
side and low-frequency to inhibit the right side in the treatment of depression.
A literature review was conducted to study the efficacy of rTMS in the treatment
of unipolar and bipolar depression, acute mania and long-term maintenance
therapy. During the last decade, numerous studies including several meta-analyses
have indicated the efficacy of rTMS in acute treatment of major depressive
disorder. Overall, rTMS seems to be effective in the treatment of bipolar
depression but further trials with larger cohorts should determine optimal
parameters of stimulation. There are also few studies about rTMS in the treatment
of acute mania. Protocols are reversed than in the treatment of depression.
Results are promising but confounded by the presence of concurrent medications.
Finally, the literature on the use of maintenance rTMS in the prevention of
depressive relapse or as a mood stabiliser is limited. Nevertheless it
demonstrates the importance of developing maintenance protocols to maintain the
clinical improvement achieved at the end of the acute treatment. New techniques
to improve the effectiveness of rTMS are already appearing.
PMID: 21237356 [PubMed – indexed for MEDLINE] J ECT. 2011 Mar;27(1):44-7.

The use of topical lidocaine to reduce pain during repetitive transcranial
magnetic stimulation for the treatment of depression.

Trevino K, McClintock SM, Husain MM.

Neurostimulation Laboratory, Department of Psychiatry, University of Texas
Southwestern Medical Center at Dallas, Dallas, TX, USA.

Repetitive transcranial magnetic stimulation (rTMS) is a form of neurostimulation
therapy that was recently approved by the Food and Drug Administration for the
treatment of depression. Repetitive transcranial magnetic stimulation is
considered noninvasive and relatively safe; however, there have been reports of
scalp pain during and at the site of stimulation. This case report documents the
use of topical lidocaine to reduce scalp pain during rTMS administration. All
patients had a diagnosis of major depressive disorder according to research
diagnostic criteria and were washed off antidepressant medications before
treatment. Patients were given active rTMS treatment during a masked, open-label,
or long-term follow-up treatment schedule. Treatment was delivered to the left
dorsolateral prefrontal cortex at 120% of the patient’s observed motor threshold.
Ten patients received 3000 magnetic pulses per session with an on time of 4
seconds and an off time of 26 seconds. Patients who reported pain during
stimulation were given topical lidocaine HCl 2%, which was applied 20 minutes
before treatment. Patients reported mixed outcomes of using topical lidocaine to
reduce scalp pain during stimulation. Half of the patients reported no
significant reduction in pain, whereas the other half indicated a noticeable
decrease during rTMS. As a case report, our study has limited results. Given the
recent approval of rTMS for the treatment of depression, additional studies are
warranted to determine optimal methods of reducing scalp pain.
PMID: 21233765 [PubMed – indexed for MEDLINE] Ann Clin Psychiatry. 2010 Nov;22(4 Suppl 2):S4-11.

Transcranial magnetic stimulation for major depressive disorder: a pragmatic
approach to implementing TMS in a clinical practice.

Derstine T, Lanocha K, Wahlstrom C, Hutton TM.

SunPointe Health, State College, PA, USA.

Another option for managing major depressive disorder (MDD) became available in
October 2008 with the Food and Drug Administration’s (FDA) market clearance of
NeuroStar TMS (transcranial magnetic stimulation) Therapy System. A panel of
psychiatrists who have been treating patients with NeuroStar TMS Therapy in their
clinics assembled for a virtual roundtable discussion regarding their
experiences. In this supplement, the panel addresses the following issues: the
FDA-cleared indication for use of NeuroStar TMS Therapy; logistic and staffing
considerations in the outpatient setting; selecting the right patient for TMS
Therapy; talking with patients and family about TMS Therapy. To give the overview
a meaningful context, each panelist shares a personal account of a patient case,
describing the treatment course and outcomes achieved with TMS Therapy.
PMID: 21180663 [PubMed – indexed for MEDLINE] 13. Psychiatry Clin Neurosci. 2010 Dec;64(6):659-62.

Chronic repetitive transcranial magnetic stimulation failed to change dopamine
synthesis rate: preliminary L-[?-11C]DOPA positron emission tomography study in
patients with depression.

Kuroda Y, Motohashi N, Ito H, Ito S, Takano A, Takahashi H, Nishikawa T, Suhara

Section of Psychiatry and Behavioral Science, Graduate School of Tokyo Medical
and Dental University, Tokyo, Japan.

We have examined the effects of repetitive transcranial magnetic stimulation
(rTMS) on central dopaminergic function in patients with depression using
positron emission tomography with L-[?-11C]DOPA, a ligand to assess the rate of
endogenous dopamine synthesis. Eight patients were treated with 10-daily sessions
of rTMS over the left dorsolateral prefrontal cortex. Positron emission
tomography scanning was performed in each patient twice, before the first session
and 1 day after the last session. Although four out of eight patients responded
to rTMS, there were no changes in the striatal dopamine synthesis rate (k)
following rTMS. These results suggest that chronic rTMS had a limited effect on
the dopaminergic system.
PMID: 21155169 [PubMed – indexed for MEDLINE] Conf Proc IEEE Eng Med Biol Soc. 2010;2010:581-4.

Modeling of electromagnetic stimulation of the human brain.

Lazutkin D, Husar P.

Division of Biological Signal Processing, Department of Biomedical Engineering
and Medical Informatics, Ilmenau University of Technology, PO Box 100565, 98684,
Germany. dmitry.lazutkin@tu-ilmenau.de

The World Health Organization estimates depression as a serious threat to the
health of millions of people worldwide. The purpose of this paper is to introduce
the ongoing research devoted to the investigation of a possibility to use
low-field electromagnetic stimulation of the human brain in the treatment of
depressive disorder. In the course of the work the 3D models of transcranial
magnetic stimulation and low-field magnetic stimulation based upon the use of a
layered sphere head model have been developed. An initial approach towards the
realistic human head reconstruction has been made. The revealed order of the
stimulating electromagnetic field suitable for operation makes it possible to
draft a technical specification for the stimulation device.
PMID: 21095888 [PubMed – indexed for MEDLINE] J Affect Disord. 2011 Apr;130(1-2):312-7. Epub 2010 Nov 5.

High frequency repetitive transcranial magnetic stimulation as an augmenting
strategy in severe treatment-resistant major depression: a prospective 4-week
naturalistic trial.

Berlim MT, McGirr A, Beaulieu MM, Turecki G.

Depressive Disorders Program, Douglas Mental Health University Institute and
McGill University, Montréal, Québec, Canada. mtberlim@gmail.com

BACKGROUND: Randomized, controlled trials (RCTs) have found repetitive
transcranial magnetic stimulation (rTMS) to be effective for major depression,
but its usefulness as an augmenting strategy for severe treatment-resistant
depression (TRD) has yet to be firmly established.
METHODS: In a naturalistic trial, 15 chronically depressed, severely
treatment-resistant patients were treated with daily high frequency (HF) rTMS
over the left dorsolateral prefrontal cortex (DLPFC) for 4 weeks as an augmenting
strategy. Depressive and anxious symptoms (both subjective and objective), as
well as quality of life (QOL) domains were measured pre-post rTMS treatment.
RESULTS: Pre-post rTMS comparisons revealed significant reductions of both
clinician-rated and selfreport depression and anxiety measures and increases in
three (out of five) domains of subjective QOL (i.e., global, physical, and
LIMITATIONS: Small sample size and non-controlled design.
CONCLUSIONS: Our results suggest that HF rTMS, when used as an augmenting
strategy, positively affects depressive and anxious symptoms as well as QOL in
patients with severe TRD. However, further studies with larger samples and
controlled designs are needed to better clarify our preliminary findings.
PMID: 21056475 [PubMed – indexed for MEDLINE] Ther Umsch. 2010 Nov;67(11):585-91.

[Biological treatment strategies of depression–psychopharmacology and
non-pharmacological methods].

[Article in German]

Hatzinger M.

Erwachsenenpsychiatrie, Psychiatrische Dienste der Solothurner Spitäler AG.

Biological treatment procedures are based on evidence-based guidelines. According
to all of them, a correct diagnosis of depression is required before starting
therapy. Within recent years many different types of antidepressants have been
introduced to the pharmacotherapeutic armamentarium. The “newer” antidepressants
were developed with a view to reduced side effects. However, the classes of
antidepressants currently available differ little in their antidepressant
efficacy, thus, all producing treatment responses of 50 – 75 %. Therefore, the
selection of a particular antidepressant for the individual patient depends on
various factors: patient’s prior experience with medication, concurrent medical
conditions that may be worsened by selected antidepressants, concomitant use of
non-psychiatric medications that may lead to negative drug-drug interactions, a
drug’s short and long-term side effects, physician’s experience with the
medication and patient’s history of adherence to medication. Importantly, if the
patient does not show any improvement after two to four weeks of treatment with
an antidepressant dose at the upper level of the standard dose, it becomes less
likely that he will respond to this particular medication later. When a partial
or non-response is present, several therapeutic options are available: (1)
combining two antidepressants from different classes, (2) switch to new
antidepressant from a different or the same pharmacological class and (3)
augmentation strategies. For patients who are reluctant to take traditional
antidepressants, herbal remedies such as hypericum perforatum (St. John’s Wort)
provide an alternative for treatment of mild to moderate depression. Besides
pharmacological treatment options non pharmacological biological interventions
are available. Electroconvulsive therapy and partial sleep deprivation are very
effective in the treatment of acute depression. Especially for seasonal affective
disorders light therapy is a well established treatment alternative. Further new
biological treatment approaches such as rapid transcranial magnetic stimulation
(rTMS) showed inconsistent results.
PMID: 21043020 [PubMed – indexed for MEDLINE] Expert Rev Neurother. 2010 Nov;10(11):1761-72.

Transcranial magnetic stimulation for the treatment of depression.

George MS.

Institute of Psychiatry, Medical University of South Carolina, 502 N, 67
President St, Charleston, SC 29425, USA. georgem@musc.edu

Repeated daily left prefrontal transcranial magnetic stimulation (TMS) was first
proposed as a potential treatment for depression in 1993. Multiple studies from
researchers around the world since then have repeatedly demonstrated that TMS has
antidepressant effects greater than sham treatment, and that these effects are
clinically meaningful. A large industry-sponsored trial, published in 2007,
resulted in US FDA approval in October 2008. Most recently, a large NIH-sponsored
trial, with a more rigorous sham technique, found that a course of treatment (3-5
weeks) was statistically and clinically significant in reducing depression.
However, consistently showing statistically and clinically significant
antidepressant effects, and gaining regulatory approval, is merely the beginning
for this new treatment. As with any new treatment involving a radically different
approach, there are many unanswered questions about TMS, and the field is still
rapidly evolving. These unanswered questions include the appropriate scalp
location, understanding the mechanisms of action, refining the ‘dose’ (frequency,
train, number of stimuli/day and pattern of delivery), understanding whether and
how TMS can be combined with medications or talking/exposure therapy, or both,
and how to deliver maintenance TMS. This article summarizes the available
clinical information, and discusses key areas where more research is needed. TMS
reflects a paradigm shift in treating depression. It is a safe, relatively
noninvasive, focal brain stimulation treatment that does not involve seizures or
implanted wires, and does not have drug-drug interactions or systemic side
PMID: 20977332 [PubMed – indexed for MEDLINE] Actas Esp Psiquiatr. 2010 Mar;38(2):87-93. Epub 2010 Mar 1.

Efficacy of transcranial magnetic stimulation (TMS) in depression: naturalistic

Aliño JJ, Jiménez JL, Flores SC, Alcocer MI.

Psychiatry Department, Hospital Clínico San Carlos, Madrid. jli@lopezibor.com

Transcranial magnetic stimulation (TMS) is a technique is which the evidence has
been confirming its efficacy. Repetitive stimulation (rTMS) of the left
prefrontal dorsolateral (LPFDL) area with frequencies between 10 and 20 Hz has
been shown to be effective in major depression. This article presents the
prospective analysis of the treatments performed using TMS on LPFDL at 20 Hz with
an intensity of 70% in a protocol of 10 sessions on 107 patients (41 male and 61
female) due to drug treatment resistant depressive symptoms in different
conditions. The patients had previously undergone two psychopharmacological
attempts with adequate dosage and time, who had been considered candidates for
electroconvulsive therapy (ECT) if they did not respond to any conventional
treatment. A total of 62.7% had mood disorder, 13.1% obsessive-compulsive
disorders (OCT), 7.5% cognitive disorders, 4.7% personality disorders and 3.7%
were psychiatric disorders. Mean age of the group was 49.98 years (SD = 17.09).
The global results showed that the TMS provided some degree of improvement in
48.6%, although only half, that is 24.3%, maintained it beyond week 12. Efficacy
by diagnoses showed a significant difference in favor of affective disorders. In
the case of bipolar disorders in the depressive phase, there was improvement in
88.9%, which was maintained in 66.7% of the patients treated. No differences in
efficacy were found within each one of the groups diagnosed based on gender, age
or presence of personality disorders. The efficacy of the ECT was similar to the
TMS in the group in which it had to be applied in comparison with the general
group. New studies are proposed with the inclusion of the TMS for
resistant-depression treatment protocols in a step prior to the ECT and even
before all the drug treatments had been attempted, combining it with them for
their potentiation.
PMID: 20976637 [PubMed – indexed for MEDLINE] J ECT. 2011 Mar;27(1):11-7.

High-frequency prefrontal repetitive transcranial magnetic stimulation for the
negative symptoms of schizophrenia: a case series.

Stanford AD, Corcoran C, Bulow P, Bellovin-Weiss S, Malaspina D, Lisanby SH.

Division of Brain Stimulation and Therapeutic Modulation, New York State
Psychiatric Institute, New York, NY, USA. as1019@columbia.edu

OBJECTIVES: The negative symptoms of schizophrenia are difficult to treat and are
predictors of poor outcome. New somatic treatments are needed to reverse these
symptoms and improve function. One promising approach is repetitive transcranial
magnetic stimulation (rTMS), although results to date have been mixed. This pilot
study assessed higher doses of rTMS and assessed particular demographic factors
that may influence treatment response.
METHODS: Five patients with schizophrenia or schizoaffective disorder enrolled to
receive 20 sessions of rTMS administered with a Magstim Super Rapid device (The
Magstim Company Ltd, Wales, UK). Treatment was administered at 20 Hz for 2
seconds, intertrain interval of 28 seconds, and at 100% motor threshold to the
left dorsolateral prefrontal cortex in an open-label pilot study. Positive and
Negative Syndrome Scale symptom assessments occurred at 2-week intervals during
treatment and twice at 4-week intervals after termination.
RESULTS: Treatments were well tolerated with no adverse events. One patient
withdrew from the study in the setting of medication noncompliance. Of the
patients who completed treatment, 2 had reductions in positive symptoms by 9% and
26%, maintained at 1 month. A third patient had a 14% reduction in negative
symptoms at week 4, and a fourth patient had a 55% reduction at week 4. Negative
symptom improvement was not related to depressive or extrapyramidal symptoms,
which were unchanged with treatment.
CONCLUSIONS: This pilot study of rTMS treatment for the negative symptoms of
schizophrenia is promising with respect to safety and feasibility. The promising
preliminary evidence for improvements in this open-label setting should be
followed up with a randomized clinical trial to establish efficacy. Further work
may explore the potential utility of rTMS for the otherwise largely untreatable
negative symptoms, which account for so much of the morbidity of schizophrenia.
PMCID: PMC3042491 [Available on 2012/3/1] PMID: 20966771 [PubMed – indexed for MEDLINE] Brain Stimul. 2010 Oct;3(4):211-7. Epub 2009 Dec 30.

Response to deep TMS in depressive patients with previous electroconvulsive

Rosenberg O, Zangen A, Stryjer R, Kotler M, Dannon PN.

The Beer Ya’acov Mental Health Institution, Beer Ya’acov, Israel.

BACKGROUND: The efficacy of transcranial magnetic stimulation (TMS) in the
treatment of major depression has already been shown. Novel TMS coils allowing
stimulation of deeper brain regions have recently been developed and studied.
OBJECTIVE: Our study is aimed at exploring the possible efficacy of deep TMS in
patients with resistant depression, who previously underwent electroconvalsive
therapy (ECT).
METHODS: Using Brainsway’s deep TMS H1 coil, six patients who previously
underwent ECT, were treated with 120% power of the motor threshold at a frequency
of 20 Hz. Patients underwent five sessions per week, up to 4 weeks. Before the
study, patients were evaluated using the Hamilton depression rating scale (HDRS,
24 items), the Hamilton anxiety scale, and the Beck depression inventory and were
again evaluated after 5, 10, 15, and 20 daily treatments. Response to treatment
was considered a reduction in the HDRS of at least 50%, and remission was
considered a reduction of the HDRS-24 below 10 points.
RESULTS: Two of six patients responded to the treatment with deep TMS, including
one who achieved full remission.
CONCLUSIONS: Our results suggest the possibility of a subpopulation of depressed
patients who may benefit from deep TMS treatment, including patients who did not
respond to ECT previously. However, the power of the study is small and similar
larger samples are needed.
PMID: 20965450 [PubMed – indexed for MEDLINE] Brain Stimul. 2010 Oct;3(4):200-6. Epub 2010 Jun 29.

Can a behavioral intervention enhance the effect of repetitive transcranial
magnetic stimulation on mood?

Hoy KE, Enticott PG, Daskalakis ZJ, Fitzgerald PB.

Monash Alfred Psychiatry Research Centre, The Alfred and Monash University School
of Psychology and Psychiatry, Victoria, Australia. Kate.Hoy@med.monash.edu.au

BACKGROUND: One of the few novel treatments developed for major depression in
recent years has been repetitive transcranial magnetic stimulation (rTMS).
Despite mostly promising results, 50-60% of patients do not respond to rTMS.
Therefore, it is important to investigate ways of enhancing the effectiveness of
this treatment. To date, attempting to enhance the mood effects of rTMS via
behavioral means has not been investigated. One such intervention involves
concurrent exposure to affective stimuli that have been shown to result in
activation of brain regions associated with emotion. This pilot study of ten
participants investigates such an intervention.
OBJECTIVES: The aim of this pilot study was to investigate whether exposing
participants to affective stimuli while they were receiving 5 Hz rTMS resulted in
greater mood change compared with rTMS or affective stimuli alone.
METHODS: Ten healthy male and female participants were exposed to affective
stimuli while receiving rTMS. All participants took part in three counterbalanced
conditions conducted a week apart in which they received rTMS (active or sham)
delivered to the left dorsolateral prefrontal cortex (DLPFC) combined with
affective stimuli (positive or neutral). To measure the impact of the dual
intervention visual analogue mood scales and an affective go no go task were
conducted pre- and post intervention for each session.
RESULTS: There was no effect of any rTMS condition on performances on the
affective go no go task, or on any of the visual analogue scales.
CONCLUSIONS: The current data do not provide support for the use of affective
stimuli during rTMS. Methodological limitations that may have contributed to the
lack of significant findings are discussed.
PMID: 20965448 [PubMed – indexed for MEDLINE] Brain Stimul. 2010 Oct;3(4):187-99. Epub 2010 Aug 11.

Durability of clinical benefit with transcranial magnetic stimulation (TMS) in
the treatment of pharmacoresistant major depression: assessment of relapse during
a 6-month, multisite, open-label study.

Janicak PG, Nahas Z, Lisanby SH, Solvason HB, Sampson SM, McDonald WM, Marangell
LB, Rosenquist P, McCall WV, Kimball J, O’Reardon JP, Loo C, Husain MH, Krystal
A, Gilmer W, Dowd SM, Demitrack MA, Schatzberg AF.

Department of Psychiatry, Rush University Medical Center, Chicago, Illinois
60612, USA. pjanicak@rush.edu

BACKGROUND: Although transcranial magnetic stimulation (TMS) can be an effective
acute antidepressant treatment, few studies systematically examine persistence of
OBJECTIVE: We assessed the durability of antidepressant effect after acute
response to TMS in patients with major depressive disorder (MDD) using
protocol-specified maintenance antidepressant monotherapy.
METHODS: Three hundred one patients were randomly assigned to active or sham TMS
in a 6-week, controlled trial. Nonresponders could enroll in a second, 6-week,
open-label study. Patients who met criteria for partial response (i.e., >25%
decrease from the baseline HAMD 17) during either the sham-controlled or
open-label study (n = 142) were tapered off TMS over 3 weeks, while
simultaneously starting maintenance antidepressant monotherapy. Patients were
then followed for 24 weeks in a naturalistic follow-up study examining the
long-term durability of TMS. During this durability study, TMS was readministered
if patients met prespecified criteria for symptom worsening (i.e., a change of at
least one point on the CGI-S scale for 2 consecutive weeks). Relapse was the
primary outcome measure.
RESULTS: Ten of 99 (10%; Kaplan-Meier survival estimate = 12.9%) patients
relapsed. Thirty-eight (38.4%) patients met criteria for symptom worsening and
32/38 (84.2%) reachieved symptomatic benefit with adjunctive TMS. Safety and
tolerability were similar to acute TMS monotherapy.
CONCLUSIONS: These initial data suggest that the therapeutic effects of TMS are
durable and that TMS may be successfully used as an intermittent rescue strategy
to preclude impending relapse.
PMID: 20965447 [PubMed – indexed for MEDLINE] Neurosci Biobehav Rev. 2011 Jan;35(3):818-25. Epub 2010 Oct 12.

Evidence for GABAergic inhibitory deficits in major depressive disorder.

Croarkin PE, Levinson AJ, Daskalakis ZJ.

Department of Psychiatry, UT Southwestern Medical Center Dallas, 6300 Harry Hines
Boulevard, Suite 1200, Dallas, TX 75390-8589, USA.

Converging evidence suggests that deficits in gamma-aminobutyric acid (GABA)
functioning are implicated in the pathophysiology of major depressive disorder
(MDD). This is highlighted by research investigating cortical inhibition (CI), a
process whereby GABAergic interneurons selectively attenuate pyramidal neurons.
Transcranial magnetic stimulation (TMS) paradigms evaluate this marker of
neuronal inhibitory activity in the cortex. This review will examine the
neuroanatomic and neurophysiological evidence from neuroimaging, molecular,
treatment, and TMS studies linking dysfunctional GABAergic neurotransmission to
PMID: 20946914 [PubMed – indexed for MEDLINE] J Affect Disord. 2011 Mar;129(1-3):385-90. Epub 2010 Sep 22.

A survey of patient acceptability of repetitive transcranial magnetic stimulation
(TMS) during pregnancy.

Kim DR, Sockol L, Barber JP, Moseley M, Lamprou L, Rickels K, O’Reardon JP,
Epperson CN.

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104,
United States. drkim@mail.med.upenn.edu

OBJECTIVE: Given the data that depression is common during pregnancy and that
pregnant women prefer non-medication treatment options, we hypothesize repetitive
transcranial magnetic stimulation (TMS) may be a treatment option. Given the
novelty of TMS, we sought to assess whether patient acceptability would be a
barrier to enrolling pregnant women in TMS studies.
METHODS: In Study 1, 500 pregnant women were surveyed in an outpatient, urban
obstetrics clinic using the Edinburgh Depression Rating Scale (EPDS) and a
treatment acceptability survey. In Study 2, 51 women were surveyed with the EPDS
and acceptability survey using an informational video to increase participant
knowledge about TMS.
RESULTS: Approximately 25% of participants had an EPDS score of ?12 in both
studies. Psychotherapy was identified as the most acceptable treatment option.
TMS was considered an unacceptable treatment option to virtually all women before
the informational video. After the video, 15.7% considered TMS an acceptable
treatment option.
CONCLUSION: Psychotherapy is the most acceptable treatment option for depression
to pregnant women. Increasing participant knowledge about TMS increased its
acceptability significantly. Large-scale multi-center trials are needed for
confirmation of these results.
PMID: 20864179 [PubMed – indexed for MEDLINE] Arq Neuropsiquiatr. 2010 Jun;68(3):433-51.

Neuromodulation approaches for the treatment of major depression: challenges and
recommendations from a working group meeting.

Brunoni AR, Teng CT, Correa C, Imamura M, Brasil-Neto JP, Boechat R, Rosa M,
Caramelli P, Cohen R, Del Porto JA, Boggio PS, Fregni F.

Department and Institute of Psychiatry, University of São Paulo, São Paulo, SP,

The use of neuromodulation as a treatment for major depressive disorder (MDD) has
recently attracted renewed interest due to development of other
non-pharmacological therapies besides electroconvulsive therapy (ECT) such as
transcranial magnetic stimulation (TMS), transcranial direct current stimulation
(tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS).METHOD:
We convened a working group of researchers to discuss the updates and key
challenges of neuromodulation use for the treatment of MDD.
RESULTS: The state-of-art of neuromodulation techniques was reviewed and
discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a
comprehensive overview of the neuromodulation techniques; [3] using
neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome
DISCUSSION: ECT is the first-line treatment for severe depression. TMS and tDCS
are strategies with a relative benign profile of side effects; however, while TMS
effects are comparable to antidepressant drugs for treating MDD; further research
is needed to establish the role of tDCS. DBS and VNS are invasive strategies with
a possible role in treatment-resistant depression. In summary, MDD is a chronic
and incapacitating condition with a high prevalence; therefore clinicians should
consider all the treatment options including invasive and non-invasive
neuromodulation approaches.

PMID: 20602051 [PubMed – indexed for MEDLINE] CNS Drugs. 2010 Feb 1;24(2):131-61. doi: 10.2165/11530280-000000000-00000.

Therapeutic options for treatment-resistant depression.

Shelton RC, Osuntokun O, Heinloth AN, Corya SA.

Department of Psychiatry, Vanderbilt University School of Medicine, Nashville,
Tennessee, USA.

Treatment-resistant depression (TRD) presents major challenges for both patients
and clinicians. There is no universally accepted definition of TRD, but results
from the US National Institute of Mental Health’s (NIMH) STAR*D (Sequenced
Treatment Alternatives to Relieve Depression) programme indicate that after the
failure of two treatment trials, the chances of remission decrease significantly.
Several pharmacological and nonpharmacological treatments for TRD may be
considered when optimized (adequate dose and duration) therapy has not produced a
successful outcome and a patient is classified as resistant to treatment.
Nonpharmacological strategies include psychotherapy (often in conjunction with
pharmacotherapy), electroconvulsive therapy and vagus nerve stimulation. The US
FDA recently approved vagus nerve stimulation as adjunctive therapy (after four
prior treatment failures); however, its benefits are seen only after prolonged
(up to 1 year) use. Other nonpharmacological options, such as repetitive
transcranial stimulation, deep brain stimulation or psychosurgery, remain
experimental and are not widely available. Pharmacological treatments of TRD can
be grouped in two main categories: ‘switching’ or ‘combining’. In the first,
treatment is switched within and between classes of compounds. The benefits of
switching include avoidance of polypharmacy, a narrower range of
treatment-emergent adverse events and lower costs. An inherent disadvantage of
any switching strategy is that partial treatment responses resulting from the
initial treatment might be lost by its discontinuation in favour of another
medication trial. Monotherapy switches have also been shown to have limited
effectiveness in achieving remission. The advantage of combination strategies is
the potential to build upon achieved improvements; they are generally recommended
if partial response was achieved with the current treatment trial. Various
non-antidepressant augmenting agents, such as lithium and thyroid hormones, are
well studied, although not commonly used. There is also evidence of efficacy and
increasing use of atypical antipsychotics in combination with antidepressants,
for example, olanzapine in combination with fluoxetine (OFC) or augmentation with
aripiprazole. The disadvantages of a combination strategy include multiple
medications, a broader range of treatment-emergent adverse events and higher
costs. Several experimental pharmaceutical treatment alternatives for TRD are
also being explored in combination with antidepressants or as monotherapy. These
less studied alternative compounds include pindolol, inositol, CNS stimulants,
hormones, herbal supplements, omega-3 fatty acids, S-adenosyl-L-methionine, folic
acid, lamotrigine, modafinil, riluzole and topiramate. In summary, despite an
increasing variety of choices for the treatment of TRD, this condition remains
universally undefined and represents an area of unmet medical need. There are few
known approved pharmacological agents for TRD (aripiprazole and OFC) and overall
outcomes remain poor. This might be an indication that depression itself is a
heterogeneous condition with a great diversity of pathologies, highlighting the
need for careful evaluation of individuals with depressive symptoms who are
unresponsive to treatment. Clearly, more research is needed to provide clinicians
with better guidance in making those treatment decisions–especially in light of
accumulating evidence that the longer patients are unsuccessfully treated, the
worse their long-term prognosis tends to be.

PMID: 20088620 [PubMed – indexed for MEDLINE] Acta Neurochir (Wien). 2010 Apr;152(4):565-77. Epub 2010 Jan 26.

Neurostimulatory and ablative treatment options in major depressive disorder: a
systematic review.

Andrade P, Noblesse LH, Temel Y, Ackermans L, Lim LW, Steinbusch HW,
Visser-Vandewalle V.

Department of Neuroscience, Faculty of Health, Medicine and Life Sciences,
Maastricht University, 6200 MD Maastricht, The Netherlands.

INTRODUCTION: Major depressive disorder is one of the most disabling and common
diagnoses amongst psychiatric disorders, with a current worldwide prevalence of
5-10% of the general population and up to 20-25% for the lifetime period.
HISTORICAL PERSPECTIVE: Nowadays, conventional treatment includes psychotherapy
and pharmacotherapy; however, more than 60% of the treated patients respond
unsatisfactorily, and almost one fifth becomes refractory to these therapies at
long-term follow-up. NONPHARMACOLOGICAL TECHNIQUES: Growing social incapacity and
economic burdens make the medical community strive for better therapies, with
fewer complications. Various nonpharmacological techniques like electroconvulsive
therapy, vagus nerve stimulation, transcranial magnetic stimulation, lesion
surgery, and deep brain stimulation have been developed for this purpose.
DISCUSSION: We reviewed the literature from the beginning of the twentieth
century until July 2009 and described the early clinical effects and main
reported complications of these methods.
PMCID: PMC2844529
PMID: 20101419 [PubMed – indexed for MEDLINE] 4. Restor Neurol Neurosci. 2010;28(4):577-86.

Influence of repetitive transcranial magnetic stimulation on special symptoms in
depressed patients.

Höppner J, Berger C, Walter U, Padberg F, Buchmann J, Herwig U, Domes G.

Department of Psychiatry and Psychotherapy, Centre of Nervous Disease, University
of Rostock, Rostock, Germany. jacqueline.hoeppner@med.unirostock.de

Since various studies, including multi-centre studies, investigating the effect
of repetitive transcranial magnetic stimulation (rTMS) in depression have shown
different results, it is now important to research, which symptoms of depression
are most responsive to this kind of non-invasive brain stimulation. Furthermore,
an increasing interest of rTMS as a potential tool for treatment of neurological
and psychiatric disorders should be recorded. Therefore, it is critical to
investigate dopaminergic functional interactions in the prefrontal cortex, and in
particular, the effect of dorsolateral prefrontal cortex stimulation on clinical
symptoms depending on dopaminergic concentrations in various brain regions. This
short review summarizes important preliminary data, which focus on the
symptom-oriented effects of rTMS in depression.

PMID: 20714080 [PubMed – indexed for MEDLINE] Exp Neurol. 2009 Sep;219(1):2-13. Epub 2009 May 4.

Repetitive transcranial magnetic stimulation of the prefrontal cortex in

Padberg F, George MS.

Department of Psychiatry, Ludwig-Maximilian University, Nussbaumstr. 7, 80336
Munich, Germany. padberg@med.uni-muenchen.de

Transcranial magnetic stimulation is an interesting technique for non-invasively
stimulating the brain in awake alert humans. It is a powerful research tool for
examining brain behavior relationships. Additionally many researchers are
investigating whether repeatedly applying TMS to specific regions over several
days to weeks might have therapeutic effects. By far the largest amount of work
has been done investigating whether daily applications of prefrontal TMS can
improve the symptoms of major depression. We review the literature combining TMS
with brain imaging, and then overview the clinical work done to date with TMS in
depression. The literature to date suggests that daily prefrontal TMS for several
weeks clearly has antidepressant effects, but much work remains to establish the
effect sizes and improve the methods of delivery in order to improve its
potential clinical utility.

PMID: 19409383 [PubMed – indexed for MEDLINE] J Affect Disord. 2009 Oct;117(3):137-45. Epub 2009 Feb 7.

Transcranial direct current stimulation: a new tool for the treatment of

Arul-Anandam AP, Loo C.

School of Psychiatry, University of New South Wales, Sydney, Australia.

Transcranial direct current stimulation (tDCS) is a non-invasive brain
stimulation technique that applies mild (typically 1-2 mA) direct currents via
the scalp to enhance or diminish neuronal excitability. The technique has a dual
function: on the one hand, it has been used to investigate the functions of
various cortical regions; on the other, it has been used as an experimental
treatment modality, most notably for Major Depressive Disorder (MDD). With the
growing utility of tDCS in psychiatry, it is important from the vantage of safety
and effectiveness to understand its underlying neurobiological mechanisms. In
this respect, researchers have made significant progress in recent years,
highlighting changes in resting membrane potential, spontaneous neuronal firing
rates, synaptic strength, cerebral blood flow and metabolism subsequent to tDCS.
We briefly review tDCS clinical trials for MDD, and then consider its mechanisms
of action, identifying potential avenues for future research.
PMID: 19201483 [PubMed – indexed for MEDLINE] Recent Pat CNS Drug Discov. 2009 Jun;4(2):149-59.

Mood disorders in elderly population: neurostimulative treatment possibilities.

Rosenberg O, Shoenfeld N, Kotler M, Dannon PN.

Brain Stimulation Unit, Beer Ya’acov Mental Health Center, Israel.

Treatment of mood disorders is one of the most challenging territories in
elderly. Effectiveness of different treatment strategies could be related to age,
sex and physical conditions. The side effect profile in this population also
affects pharmacological interventions. Our review includes the neurostimulative
treatment strategies in elderly. However, possible treatment strategies such as
electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus
nerve stimulation (VNS) and deep brain stimulation (DBS) were less studied in
elderly. ECT was found to be an effective treatment procedure in mood disorders.
Few double-blind sham controlled studies were conducted and demonstrated
effectiveness of TMS. DBS has lack of double-blind studies. ECT seems to be the
golden standard for the treatment resistant elderly patients, yet side effect
profile of ECT in elderly will be discussed. Double -blind sham controlled
studies with larger samples are necessary to confirm preliminary results with
transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST)
and VNS, DBS.

PMID: 19519563 [PubMed – indexed for MEDLINE] Brain Stimul. 2009 Jan;2(1):14-21. Epub 2008 Jun 27.

Controversy: Repetitive transcranial magnetic stimulation or transcranial direct
current stimulation shows efficacy in treating psychiatric diseases (depression,
mania, schizophrenia, obsessive-complusive disorder, panic, posttraumatic stress

George MS, Padberg F, Schlaepfer TE, O’Reardon JP, Fitzgerald PB, Nahas ZH,
Marcolin MA.

Psychiatry Department, Medical University of South Carolina, Charleston, 29425,
USA. georgem@musc.edu

Brain imaging studies performed over the past 20 years have generated new
knowledge about the specific brain regions involved in the brain diseases that
have been classically labeled as psychiatric. These include the mood and anxiety
disorders, and the schizophrenias. As a natural next step, clinical researchers
have investigated whether the minimally invasive brain stimulation technologies
(transcranial magnetic stimulation [TMS] or transcranial direct current
stimulation [tDCS]) might potentially treat these disorders. In this review, we
critically review the research studies that have examined TMS or tDCS as putative
treatments for depression, mania, obsessive-complusive disorder, posttraumatic
stress disorder, panic disorder, or schizophrenia. (Separate controversy articles
deal with using TMS or tDCS to treat pain or tinnitus. We will not review here
the large number of studies using TMS or tDCS as research probes to understand
disease mechanisms of psychiatric disorders.) Although there is an extensive body
of randomized controlled trials showing antidepressant effects of daily
prefrontal repetitive TMS, the magnitude or durability of this effect remains
controversial. US Food and Drug Administration approval of TMS for depression was
recently granted. There is much less data in all other diseases, and therapeutic
effects in other psychiatric conditions, if any, are still controversial. Several
issues and problems extend across all psychiatric TMS studies, including the
optimal method for a sham control, appropriate coil location, best device
parameters (intensity, frequency, dosage, and dosing schedule) and refining what
subjects should be doing during treatment (activating pathologic circuits or
not). In general, TMS or tDCS as a treatment for most psychiatric disorders
remains exciting but controversial, other than prefrontal TMS for depression.

PMID: 20633399 [PubMed – indexed for MEDLINE] Curr Psychiatry Rep. 2009 Dec;11(6):447-52.

Transcranial magnetic stimulation in the treatment of psychiatric disorders.

Kim DR, Pesiridou A, O’Reardon JP.

Perinatal Psychiatry Clinic, Department of Psychiatry, University of
Pennsylvania, 3535 Market Street, 2nd Floor, Philadelphia, PA 19104, USA.

Transcranial magnetic stimulation (TMS) is an emerging novel treatment modality
for psychiatric disorders, particularly major depression. A device for delivery
of TMS was approved by the US Food and Drug Administration for treatment of major
depressive disorder in adults. TMS is being studied for a variety of psychiatric
disorders, including obsessive-compulsive disorder, post-traumatic stress
disorder, and auditory hallucinations in schizophrenia. In this article, we
describe TMS and its neurobiologic basis, as well as the efficacy and safety data
of TMS with regard to a range of psychiatric disorders.

PMID: 19909666 [PubMed – indexed for MEDLINE] Can J Psychiatry. 2008 Sep;53(9):621-31.

Repetitive transcranial magnetic stimulation for treatment-resistant depression:
a systematic review and metaanalysis.

Lam RW, Chan P, Wilkins-Ho M, Yatham LN.

Division of Clinical Neuroscience, Department of Psychiatry, University of
British Columbia, Vancouver, British Columbia. r.lam@ubc.ca

OBJECTIVE: Systematic reviews show that repetitive transcranial magnetic
stimulation (rTMS) is superior to sham control conditions in patients with major
depressive disorder, but the clinical relevance is not clear. None have
specifically examined outcomes in patients with treatment-resistant depression
METHOD: A systematic review was conducted by identifying published randomized
controlled trials of active rTMS, compared with a sham control condition in
patients with defined TRD (that is, at least one failed trial). The primary
outcome was clinical response as determined from global ratings, or 50% or
greater improvement on a rating scale. Other outcomes included remission and
standardized mean differences in end point scores. Metaanalysis was conducted for
absolute risk differences using random effects models. Sensitivity and subgroup
analyses were also conducted to explore heterogeneity and robustness of results.
RESULTS: A total of 24 studies (n = 1092 patients) met criteria for quantitative
synthesis. Active rTMS was significantly superior to sham conditions in producing
clinical response, with a risk difference of 17% and a number-needed-to-treat of
6. The pooled response and remission rates were 25% and 17%, and 9% and 6% for
active rTMS and sham conditions, respectively. Sensitivity and subgroup analyses
did not significantly affect these results. Dropouts and withdrawals owing to
adverse events were very low.
CONCLUSIONS: For patients with TRD, rTMS appears to provide significant benefits
in short-term treatment studies. However, the relatively low response and
remission rates, the short durations of treatment, and the relative lack of
systematic follow-up studies suggest that further studies are needed before rTMS
can be considered as a first-line monotherapy treatment for TRD.

PMID: 18801225 [PubMed – indexed for MEDLINE] Can J Psychiatry. 2008 Sep;53(9):555-66.

Repetitive transcranial magnetic stimulation for major depressive disorder: a

Daskalakis ZJ, Levinson AJ, Fitzgerald PB.

Schizophrenia Program, Centre for Addiction and Mental Health, University of
Toronto, Toronto, Ontario. jeff_daskalakis@camh.net

Comment in:
Can J Psychiatry. 2008 Sep;53(9):553-4.

Several studies demonstrated that repetitive transcranial magnetic stimulation
(rTMS) is an efficacious treatment for treatment-resistant major depressive
disorder (TRD). Recent metaanalyses and more recent large multicentre studies
provided evidence suggesting that rTMS is indeed a promising treatment; however,
its efficacy has often been shown to be modest, compared with sham stimulation.
We review these lines of evidence and discuss several reasons that may explain
the modest therapeutic efficacy in most of these studies, including: most
involved left-sided treatment alone to the dorsolateral prefrontal cortex (DLPFC)
only, which may be less optimal than applying bilateral stimulation; suboptimal
methods were used to target the DLPFC (that is, the 5-cm anterior method),
limiting the treatment potential of inherently a targeted form of treatment; some
treatment durations were short (that is, 2 to 4 weeks); and stimulation intensity
might have been insufficient by not considering coil-to-cortex distance, which
has been linked to rTMS-induced antidepressant response. Future studies
attempting to address the above-mentioned limitations are necessary to
potentially optimize the efficacy of this already promising treatment option in
TRD. Finally, it is also essential that research investigate the mechanisms of
therapeutic efficacy, thus increases in understanding can be translated into
enhanced treatment. For several reasons that will be reviewed, cortical
excitability may represent an important mechanism, linked to the therapeutic
efficacy of this disorder.

PMID: 18801218 [PubMed – indexed for MEDLINE] Curr Opin Psychiatry. 2008 Nov;21(6):640-4.

Transcranial magnetic stimulation.

López-Ibor JJ, López-Ibor MI, Pastrana JI.

Department of Psychiatry, Complutense University, Madrid, Spain.

PURPOSE OF REVIEW: To present state-of-the-art transcranial magnetic stimulation
(TMS) therapy, especially when it is used in psychiatric disorders, on the basis
of an exhaustive literature search from 2006 to date (June 2008) on TMS papers
published in Medline and Embase. Other references and comments from our own
experience started 8 years ago have also been taken into account.
RECENT FINDINGS: The mechanism of action of TMS is now better understood. There
is strong evidence of the safety and tolerability of TMS when standard protocols
are used. The efficacy of the stimulation of the dorsolateral prefrontal cortex
in depression is well documented, and there is evidence of the utility of TMS in
posttraumatic stress disorder, in persistent auditory hallucinations in
schizophrenia and in attention-deficit disorder with hyperactivity.
SUMMARY: There is enough evidence of the efficacy and safety of TMS in depression
to include this technique in the therapeutic protocols of major depression.
However, more research is needed on the use of this technique in other
psychiatric and nonpsychiatric disorders such as posttraumatic stress disorder,
persistent auditory hallucinations, attention-deficit disorder with hyperactivity
and tinnitus.

PMID: 18852574 [PubMed – indexed for MEDLINE] Presse Med. 2008 May;37(5 Pt 2):877-82. Epub 2008 Mar 19.

[Non-drug treatment for depression].

[Article in French]

Bottai T.

Service de psychiatrie générale de Martigues 13G24, Hôpital du Vallon, F-13698
Martigues, France. thierry.bottai@ch-martigues.fr

The principal alternatives to pharmacological treatment of major depressive
disorder (besides electroconvulsive therapy) are different forms of
psychotherapy, frequently used in combination with antidepressant drugs. The
types of psychotherapy that have proven efficacy are mainly cognitive behavioral
therapy (CBT) and interpersonal psychotherapy (IPT). The efficacy of
psychoanalytic therapy has not been proven in methodologically sound studies,
despite its frequent use. Repetitive transcranial magnetic stimulation appears
promising for some subtypes of depression. Vagal nerve stimulation is most often
combined with antidepressant drugs for treatment-resistant depression. Light
therapy, also called phototherapy, is frequently combined with sleep deprivation.
It appears effective in some subtypes of depression. It is often prescribed
together with antidepressants.

PMID: 18356013 [PubMed – indexed for MEDLINE] J Affect Disord. 2008 Jul;109(1-2):21-34. Epub 2007 Nov 26.

Treatment of bipolar depression: an update.

Fountoulakis KN, Grunze H, Panagiotidis P, Kaprinis G.

3rd Department of Psychiatry, Aristotle University of Thessaloniki, Greece.

This article attempts to summarize the current status of our knowledge and
practice in the acute treatment and prophylaxis of bipolar depression. For
prophylactic treatment, our knowledge about lithium firmly supports its
usefulness against bipolar depression and its specific effectiveness for suicidal
prevention. Valproic acid and carbamazepine could be effective, too, while
lamotrigine which seems to be preferably effective against depression but not
mania. The FDA has approved the olanzapine-fluoxetine combination and quetiapine
monotherapy for the treatment of acute bipolar depression. The usefulness of
antidepressants in bipolar depression is controversial both for acute and
prophylactic treatment; guidelines suggest their cautious use and always in
combination with an antimanic and mood stabilizer agent, because in some patients
they may induce switching to mania or hypomania, mixed episodes and rapid
cycling. Data on psychosocial intervention are restricted to the maintenance
phase. Electroconvulsive therapy and transcranial magnetic stimulation are
additional options for refractory patients. Bipolar depression seems to be a more
difficult condition to treat than mania. Most patients need complex combination
treatment although the published evidence on this type of treatment is limited.

PMID: 18037498 [PubMed – indexed for MEDLINE] Int J Neuropsychopharmacol. 2008 Feb;11(1):131-47. Epub 2007 Sep 20.

A review of the safety of repetitive transcranial magnetic stimulation as a
clinical treatment for depression.

Loo CK, McFarquhar TF, Mitchell PB.

School of Psychiatry, University of New South Wales, Sydney, Australia.

There is growing interest worldwide in rTMS as a clinical treatment for
depression. Apart from efficacy, its safety as a clinical treatment must be
considered before its widespread use can be advocated. All published,
sham-controlled rTMS depression trials were reviewed for reported side-effects
and outcomes of formal neuropsychological testing. In addition, all reports of
seizures occurring with rTMS were reviewed. Other safety concerns (effects on
hearing; headache, pain, induced currents in electrical circuits, histotoxicity,
electromagnetic field exposure, psychiatric complications, safety in pregnancy)
are discussed. Common side-effects were of a minor nature, e.g. headache. There
was a low incidence of accidental seizures and induced hypomania, both of which
were associated with identified risk factors for which subjects should be
screened. Long-term effects of repeated rTMS sessions are as yet unknown. When
given within recommended guidelines, the overall safety profile of rTMS is good,
and supports its further development as a clinical treatment.

PMID: 17880752 [PubMed – indexed for MEDLINE] Encephale. 2007 Mar-Apr;33(2):126-34.

[Efficacy of repetitive transcranial magnetic stimulation (rTMS) in major
depression: a review].

[Article in French]

Brunelin J, Poulet E, Boeuve C, Zeroug-vial H, d’Amato T, Saoud M.

EA 3092, UCBL, Professeur J. Daléry, CH Le Vinatier, 95 boulevard Pinel, 69677
Bron cedex.

INTRODUCTION: In 1985, Barker et al. showed that it was possible to stimulate
both nerves and brain using external magnetic stimulation without significant
pain. During the past 10 years, therapeutic effects of repeated Transcranial
Magnetic Stimulation (rTMS) have been widely studied in psychiatry and its
efficacy has been demonstrated in the treatment of major depressive disorders,
particularly as an alternative to electroconvulsivotherapy (ECT). Facing the
large range of studies, we found necessary to propose an up-to-date review in
French of the methodological and therapeutic variations among them.
METHOD: Based on an exhaustive consultation of Medline data and the
Avery-George-Holtzheimer Database of rTMS Depression-Studies, supplemented by a
manual research, only works evaluating the therapeutic efficacy of rTMS on
depressive symptoms were retained, excluding all studies exclusively
investigating the stimulation parameters or the tolerance as well as case
RESULTS: Out the 66 available reports we retained 30 studies. After a description
of the main results of these 30 studies, several elements of the 66 will be
discussed. Open studies demonstrated that short courses rTMS (5 to 10 sessions)
produced a decrease in the mean Hamilton Depression Ratting Scale (HDRS) scores,
although significant remission of depression in individuals was rare. Most
authors had used high frequency rTMS applied to the left Dorso Lateral Prefrontal
Cortex (left DLPFC). However, low frequency rTMS applied to the right DLPFC was
also followed by significant reduction of HDRS scores. Parallel arm, double blind
versus placebo studies are designed to clarify the therapeutic efficacy of rTMS
therapy but conclude in contradicting results. Literature data globally confirms
a greater efficacy of rTMS compared to placebo (37% responders in the active
group vs 20% in the sham). This efficacy could in fact be even greater because
the sham procedure is disputable in most studies. Indeed, positioning rTMS coil
at 45 or 90 from the scalp may not represent an accurate sham procedure and the
use of real sham coil is to be recommended. Only one study has suggested that
associating rTMS and ECT could decrease the number of general anesthesia
required. Therapeutic efficacy has been shown by either inhibiting the right
DLPFC or by stimulating the left DLPFC, although some patients exhibit
paradoxical responses. High frequency rTMS (>5 Hz) increases cortical
excitability and metabolism, while low-frequency rTMS stimulation ( 1 Hz) has the
opposite effect. Other parameters are: relevant: intensity (from 80 to 110% of
motor threshold), total number of stimulations (from 120 to 2 000) and total
number of rTMS sessions (from 5 to 20). As suggested in most recent studies,
higher-intensity pulses, higher number of stimulation or longer treatment courses
may be more effective. Greater responsiveness to rTMS may be predicted by several
patients’ factors, including the absence of psychosis, younger age and previous
response to rTMS therapy.
DISCUSSION: Conclusions on these factors and others, such as the importance of
anatomically accurate coil placement and the distance from the coil to the brain,
await further investigation. Despite heterogeneity of these reports according to
methodology and treatment parameters, the antidepressive properties of rTMS now
appear obvious, opening interesting prospects, in particular in the treatment of
pharmacoresistant major depressive patients and, we hope, administered as
adjuvant therapy in non-resistant depression.
CONCLUSION: Thus, many questions remain unanswered concerning the optimal
stimulation parameters, privileged indications and maintenance sessions. This
justifies the development of structured evaluation trials on larger samples.

PMID: 17675907 [PubMed – indexed for MEDLINE] J Psychiatr Res. 2007 Apr-Jun;41(3-4):189-206. Epub 2006 Jul 25.

The burden of severe depression: a review of diagnostic challenges and treatment

Nemeroff CB.

Department of Psychiatry and Behavioral Sciences, Emory University School of
Medicine, 101 Woodruff Circle, Suite 4000, Atlanta, GA 30322, USA.

Among the factors making recognition of severe depression problematic for
clinicians are the heterogeneous nature of the condition, lack of standardized
definitions, and concomitant comorbidities that confound differential diagnosis
of symptoms. The spectrum of severity in depressive disorders is extraordinarily
broad, and severity assessment is comprised of several metrics including symptom
intensity, diagnostic subtypes, suicidality risk, and hospitalization status. The
overall diagnosis is achieved through consideration of symptom types and
severities together with the degree of functional impairment as assessed by the
psychiatric interview. It is likely that no single fundamental neurobiological
defect underlies severe depression. The chronicity and heterogeneity of this
disorder lead to frequent clinic visits and a longer course of treatment;
therefore, successful approaches may require an arsenal of treatments with
numerous mechanisms of action. The categories of drugs used to treat severe
depression are detailed herein, as are several non-pharmacologic options
including a number of experimental treatments. Pharmacotherapies include
tricyclic antidepressants, selective serotonin reuptake inhibitors, atypical
antidepressants such as serotonin-norepinephrine reuptake inhibitors and
monoamine oxidase inhibitors, and combination and augmentation therapies. Drugs
within each class are not equivalent, and efficacy may vary with symptom
severity. Patient adherence makes tolerability another critical consideration in
antidepressant choice. The role of non-pharmacological treatments such as
electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic
stimulation, and deep brain stimulation remain active avenues of investigation.
Improved knowledge and treatment approaches for severe depression are necessary
to facilitate remission, the ideal treatment goal.

PMID: 16870212 [PubMed – indexed for MEDLINE] Clin EEG Neurosci. 2007 Apr;38(2):105-15.

Transcranial and deep brain stimulation approaches as treatment for depression.

Rau A, Grossheinrich N, Palm U, Pogarell O, Padberg F.

Dept. of Psychiatry and Psychotherapy, Ludwig-Maximilians University Munich,
Munich, Germany.

Given that a considerable portion of depressed patients does not respond to or
remit during pharmacotherapy, there is increasing interest in non-pharmacological
strategies to treat depressive disorders. Several brain stimulation approaches
are currently being investigated as novel therapeutic interventions beside
electroconvulsive therapy (ECT), a prototypic method in this field with proven
effectiveness. These neurostimulation methods include repetitive transcranial
magnetic stimulation (rTMS), magnetic seizure therapy (MST), vagus nerve
stimulation (VNS), deep brain stimulation (DBS) and transcranial direct current
stimulation (tDCS). It is via different neuroanatomically defined “windows” that
the various approaches access the neuronal networks showing an altered function
in depression. Also, the methods vary regarding their degree of invasiveness. One
or the other method may finally achieve antidepressant effectiveness with
minimized side effects and constitute a new effective treatment for major

PMID: 17515176 [PubMed – indexed for MEDLINE] Neurophysiol Clin. 2006 May-Jun;36(3):157-83. Epub 2006 Aug 24.

Safety and efficacy of repetitive transcranial magnetic stimulation in the
treatment of depression: a critical appraisal of the last 10 years.

Rachid F, Bertschy G.

Département de psychiatrie, service de psychiatrie adulte, hôpitaux
universitaires de Genève, consultation de la jonction, 16-18, boulevard
Saint-Georges, 1205 Genève, Switzerland. rachidfady@yahoo.com

Depression is a common and debilitating illness, for which alternative treatments
are urgently needed. Repetitive transcranial magnetic stimulation (rTMS) is a
non-invasive and relatively painless experimental technique of altering brain
physiology. The authors critically review the evidence for the efficacy, safety
and tolerability of rTMS in the treatment of depression based on published data
over the last decade. They also discuss studies which have examined relevant
clinical, demographic, methodological, and technical parameters that might be
implicated in optimizing the antidepressant efficacy of this technique. rTMS
depression trials conducted through early 2006 are included in this review, which
focuses mainly on the results of published sham-controlled studies, literature
reviews and meta-analyses. Trials published so far have been characterized by the
use of a great variety of stimulation parameters, study designs, questionable
sham controls, small sample sizes and heterogeneously depressed populations, all
of which have made comparisons between studies difficult. Meta-analyses of 2-week
rTMS sham-controlled studies support, for the most part, the antidepressant
effects of rTMS which are statistically superior to sham. However, the degree of
clinical improvement remains small, although greater efficacy has been shown with
longer treatment courses and predictors of response to rTMS are progressively
being identified. rTMS is a promising antidepressant treatment with overall minor
adverse effects. Because the clinical efficacy of rTMS as an antidepressant
remains questionable, further systematic, large-scale multicenter studies
comparing rTMS to a sham and/or to an antidepressant medication along with more
stringent stimulation parameters are warranted in order to identify patient
populations most likely to benefit and treatment parameters most likely to
optimize its antidepressant efficacy.

PMID: 17046610 [PubMed – indexed for MEDLINE] Aust N Z J Psychiatry. 2006 May;40(5):406-13.

Transcranial magnetic stimulation for depression.

Mitchell PB, Loo CK.

School of Psychiatry, University of New South Wales, Black Dog Institute, Prince
of Wales Hospital, Randwick, Australia. phil.mitchell@unsw.edu.au

Comment in:
Aust N Z J Psychiatry. 2006 May;40(5):379-80.

OBJECTIVE: To review the accumulated literature on the efficacy, safety and
predictors of response for repetitive transcranial magnetic stimulation (rTMS) in
the treatment of depression.
METHODS: A descriptive review of the more than 25 published sham-controlled rTMS
studies in depression was undertaken, focusing on reported meta-analyses as well
as individual trial reports. Potential determinants of efficacy were examined,
including the form of shams employed, stimulation parameters and clinical
RESULTS: There is now clear evidence for the statistical superiority of
left-prefrontal high frequency rTMS compared with sham therapy. However, the
clinical benefits are marginal in the majority of reports. There is also still
considerable uncertainty concerning the optimal stimulation parameters. Those
clinical features which appear to be associated with greater response include
younger age, lack of refractoriness to antidepressants and no psychotic features.
CONCLUSIONS: Current studies confirm statistical efficacy, but insubstantive
clinical benefit. Large multicentre studies currently underway should clarify if
rTMS should be approved by regulatory agencies for widespread clinical
availability. Furthermore, there is a need to clarify the preferred parameters
for administering this treatment.

PMID: 16683966 [PubMed – indexed for MEDLINE] J Clin Psychiatry. 2006 Dec;67(12):1870-6.

Factors modifying the efficacy of transcranial magnetic stimulation in the
treatment of depression: a review.

Herrmann LL, Ebmeier KP.

Division of Psychiatry,University of Edinburgh, Edinburgh, United Kingdom.

OBJECTIVE: So far no convincing answer has emerged to the question of whether
transcranial magnetic stimulation (TMS) can make a clinically useful contribution
to the treatment of depression. Here we examine whether multiple sensitivity
analyses can highlight parameters that predict a favorable treatment response.
DATA SOURCES: Medline, Embase, and the Cochrane database for controlled trials
were searched for relevant randomized controlled trials using the expression
(transcranial magnetic stimulation or TMS) and depression.
STUDY SELECTION: Thirty-three studies were identified and included in the
random-effects meta-analysis, and between 17 and 31 studies were included in the
secondary analyses comparing outcome of studies with different parameters.
DATA EXTRACTION: Study data were extracted with a standardized data sheet. A
meta-analysis based on Cohen d effect size measure was done for all studies and
various subsets. Regression analysis of effect sizes with study parameters was
done in 24 studies.
DATA SYNTHESIS: Active TMS treatment was more effective than sham, but
variability was too great to take any single study design as paradigmatic. No
significant predictors of study effect size were found. Mean effect sizes were
reduced, although still significant, in studies with stimulation intensity below
90% of motor threshold and new medication starting within 7 days before to 7 days
after start of TMS.
CONCLUSIONS: The absence of significant outcome predictors in the presence of
significant variability of outcome measures can be interpreted in 2 ways: either
study sizes and numbers and designs are insufficient to afford the power
necessary to detect such predictors or TMS has a nonspecific effect on depression
that is not influenced by study parameters. Large-scale comparative trials are
necessary to decide between these interpretations.

PMID: 17194264 [PubMed – indexed for MEDLINE] Curr Pharm Des. 2006;12(4):503-15.

Recent progress in pharmacological and non-pharmacological treatment options of
major depression.

Baghai TC, Möller HJ, Rupprecht R.

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University of
Munich, Nussbaumstrasse 7, D-80336 Munich, Germany. Baghai@med.uni-muenchen.de

In spite of recent progress in the pharmacotherapy of depression major issues are
still unresolved. These include the non-response rate of approximately 30% to
conventional antidepressant pharmacotherapy, side effects of available
antidepressants and the latency of several weeks until clinical improvement. The
only non-pharmacological biological treatment options available so far which
exert more rapid antidepressant efficacy are electroconvulsive therapy and, as an
augmentation strategy, sleep deprivation. Current pharmacological treatments aim
to enhance serotonergic and/or noradrenergic neurotransmission. In spite of
emerging knowledge, the crucial mechanisms underlying both non-pharmacological
treatments, which are responsible for antidepressant efficacy, are not yet clear
so far. In the meantime several new pharmacological principles are under
investigation with regard to their putative antidepressant potency. These include
5-HT1A receptor agonists, tachykinin receptor antagonists and various
interventions within the hypothalamic-pituitary-adrenal system. While there is
evidence for antidepressant properties of these new treatments in animal studies,
in case series, in open studies and to some degree also in placebo controlled
studies, no definite proof for the antidepressant efficacy of these new
pharmacological strategies according to the requirements for evaluation of
antidepressant drugs has been furnished so far. In contrast, for the established
non-pharmacological treatment strategies including bright light therapy the
clinical efficacy has been proven at least in subgroups of depression, but more
knowledge of the main mechanisms underlying their antidepressant efficacy is
still necessary. In addition new non-pharmacological treatments like repetitive
transcranial magnetic stimulation, magnetic seizure therapy and Vagus nerve
stimulation are currently under development. Nevertheless, a follow-up of both
the new pharmacological strategies and non-pharmacological treatment options is
of major importance to provide even better strategies for the clinical management
of depression, which also is of great socio-economic impact.

PMID: 16472142 [PubMed – indexed for MEDLINE] Psychiatry Res. 2006 Nov 22;148(1):33-45. Epub 2006 Oct 5.

An analysis of functional neuroimaging studies of dorsolateral prefrontal
cortical activity in depression.

Fitzgerald PB, Oxley TJ, Laird AR, Kulkarni J, Egan GF, Daskalakis ZJ.

Alfred Psychiatry Research Centre, The Alfred and Monash University Department
of Psychological Medicine, Commercial Rd, Melbourne, Victoria 3004, Australia.

Repetitive transcranial magnetic stimulation (rTMS) is currently undergoing
active investigation for use in the treatment of major depression. Recent
research has indicated that current methods used to localize the site of
stimulation in dorsolateral prefrontal cortex (DLPFC) are significantly
inaccurate. However, little information is available on which to base a choice
of stimulation site. The aim of the current study was to systematically examine
imaging studies in depression to attempt to identify whether there is a pattern
of imaging results that suggests an optimal site of stimulation localization. We
analysed all imaging studies published prior to 2005 that examined patients with
major depression. Studies reporting activation in DLPFC were identified. The
DLPFC regions identified in these studies were analysed using the Talairach and
Rajkowska-Goldman-Rakic coordinate systems. In addition, we conducted a
quantitative meta-analysis of resting studies and studies of serotonin reuptake
inhibitor antidepressant treatment. There was considerable heterogeneity in the
results between studies. Changes in Brodmann area 9 were relatively consistently
identified in resting, cognitive activation and treatment studies included in
the meta-analysis. However, there was little consistency in the direction of
these changes or the hemisphere in which they were identified. At this stage,
the results of imaging studies published to date have limited capacity to inform
the choice of optimal prefrontal cortical region for the use in rTMS treatment

PMID: 17029760 [PubMed – in process] Int J Neuropsychopharmacol. 2006 Sep 7;:1-12 [Epub ahead of print]

A randomized trial of low-frequency right-prefrontal-cortex transcranial
magnetic stimulation as augmentation in treatment-resistant major depression.

Fitzgerald PB, Huntsman S, Gunewardene R, Kulkarni J, Daskalakis ZJ.

Alfred Psychiatry Research Centre, The Alfred and Monash University Department
of Psychological Medicine, Melbourne, Victoria, AustraliaThe Victoria Clinic,
Prahran, Melbourne, Australia.

Low-frequency right prefrontal repetitive transcranial magnetic stimulation
(rTMS) appears to have antidepressant properties although the effectiveness of
this treatment in clinical practice has not been assessed nor have the optimal
stimulation parameters been adequately defined. A total of 130 patients with
treatment-resistant depression were randomized to either 1- or 2-Hz rTMS over
the right prefrontal cortex (PFC) for 2 wk with a possible further 2 wk
extension. Non- responders were randomized to either 5- or 10-Hz left PFC rTMS.
Overall, 66 patients (51%) achieved response and 35 (27%) remission criteria.
For right-sided treatment, depression significantly improved but there was no
between-group difference. Twenty-eight (42%) patients in the 1-Hz group and 33
(53%) patients in the 2-Hz group achieved response criteria (chi2=1.40, p>0.05).
Depression symptom scores also improved for patients who crossed over to
left-sided treatment but there was no significant difference in response between
5- and 10-Hz rTMS. Despite a heterogeneous sample, a significant proportion of
patients met clinical response criteria following treatment but response to 1
and 2 Hz did not differ. 2-Hz right PFC rTMS has antidepressant properties but
offers no advantage over 1 Hz despite doubling pulse number.

PMID: 16959055 [PubMed – as supplied by publisher] Aust N Z J Psychiatry. 2006 Sep;40(9):764-8.

Naturalistic study of the use of transcranial magnetic stimulation in the
treatment of depressive relapse.

Fitzgerald PB, Benitez J, de Castella AR, Brown TL, Daskalakis ZJ, Kulkarni J.

Alfred Psychiatry Research Centre, Department of Psychological Medicine, Monash
University, Melbourne, Victoria, Australia. paul.fitzgerald@med.monash.edu.au

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS)
in the treatment of depression has been assessed in a number of acute treatment
trials during the last 10 years. Little is known about the long-term impact of
the treatment on the disorder and its effectiveness when applied for repeated
relapses of depression over time. METHOD: Nineteen patients who had previously
responded to rTMS in clinical trials received treatment with rTMS for a total of
30 episodes of depressive relapse. RESULTS: Approximately 10 months elapsed
between treatment episodes. The majority of patients achieved a significant
improvement in each treatment course with significant improvements achieved in
patients treated with both low-frequency right-sided rTMS and high-frequency
left-sided rTMS. CONCLUSIONS: The study suggests that rTMS may have value in the
treatment of episodes of depressive relapse with little reduction in efficacy
over time.

PMID: 16911751 [PubMed – in process] Aust N Z J Psychiatry. 2006 Sep;40(9):759-63.

Daily and spaced treatment with transcranial magnetic stimulation in major
depression: a pilot study.

Turnier-Shea Y, Bruno R, Pridmore S.

Department of Psychological Medicine, Royal Hobart Hospital, and School of
Psychology, University of Tasmania, Australia.

OBJECTIVE: Transcranial magnetic stimulation is an emerging treatment of
treatment-resistant depression. Current protocols rely on daily treatments. This
study was designed to determine whether the time period over which treatment is
delivered is an important factor in efficacy. METHOD: Sixteen adult patients
with treatment-resistant major depression were randomly assigned to one of the
two treatment groups, both of which received 2 weeks of treatment. One group
received daily treatment (10 treatments, on business days). The other group
received three treatments in week one, and two treatments in week two (five
treatments, on spaced business days). Mood was rated using the Hamilton
Depression Rating Scale (HDRS) and a self-rated visual analogue scale. Response
was defined as a 50% reduction in HDRS rating, and remission was defined as
achieving an HDRS score of 8 or less. The groups were compared throughout the
2-week study period. RESULTS: At entry, there were no demographic differences
between the groups. Multivariate tests showed a significant main effect for time
(Pillai trace=0.76, F(4,56)=8.56, p<0.001, power=0.99) reflecting the
improvement in both measures of depression during treatment. There was no
significant difference between the groups overall (Pillai trace=0.25,
F(2,13)=2.12, p=0.16, power=0.36). Additionally, there was no significant
interaction between time and treatment group (Pillai trace=0.18, F(4,56)=1.35,
p=0.26, power=0.39) indicating that the significant improvement in depression
over time was similar for both treatment groups. There were no significant
differences in response and remission rates between the groups. CONCLUSION: The
time period of treatment appeared to be an important outcome factor. This
suggests that less than daily transcranial magnetic stimulation treatment may be
a useful clinical alternative.

PMID: 16911750 [PubMed – in process] Int J Neuropsychopharmacol. 2006 Aug 21;:1-10 [Epub ahead of print]

Comparison of repetitive transcranial magnetic stimulation and electroconvulsive
therapy in unipolar non-psychotic refractory depression: a randomized,
single-blind study.

Rosa MA, Gattaz WF, Pascual-Leone A, Fregni F, Rosa MO, Rumi DO, Myczkowski M,
Silva MF, Mansur C, Rigonatti SP, Jacobsen Teixeira M, Marcolin MA.

Institute of Psychiatry, University of Sao Paulo, Sao Paulo – SP, Brazil.

Repetitive transcranial magnetic stimulation (rTMS) can induce significant
antidepressant effects and, for some patients, might be an alternative to
electroconvulsive therapy (ECT). The results of studies comparing the efficacy
of rTMS and ECT are mixed and, therefore, comparison of these two therapies
needs to be further explored. Forty-two patients aged between 18 and 65 yr,
referred to ECT due to unipolar non-psychotic depression refractoriness entered
the trial. They were randomly assigned to receive either rTMS or ECT. Depressive
symptom changes were blindly measured by Hamilton Depression Rating Scale,
Visual Analogue Scale and Clinical Global Impression at baseline, after 2 wk and
after 4 wk of treatment. There was no difference in the antidepressant efficacy
of ECT and rTMS. Response rates were relatively low in both groups (40% and 50%
respectively), with no significant difference between them (p=0.55). Remission
rates were also low for both groups (20% and 10% respectively), also with no
significant difference (p=0.631). There was no significant difference in the
neuropsychological test performance after either one of these therapies. Both
treatments were associated with a degree of improvement in refractory depression
and therefore add to the literature that rTMS can be an effective option to ECT
as it is a less costly treatment and is not associated with anaesthetic and
other ECT risks.

PMID: 16923322 [PubMed – as supplied by publisher] Prog Neuropsychopharmacol Biol Psychiatry. 2006 Jul;30(5):960-2. Epub 2006
Apr 24.

Repetitive transcranial magnetic stimulation (rTMS) in a patient suffering from
comorbid depression and panic disorder following a myocardial infarction.

Sakkas P, Psarros C, Papadimitriou GN, Theleritis CG, Soldatos CR.

Athens University Medical School, Psychiatry Department, Eginitio Hospital, 74
Vas. Sofias Avenue, Athens 11528, Greece. psakkas@cc.uoa.gr

Application of repetitive transcranial magnetic stimulation was effective and
safe in treating a 55-year-old man with comorbid depression and panic disorder,
which occurred 6 months after a myocardial infarction.

Publication Types:
Case Reports

PMID: 16631291 [PubMed – indexed for MEDLINE] Biol Psychol. 2006 Jun;72(3):271-7. Epub 2005 Dec 15.

Depressed mood, index finger force and motor cortex stimulation: a transcranial
magnetic stimulation (TMS) study.

Oathes DJ, Ray WJ.

Department of Psychology, The Pennsylvania State University, University Park, PA
16802, USA. djo155@psu.edu

The present study utilized transcranial magnetic stimulation (TMS) of the motor
cortex to understand basic motor processes associated with depressive symptoms
independent of cognitive requirements or diagnostic category. To assess the
integrity of the basic cortical-spinal-motor circuit associated with depressed
mood, TMS to the motor cortex was used to initiate motor evoked potentials
(MEPs) in forearm EMG and force production measured in the right (dominant)
index finger. While at rest, a group with more depressive symptoms showed less
force response in the index finger following stimulations compared with a group
endorsing less depressive symptoms. A negative correlation between force
response in the index finger at baseline (rest) following stimulation and the
Beck depression inventory indicated that depressive mood symptom elevations were
associated with less response to stimulations. The results argue for a greater
importance placed on the relationship between depressive mood symptoms and basic
motor processes.

PMID: 16359768 [PubMed – indexed for MEDLINE] Aust N Z J Psychiatry. 2006 May;40(5):406-13.

Comment in:
Aust N Z J Psychiatry. 2006 May;40(5):379-80.

Transcranial magnetic stimulation for depression.

Mitchell PB, Loo CK.

School of Psychiatry, University of New South Wales, Black Dog Institute, Prince
of Wales Hospital, Randwick, Australia. phil.mitchell@unsw.edu.au

OBJECTIVE: To review the accumulated literature on the efficacy, safety and
predictors of response for repetitive transcranial magnetic stimulation (rTMS)
in the treatment of depression. METHODS: A descriptive review of the more than
25 published sham-controlled rTMS studies in depression was undertaken, focusing
on reported meta-analyses as well as individual trial reports. Potential
determinants of efficacy were examined, including the form of shams employed,
stimulation parameters and clinical features. RESULTS: There is now clear
evidence for the statistical superiority of left-prefrontal high frequency rTMS
compared with sham therapy. However, the clinical benefits are marginal in the
majority of reports. There is also still considerable uncertainty concerning the
optimal stimulation parameters. Those clinical features which appear to be
associated with greater response include younger age, lack of refractoriness to
antidepressants and no psychotic features. CONCLUSIONS: Current studies confirm
statistical efficacy, but insubstantive clinical benefit. Large multicentre
studies currently underway should clarify if rTMS should be approved by
regulatory agencies for widespread clinical availability. Furthermore, there is
a need to clarify the preferred parameters for administering this treatment.

Publication Types:

PMID: 16683966 [PubMed – indexed for MEDLINE] J Psychopharmacol. 2006 May;20(3 Suppl):35-40.

Neurostimulation in resistant depression.

Carpenter LL.

Department of Psychiatry, Brown University, Providence, RI 02906, USA.

Drugs and psychotherapy are inadequate for relieving depressive symptoms in a
substantial portion of severely depressed patients. In that patient group,
neurostimulation techniques such as electroconvulsive therapy, transcranial
magnetic stimulation, magnetic seizure therapy, vagus nerve stimulation and deep
brain stimulation could be lifesaving therapies. Neurostimulation is a physical
intervention that utilizes application of either electric current or a magnetic
field to directly stimulate the brain or central nervous system. This article
presents an overview of currently available neurostimulatory techniques for
depression, including a review of their efficacy and safety. Further development
and evaluation of non-pharmacological antidepressant therapies are needed, with
the hope of improving treatment of refactory depression.

PMID: 16644770 [PubMed – in process] J Psychiatr Res. 2006 Mar 20; [Epub ahead of print]

Positive predictors for antidepressive response to prefrontal repetitive
transcranial magnetic stimulation (rTMS).

Brakemeier EL, Luborzewski A, Danker-Hopfe H, Kathmann N, Bajbouj M.

Department of Psychiatry and Psychotherapy, Charite – Universitatsmedizin
Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany.

Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation
technique which had recently been investigated as a putative antidepressant
intervention. However, there is little agreement about clinically useful
predictors of rTMS outcome. Therefore, the objective of the present study was to
determine whether specific biographical, clinical, and psychopathological
parameters are associated with the antidepressant response to rTMS in a large
sample of 70 depressive patients. We performed a logistic regression analysis in
70 patients with major depressive disorder treated with rTMS of the left
dorsolateral prefrontal cortex testing the predictive value of various domains
of the depression syndrome as well as the variables episode duration, degree of
treatment resistance, and CORE criteria. Response was defined as a 50% reduction
of the initial Hamilton score (HAMD). After two weeks of treatment, 21% of the
patients showed a response to rTMS. The binary logistic regression model
correctly assigned 86.7% of the responders and 96.4% of the non-responders to
their final response group. In the model, a high level of sleep disturbances was
a significant predictor for treatment response to rTMS. Also, a low score of
treatment resistance and a short duration of episode were positive predictors.
These findings provide new evidence that especially pronounced sleep
disturbances may be a significant clinical predictor of a response to rTMS.
Prospective rTMS studies are necessary to validate the predictive value of the
derived model.

PMID: 16554071 [PubMed – as supplied by publisher] Australas Psychiatry. 2006 Mar;14(1):81-5.

Transcranial magnetic stimulation in adolescent depression.

Loo C, McFarquhar T, Walter G.

School of Psychiatry, University of New South Wales, Australia.

OBJECTIVE: There are few safe and effective biological treatments for major
depression in adolescents. We aimed to report the use of repetitive transcranial
magnetic stimulation (rTMS) as a treatment for adolescents with this condition.
METHODS: The first two subjects in a double-blind, sham-controlled trial of rTMS
that is evaluating the efficacy and safety of rTMS in depressed adolescents are
described. Clinical response was assessed at baseline and at the end of each
week. The following scales were used: Montgomery-Asberg Depression Rating Scale,
Clinical Global Impression-Severity Scale, Beck Depression Inventory and Centre
for Epidemiological Studies – Depression – Child Scale. A battery of cognitive
tests was also used at several intervals to measure potential change in
neuropsychological functioning. RESULTS: Random allocation of both subjects was
to active treatment. Both subjects improved to a clinically significant degree
with rTMS treatment and reported no adverse effects. Neuropsychological testing
did not demonstrate any deterioration in the domains of functioning tested.
CONCLUSIONS: Repetitive transcranial magnetic stimulation shows early promise as
a treatment for major depression in adolescents. Well-designed, sham-controlled
studies are now indicated to test the efficacy and safety of rTMS in these

Publication Types:
Case Reports
Randomized Controlled Trial

PMID: 16630205 [PubMed – indexed for MEDLINE] Pharmacopsychiatry. 2006 Mar;39(2):52-9.

High-frequency repetitive transcranial magnetic stimulation improves refractory
depression by influencing catecholamine and brain-derived neurotrophic factors.

Yukimasa T, Yoshimura R, Tamagawa A, Uozumi T, Shinkai K, Ueda N, Tsuji S,
Nakamura J.

Department of Psychiatry, University of Occupational and Environmental Health,
1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a
non-invasive and easily tolerated method of altering cortical physiology. To
date, numerous open and sham controlled clinical trials have explored the
antidepressant potential of rTMS. In the present study, we investigated clinical
trials of high-frequency rTMS (20 Hz) for treatment of refractory depression,
and also examined the effect of rTMS on plasma levels of catecholamine
metabolites and brain-derived neurotropic factor (BDNF). METHODS: Twenty-six
depressed inpatients who met the DSM-IV criteria for major depressive disorder
and had failed to respond to treatment with at least two antidepressant drugs
given at adequate doses (above 150 mg/day in an equivalent dose of imipramine)
and durations (at least 4 weeks for each drug) were enrolled in this study.
Eleven were males, 15 females. The ages of the subjects ranged from 19 to 78
years old (mean +/- SD = 52.9 +/- 17.8). All patients were administered left
prefrontal 20 Hz rTMS at 80 % MT (total 800 pulses a day) over ten daily
sessions. The plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and
homovanillic acid (HVA) were analyzed by high-performance liquid chromatography.
The plasma levels of BDNF were also measured with the sandwich ELISA method.
RESULTS: The mean 17-item Hamilton Rating Scale for Depression (Ham-D) score of
20.5 +/- 5.2 before rTMS was significantly decreased to 15.6 +/- 7.3 after rTMS.
Nine of 26 patients (35 %) demonstrated some improvement (Ham-D > or = 25 %) by
rTMS. The levels of plasma MHPG, but not those of HVA, were significantly
reduced after rTMS treatment, and a negative correlation was observed between
the change in plasma MHPG levels and the change in scores of agitation. In
addition, the plasma levels of BDNF were significantly increased by 23 % in
responders and partial responders, but not in nonresponders, after rTMS
treatment, and a trend for association was found between the changes in Ham-D
scores and changes in plasma BDNF levels in all patients after rTMS treatment.
CONCLUSION: These results suggest that rTMS treatment brings about some
improvement in refractory depression, especially for symptoms such as agitation,
by influencing MHPG and BDNF, which is in accordance with previous reports
showing that BDNF was increased by various antidepressants treatments.

PMID: 16555165 [PubMed – indexed for MEDLINE] Psychiatry Res. 2006 Jan 30;141(1):1-13. Epub 2005 Dec 13.

Effect of low-frequency transcranial magnetic stimulation on an affective
go/no-go task in patients with major depression: role of stimulation site and
depression severity.

Bermpohl F, Fregni F, Boggio PS, Thut G, Northoff G, Otachi PT, Rigonatti SP,
Marcolin MA, Pascual-Leone A.

Harvard Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, MA 02215, USA. felix.bermpohl@charite.de

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a
therapeutic tool in major depression. However, a means to assess the effects of
a single rTMS session on mood to guide subsequent sessions would be desirable.
The present study examined the effects of a single rTMS session on an affective
go/no-go task known to measure emotional-cognitive deficits associated with
major depression. Ten patients with an acute episode of unipolar major
depression and eight partially or completely remitted (improved) patients
underwent 1 Hz rTMS over the left and right dorsolateral prefrontal cortex prior
to task performance. TMS over the mesial occipital cortex was used as a control.
We observed significantly improved performance in depressed patients following
right prefrontal rTMS. This beneficial effect declined with decreasing
depression severity and tended to reverse in the improved group. Left prefrontal
rTMS had no significant effect in the depressed group, but it resulted in
impaired task performance in the improved group. Our findings indicate that the
acute response of depressed patients to rTMS varies with the stimulation site
and depression severity. Further studies are needed to determine whether the
present paradigm could be used to predict antidepressant treatment success or to
individualize stimulation parameters according to specific pathology.

PMID: 16352348 [PubMed – indexed for MEDLINE] Biol Psychiatry. 2006 Jan 15;59(2):187-94. Epub 2005 Sep 1.

A controlled study of repetitive transcranial magnetic stimulation in
medication-resistant major depression.

Avery DH, Holtzheimer PE 3rd, Fawaz W, Russo J, Neumaier J, Dunner DL, Haynor
DR, Claypoole KH, Wajdik C, Roy-Byrne P.

Department of Psychiatry and Behavioral Sciences, University of Washington
School of Medicine, Harborview Medical Center, Seattle, 98104-2499, USA.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) as a treatment
for depression has shown statistically significant effects, but the clinical
significance of these effects has been questioned. METHODS: Patients with
medication-resistant depression were randomized to receive 15 sessions of active
or sham repetitive TMS delivered to the left dorsolateral prefrontal cortex at
110% the estimated prefrontal cortex threshold. Each session consisted of 32
trains of 10 Hz repetitive TMS delivered in 5-second trains. The primary end
point was treatment response defined as a >or=50% decrease in Hamilton
Depression Rating Scale (HDRS) score at both 1 and 2 weeks following the final
repetitive TMS treatment. Remission was defined as a HDRS score < 8. RESULTS:
The response rate for the TMS group was 30.6% (11/35), significantly (p = .008)
greater than the 6.1% (2/33) rate in the sham group. The remission rate for the
TMS group was 20% (7/35), significantly (p = .033) greater than the 3% (1/33)
rate in the sham group. The HDRS scores showed a significantly (p < .002)
greater decrease over time in the TMS group compared with the sham group.
CONCLUSIONS: Transcranial magnetic stimulation can produce statistically and
clinically significant antidepressant effects in patients with
medication-resistant major depression.

Publication Types:
Randomized Controlled Trial

PMID: 16139808 [PubMed – indexed for MEDLINE] Am J Psychiatry. 2006 Jan;163(1):88-94.

A randomized, controlled trial of sequential bilateral repetitive transcranial
magnetic stimulation for treatment-resistant depression.

Fitzgerald PB, Benitez J, de Castella A, Daskalakis ZJ, Brown TL, Kulkarni J.

Alfred Psychiatry Research Centre, the Alfred and Monash University Department
of Psychological Medicine, Melbourne, Victoria, Australia.

OBJECTIVE: High-frequency left-side repetitive transcranial magnetic stimulation
(rTMS) and low-frequency stimulation to the right prefrontal cortex have both
been shown to have antidepressant effects, but doubts remain about the magnitude
of previously demonstrated treatment effects. The authors evaluated sequentially
combined high-frequency left-side rTMS and low-frequency rTMS to the right
prefrontal cortex for treatment-resistant depression. METHOD: The authors
conducted a 6-week double-blind, randomized, sham-controlled trial in 50
patients with treatment-resistant depression. Three trains of low-frequency rTMS
to the right prefrontal cortex of 140 seconds’ duration at 1 Hz were applied
daily, followed immediately by 15 trains of 5 seconds’ duration of
high-frequency left-side rTMS at 10 Hz. Sham stimulation was applied with the
coil angled at 45 degrees from the scalp, resting on the side of one wing of the
coil. The primary outcome variable was the score on the Montgomery-Asberg
Depression Rating Scale. RESULTS: There was a significantly greater response to
active than sham stimulation at 2 weeks and across the full duration of the
study. A significant proportion of the study group receiving active treatment
met response (11 of 25 [44%]) or remission (nine of 25 [36%]) criteria by study
end compared to the sham stimulation group (two of 25 [8%] and none of 25
respectively). CONCLUSIONS: Sequentially applying both high-frequency left-side
rTMS and low-frequency rTMS to the right prefrontal cortex, has substantial
treatment efficacy in patients with treatment-resistant major depression. The
treatment response accumulates to a clinically meaningful level over 4 to 6
weeks of active treatment.

Publication Types:
Randomized Controlled Trial

PMID: 16390894 [PubMed – indexed for MEDLINE] Expert Rev Neurother. 2006 Jan;6(1):73-80.

Current and emerging somatic treatment strategies in psychotic major depression.

Dannon PN, Lowengrub K, Gonopolski Y, Kotler M.

The Rehovot Community Mental & Rehabilitation Center, Tel Aviv University,
Rehovot, Israel. pinhasd@post.tau.ac.il

Psychotic major depressive disorder (MDD) is a mood disorder characterized by
severe affective and neurovegetative symptoms together with the presence of
delusions and/or hallucinations. It is a common disorder seen in a quarter of
consecutively admitted depressed patients and is often associated with severe
symptomatology, increased suicide risk, poor acute response to antidepressants
and poor acute and long-term treatment outcome. It is possible that poor
response in psychotic depression is caused by the fact that we have yet to
identify the most efficacious treatment protocol for psychotic MDD. Multiple
studies have shown that modifications in the treatment paradigm may increase
treatment efficacy in psychotic MDD. It has been generally accepted that, during
the acute treatment phase, antidepressant-antipsychotic drug combination therapy
is more effective than either treatment alone, although this strategy has
recently been challenged. The question of the optimal duration of
pharmacotherapy in order to prevent relapse and improve long-term (i.e., 5-year)
outcome is a focus of current investigation. This article will review currently
recommended treatment strategies for the acute, continuation and maintenance
phases of therapy. In particular, it will address the role of newer-generation
antidepressants, the role of second-generation antipsychotics, the use of mood
stabilizers and indications for electroconvulsive therapy. Other possible
treatment strategies such as transcranial magnetic stimulation, vagus nerve
stimulation, deep-brain stimulation and glucocorticoid receptor antagonists will
be discussed. Current recommendations for the prevention of relapse and
improvement of long-term outcome will be reviewed.

Publication Types:

PMID: 16466314 [PubMed – indexed for MEDLINE] Prog Neuropsychopharmacol Biol Psychiatry. 2006 Jan;30(1):126-30. Epub 2005
Oct 20.

A double-blind sham controlled study of right prefrontal repetitive transcranial
magnetic stimulation (rTMS): therapeutic and cognitive effect in medication free
unipolar depression during 4 weeks.

Januel D, Dumortier G, Verdon CM, Stamatiadis L, Saba G, Cabaret W, Benadhira R,
Rocamora JF, Braha S, Kalalou K, Vicaut PE, Fermanian J.

Unite de recherche clinique, EPS de Ville Evrard a Saint Denis, G03, 5 Rue du Dr
Delafontaine 93200 Saint-Denis, France. urcve@freesurf.fr

BACKGROUND: Transcranial magnetic stimulation (TMS) has become a therapeutic
tool in psychiatric diseases. METHODOLOGY: The objective was to evaluate the
efficacy of TMS in unipolar depression: the percentage of responders (>50% HDRS
reduction) and remission (HDRS score < or =8, after four weeks of active TMS
treatment in depressed patients free of any antidepressive agent versus
placebo-TMS. RESULTS: 27 patients were randomized in two groups: rTMS (N=11)
versus sham TMS (N=16). Statistical differences were detected between sham and
TMS treated groups on remission (0/16 versus 4/11 p=0.032, 1/16 versus 6/11
0.028 and 1/16 versus 7/11 p=0.011 at day 14, day 21 and day 28, respectively)
and on response (2/16 versus 5/11 at day 14 (NS), 2/16 versus 7/11 p=0.0115 at
day 21 and 1/16 versus 7/11 (p=0.025) day 28, respectively, using the exact
Fisher test). Significant differences were observed between day 1 versus day 8
(p<0.01), day 15, day 21 and day 28 (p<0.001) in TMS group and only versus day
21 (p<0.01) and day 28 (p<0.05) for the sham group. ANOVA comparison between TMS
and sham groups was significant at day 14 and day 28 (p<0.05). LIMITATIONS: The
few number of patients. CONCLUSION: Our study has shown an efficacy of right
rTMS in free medication unipolar depression over a month. Nevertheless, number
of patients included is limited and multicentric studies will be necessary to
specify the antidepressive action of TMS.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 16242826 [PubMed – indexed for MEDLINE] World J Biol Psychiatry. 2006;7(4):261-4.

Induction of a mixed depressive episode during rTMS treatment in a patient with
refractory major depression.

Rachid F, Golaz J, Bondolfi G, Bertschy G.

Division of Adult Psychiatry, University Hospitals of Geneva, Switzerland.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive
experimental technique which has mostly been investigated in the treatment of
mood disorders with possible efficacy in depression. Among its potential side
effects, there have been some reports of rTMS-induced (hypo)mania in the
literature but none for rTMS-induced mixed episodes. We report the case of a
39-year-old woman suffering from refractory chronic major depression who
developed a depressive mixed episode associated with a mild serotonin syndrome
during her second week of rTMS treatment. She was receiving a combination of
antidepressants, the doses of which were kept unchanged during rTMS treatment.
Mixed as well as manic episodes may be induced by transcranial magnetic
stimulation, complications already observed with antidepressants and
electroconvulsive therapy. Therefore, caution should be exercised among
clinicians using this experimental procedure, particularly in the treatment of
bipolar depressed patients.

PMID: 17071547 [PubMed – in process] Nurs Stand. 2005 May 25-31;19(37):49-50.

Transcranial magnetic stimulation for patients with depression.

Tredget J, Kirov G, Dunn E.

Mood Disorders Service, Wales College of Medicine, Cardiff. tredgetj@cf.ac.uk

Transcranial magnetic stimulation (TMS) is a relatively new technique which has
been used to treat depression. It delivers magnetic radiation to the head using a
hand-held coil. Some studies have indicated clinical remission of depressive
symptomatology with use of TMS. Methodological limitations remain, however, and
more studies are recommended to determine its efficacy.

PMID: 15938414 [PubMed – indexed for MEDLINE] Cogn Behav Neurol. 2005 Dec;18(4):223-7.

The effects of repetitive transcranial magnetic stimulation (rTMS) on procedural
memory and dysphoric mood in patients with major depressive disorder.

O’Connor MG, Jerskey BA, Robertson EM, Brenninkmeyer C, Ozdemir E, Leone AP.

Harvard Medical School, Boston, MA, USA. moconnor@caregroup.harvard.edu

OBJECTIVE: To study the effects of depression and treatment with repetitive
transcranial magnetic stimulation (rTMS) on sequence learning. BACKGROUND:
Prefrontal dysfunction in depression may affect sequence learning and be
amenable to normalization by rTMS. METHOD: The serial reaction time test (SRTT)
was administered to 19 patients with major depressive disorder (MDD) and 20
nondepressed control participants. MDD patients were examined before and
following treatment with rTMS to the left dorsolateral prefrontal cortex in
daily sessions of 1600 stimuli at 10 Hz and at an intensity of 110% of the motor
threshold. Treatment occurred over a 2-week interval of time. RESULTS: MDD and
nondepressed groups differed significantly with respect to baseline response
speed. Following treatment with rTMS, MDD participants demonstrated
significantly improved mood, improved response speed, and improved procedural
learning. CONCLUSIONS: Findings suggest that rTMS over a 2-week period improves
performance on tasks of response speed and procedural memory in patients with
MDD. These cognitive effects are greater in those patients who showed a
significant antidepressant effect to rTMS intervention.

Publication Types:
Clinical Trial

PMID: 16340396 [PubMed – indexed for MEDLINE] J Clin Psychiatry. 2005 Dec;66(12):1569-75.

Does rTMS hasten the response to escitalopram, sertraline, or venlafaxine in
patients with major depressive disorder? A double-blind, randomized,
sham-controlled trial.

Rossini D, Magri L, Lucca A, Giordani S, Smeraldi E, Zanardi R.

Department of Psychiatry, School of Medicine, Vita-Salute University, San
Raffaele Hospital, Via Stamina d’Ancona 20, 20127 Milan, Italy.

BACKGROUND/OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has
been mainly studied as adjunctive treatment for drug-resistant patients. We
assessed the effectiveness of rTMS started concomitantly with antidepressant
medications in non-drug-resistant major depressive disorder patients. We also
evaluated if, among the 3 antidepressants administered, one had a better synergy
with rTMS. METHOD: In this 5-week, double-blind, randomized, sham-controlled
study, we recruited 99 inpatients suffering from a major depressive episode
(DSM-IV criteria). They were randomly assigned to receive venlafaxine,
sertraline, or escitalopram in combination with a 2-week period of sham or
active 15-Hz rTMS on the left dorso-lateral prefrontal cortex. Data were
gathered from February 2004 to June 2005. RESULTS: The active rTMS group showed
a significantly faster reduction in Hamilton Rating Scale for Depression (HAM-D)
scores compared with the sham group (p = .0029). The response and remission
rates were significantly greater in the active rTMS group after the stimulation
period (p = .002 and p = .003, respectively), but not at the endpoint. We found
no significant difference in HAM-D score reduction among the 3 drugs
administered, either in the active or in the sham group. CONCLUSION: These
findings support the efficacy of rTMS in hastening the response to
antidepressant drugs in patients with major depressive disorder. The effect of
rTMS seems to be unaffected by the specific concomitantly administered drug.

Publication Types:
Randomized Controlled Trial

PMID: 16401159 [PubMed – indexed for MEDLINE] J Clin Psychiatry. 2005 Dec;66(12):1524-8.

Long-term maintenance therapy for major depressive disorder with rTMS.

O’Reardon JP, Blumner KH, Peshek AD, Pradilla RR, Pimiento PC.

Department of Psychiatry, University of Pennsylvania, Ste. 4005, 3535 Market
Street, Philadelphia, PA 19104, USA. oreardon@mail.med.upenn.edu

OBJECTIVE: There is growing evidence to support the short-term antidepressant
effects of repetitive transcranial magnetic stimulation (rTMS), but few
published data pertain to the maintenance treatment of patients with
DSM-IV-diagnosed major depressive disorder who have responded acutely to rTMS.
We describe long-term maintenance therapy for major depressive disorder with
rTMS. METHOD: Repetitive transcranial magnetic stimulation was applied in 10
adults over the left prefrontal cortex at 100% of motor threshold, most often at
a frequency of 10 Hz for sessions consisting of 40 trains at 5 seconds per train
(2000 pulses per session), for periods ranging from 6 months to 6 years. Session
frequency averaged 1 to 2 per week. The study was conducted in the TMS lab of an
academic medical center. RESULTS: Seven of the 10 subjects experienced either
marked or moderate benefit, which was sustained without the addition of
concomitant antidepressant medication in 3 cases. There were no serious adverse
events reported by any participant. The seizure rate for the 1831 reported rTMS
sessions was zero. CONCLUSIONS: These data, while open label, suggest that
maintenance rTMS may be a safe and effective treatment modality in some patients
with unipolar depression. Further research into the long-term safety and
efficacy of rTMS is warranted.

Publication Types:
Case Reports
Clinical Trial
Randomized Controlled Trial

PMID: 16401152 [PubMed – indexed for MEDLINE] Int J Neuropsychopharmacol. 2005 Nov 23;:1-14 [Epub ahead of print]

Predictors of antidepressant response in clinical trials of transcranial
magnetic stimulation.

Fregni F, Marcolin MA, Myczkowski M, Amiaz R, Hasey G, Rumi DO, Rosa M,
Rigonatti SP, Camprodon J, Walpoth M, Heaslip J, Grunhaus L, Hausmann A,
Pascual-Leone A.

Harvard Center for Noninvasive Brain Stimulation, Beth Israel Medical Center,
Harvard Medical School, Boston, MA, USA.

Although previous clinical trials have suggested that repetitive transcranial
magnetic stimulation (rTMS) has a significant antidepressant effect, the results
of these trials are heterogeneous. We hypothesized that individual patients’
characteristics might contribute to such heterogeneity. Our aim was to identify
predictors of antidepressant response to rTMS. We pooled data from six separate
clinical trials conducted independently, which evaluated the effects of rapid
rTMS of the left dorsolateral prefrontal cortex in patients with major
depression. We investigated 195 patients with regard to demographic, depression
and treatment characteristics, psychiatric and drug history. Results showed that
age and treatment refractoriness were significant negative predictors of
depression improvement when adjusting these variables to other significant
predictors and confounders. These findings were not confounded by methodological
differences from the six studies, as the results were adjusted for the study
site. In conclusion TMS antidepressant therapy in younger and less
treatment-resistant patients is associated with better outcome.

PMID: 16939662 [PubMed – as supplied by publisher] Psychiatry Res. 2005 Nov 15;137(1-2):1-10. Epub 2005 Oct 12.

Transcranial magnetic stimulation in treatment-resistant depressed patients: a
double-blind, placebo-controlled trial.

Rossini D, Lucca A, Zanardi R, Magri L, Smeraldi E.

Department of Psychiatry, School of Medicine, Vita-Salute University, San
Raffaele Hospital, via Stamira d’Ancona 20, Milan 20127, Italy.

This 5-week, randomized, double-blind, placebo-controlled trial investigated the
efficacy and tolerability of high frequency repetitive transcranial magnetic
stimulation (rTMS) directed to the left prefrontal cortex in drug-resistant
depressed patients. Fifty-four patients were randomly assigned to receive 10
daily applications of either real or sham rTMS. Subjects assigned to receive
active stimulation were divided into two further subgroups according to the
intensity of stimulation: 80% vs. 100% of motor threshold (MT). At study
completion, the response rates were 61.1% (n=11), 27.8% (n=5) and 6.2% (n=1) for
the 100% MT group, 80% MT group and sham group, respectively. A significant
difference (Pearson chi(2) test) was found between the 100% MT and sham groups,
while the 80% MT group did not differ significantly from the sham group. Between
the two active groups, a marginally significant difference was observed.
Analysis of variance with repeated measures on Hamilton Depression Rating Scale
scores revealed a significantly different decrease over time of depressive
symptomatology among the three treatment groups. Treatment response appeared to
be unrelated to the demographic and clinical characteristics recorded, and on
the whole the technique was well tolerated. The results of this double-blind
trial showed that rTMS may be a useful and safe adjunctive treatment for
drug-resistant depressed patients.

Publication Types:
Randomized Controlled Trial

PMID: 16225930 [PubMed – indexed for MEDLINE] Neuroreport. 2005 Nov 7;16(16):1839-42.

Effects of repetitive transcranial magnetic stimulation in depression: a
magnetoencephalographic study.

Maihofner C, Ropohl A, Reulbach U, Hiller M, Elstner S, Kornhuber J, Sperling W.

Department of Neurology, University of Erlangen, Nuremberg, Erlangen, Germany.

Recently, repetitive transcranial magnetic stimulation has evolved as a
potential therapeutic tool to interfere with brain changes associated with
neurological and psychiatric diseases. Little is known about its mode of action,
however. Here, we investigated effects of repetitive transcranial magnetic
stimulation on spontaneous magnetoencephalographic activity in patients with
major depression. Before treatment, depressed patients showed a significant
increase in slow magnetoencephalographic activity (2-6 Hz) over the left
prefrontal cortex, compared with healthy controls. This activity significantly
decreased during 10 days of repetitive transcranial magnetic stimulation,
paralleled by clinical improvement. We conclude that therapeutic repetitive
transcranial magnetic stimulation effects can be mirrored by changes of
spontaneous magnetoencephalographic activity.

Publication Types:
Clinical Trial

PMID: 16237338 [PubMed – indexed for MEDLINE] J Affect Disord. 2005 Nov;88(3):255-67. Epub 2005 Sep 2.

A review of the efficacy of transcranial magnetic stimulation (TMS) treatment
for depression, and current and future strategies to optimize efficacy.

Loo CK, Mitchell PB.

School of Psychiatry, University of NSW, Psychiatrist, Black Dog Institute and
South Eastern Sydney Illawarra Area Health Service, Australia.

BACKGROUND: There is a growing interest in extending the use of repetitive
transcranial magnetic stimulation (rTMS) beyond research centres to the
widespread clinical treatment of depression. Thus it is timely to critically
review the evidence for the efficacy of rTMS as an antidepressant treatment.
Factors relevant to the efficacy of rTMS are discussed along with the
implications of these for the further optimization of rTMS. METHOD: Clinical
trials of the efficacy of rTMS in depressed subjects are summarized and
reviewed, focusing mainly on sham-controlled studies and meta-analyses published
to date. RESULTS: There is a fairly consistent statistical evidence for the
superiority of rTMS over a sham control, though the degree of clinical
improvement is not large. However, this data is derived mainly from two-week
comparisons of rTMS versus sham, and evidence suggests greater efficacy with
longer treatment courses. Studies so far have also varied greatly in approaches
to rTMS stimulation (with respect to stimulation site, stimulus parameters etc)
with little empirical evidence to inform on the relative merits of these
approaches. LIMITATIONS: Only studies published in English were reviewed. Many
of the studies in the literature had small sample sizes and different
methodologies, making comparisons between studies difficult. CONCLUSIONS:
Current published studies and meta-analyses have evaluated the efficacy of rTMS
as given in treatment paradigms that are almost certainly suboptimal (e.g of two
weeks’ duration). While the data nevertheless supports positive outcomes for
rTMS, there is much scope for the further refinement and development of rTMS as
an antidepressant treatment. Ongoing research is critical for optimizing the
efficacy of rTMS.

Publication Types:

PMID: 16139895 [PubMed – indexed for MEDLINE] Psychiatry Clin Neurosci. 2005 Aug;59(4):425-32.

Clinical application of single-pulse transcranial magnetic stimulation for the
treatment of depression.

Fujita K, Koga Y.

Kyorin University School of Medicine Department of Neuropsychiatry, Mitaka,
Tokyo, Japan.

Abstract Transcranial magnetic stimulation (TMS) has been recently suggested for
the treatment of patients with major depression. Based on the results of the
authors’ pilot study showing a possible antidepressive effect of single-pulse
TMS, a clinical trial was conducted involving patients with major depression.
For the present study single-photon emission computed tomography (SPECT) was
recorded for six of the target patients to study the effects of TMS on the local
blood flow volume. Twenty-three inpatients meeting the Diagnostic and
Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria for major
depression were invited to participate in the study. Depressive symptoms were
rated using the Hamilton Rating Scale for Depression (HAM-D). Patients were
given 10 stimuli over the frontal area of both sides for a total of 20 stimuli
in a session. The subjects had daily TMS session for 5 days as an add-on
therapy. In addition, six patients had their quantitative (99m)Tc-ethyl
cysteinate dimer SPECT images measured before and after TMS treatment. Compared
with the value 2 days prior to the start of TMS therapy (24.2 +/- 4.9), the
average HAM-D scale dropped significantly to 15.3 +/- 6.6 on the day after
completion of such therapy. The results of SPECT showed that the regional
cerebral blood flow (rCBF) of the bilateral frontal region had increased in four
out of six patients when comparing before and after treatment. The present study
shows that single-pulse TMS, which is widely used as a neurological test method,
possesses a wide range of antidepressive effects without inducing adverse
reactions. The results suggest that although repetitive TMS is steadily becoming
the mainstay technique today, single-pulse TMS also possesses sufficient
antidepressive effects.

PMID: 16048448 [PubMed – in process] J Clin Psychiatry. 2005 Jul;66(7):930-937.

Add-On rTMS for Medication-Resistant Depression: A Randomized, Double-Blind,
Sham-Controlled Trial in Chinese Patients.

Su TP, Huang CC, Wei IH.

From the Department of Psychiatry, Taipei Veterans General Hospital (Dr. Su and
Dr. Huang); the Division of Psychiatry, School of Medicine (Dr. Su), and the
Institute of Clinical Medicine (Dr. Huang), National Yang-Ming University; and
the Department of Anatomy and Cell Biology, College of Medicine, National Taiwan
University (Dr. Wei), Taipei, Taiwan.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been
developed as a novel tool for improving depression by delivering magnetic
stimulation to the brain. However, the apparent effects of rTMS on depression
have been varied in different studies. The aims of this study were to determine
whether left dorsolateral prefrontal cortex rTMS can alleviate
medication-resistant depression in Chinese patients and to investigate what
demographic variables or clinical features may predict better response. METHOD:
We designed a 2-week randomized, double-blind, sham-controlled study of add-on
rTMS. A total of 30 medication-resistant patients with DSM-IV major depressive
disorder or bipolar disorder, depressed episode completed 10 sessions of active
or sham rTMS-10 patients at each of 2 frequencies, faster (20 Hz) or slower (5
Hz) at 100% motor threshold, and 10 patients at sham stimulation. RESULTS:
Patients at both stimulation frequencies demonstrated a superior reduction of
depression severity compared to sham stimulation (active = 55.7% vs. sham =
16.3%). The response rate for active rTMS was 60%, in contrast to 10% for the
sham treatment. No difference in clinical response was observed between 5 Hz and
20 Hz active rTMS. Clinical variables showed that younger age and less severe
depression at entry may predict the clinical response to rTMS. Except for 1
patient in which rTMS appeared to induce mania, this procedure posed no safety
problem. CONCLUSIONS: To our knowledge, this is the first study to demonstrate
the clinical efficacy and safety of rTMS in Chinese patients. Since not all the
rTMS trials in previous reports had positive results, further larger trials are
still warranted.

PMID: 16013911 [PubMed – as supplied by publisher] Med J Aust. 2005 Jun 20;182(12):627-32.

Effectiveness of treatments for depression in older people.

Frazer CJ, Christensen H, Griffiths KM.

Centre for Mental Health Research, Australian National University, Canberra, ACT
0200, Australia. cathy.frazer@anu.edu.au.

OBJECTIVE: To conduct a systematic review of the evidence for the effectiveness
of a range of possible treatments for depression in older people. DATA SOURCES:
Literature search using the PubMed, PsycInfo and Cochrane Library databases.
DATA SYNTHESIS: Treatments that have been suggested to be effective for
depression were grouped under three categories: medical treatments,
psychological treatments, and lifestyle changes/alternative treatments. We
describe each treatment, review the studies of its effectiveness in people aged
>/= 60 years, and give a rating of the level of evidence. CONCLUSIONS: The
treatments with the best evidence of effectiveness are antidepressants,
electroconvulsive therapy, cognitive behaviour therapy, psychodynamic
psychotherapy, reminiscence therapy, problem-solving therapy, bibliotherapy (for
mild to moderate depression) and exercise. There is limited evidence to support
the effectiveness of transcranial magnetic stimulation, dialectical behaviour
therapy, interpersonal therapy, light therapy (for people in nursing homes or
hospitals), St John’s wort and folate in reducing depressive symptoms.

PMID: 15963019 [PubMed – in process] Clin Neurophysiol. 2005 May;116(5):1062-71.

Repetitive transcranial magnetic stimulation (rTMS) at high and low frequency:
an efficacious therapy for major drug-resistant depression?

Miniussi C, Bonato C, Bignotti S, Gazzoli A, Gennarelli M, Pasqualetti P, Tura
GB, Ventriglia M, Rossini PM.

IRCCS San Giovanni di Dio-FBF, Brescia, Italy. c.miniussi@oh-fbf.it

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is proposed for
the treatment of drug-resistant depression. Studies performed in accordance with
evidence-based medicine (EBM) are scarce, particularly in seeking optimal
treatment and evaluation parameters. We aimed to test various types of rTMS in a
large sample of depressed patients following EBM rules and to investigate
treatment-related changes in plasma levels of neurotransmitters involved in
depression. METHODS: Seventy-one drug-resistant depressed patients were randomly
assigned to low (1 Hz) or high (17 Hz) rate TMS, applied for 5 days over the
left dorsolateral prefrontal cortex (L-DLPFC). Patients were separated into two
study designs. One group (20 patients) received only active treatment, while the
other entered a double-blind, placebo-controlled, crossover design. Pre- and
post-treatment blood samples were taken for evaluation of plasma levels of
dopamine and serotonin. RESULTS: After a week of treatment patients had a
measurable benefit. However, overall the placebo stimulation did not differ
significantly from real stimulation, nor were differences observed between the
two rates of rTMS. The only difference emerged when the real stimulation was
applied at 17 Hz following placebo treatment. Plasma levels of neurotransmitters
between active and placebo rTMS were similar. CONCLUSIONS: Using the treatment
schedule of 1 week, although a clinical improvement after active treatment was
indeed observed, this was both clinically and biochemically indistinguishable
from that seen in the placebo arm. SIGNIFICANCE: This suggests that most of the
previous emphasis, for short period of treatment, should be tempered down and
that further work is required in order to verify whether optimal stimulation and
evaluation parameters for TMS-treatment of depression beyond the placebo effect
may be found following EBM rules.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15826846 [PubMed – indexed for MEDLINE] Dtsch Med Wochenschr. 2005 Apr 8;130(14):889-92.

[A new method for the treatment of depression: repetitive transcranial magnetic
stimulation] [Article in German]

Cordes J, Mobascher A, Arends M, Agelink MW, Klimke A.

Klinik und Poliklinik fur Psychiatrie und Psychotherapie der
Heinrich-Heine-Universitat Dusseldorf. cordes@uni-duesseldorf.de

Recent data suggest that repetitive transcranial magnetic stimulation (rTMS) is
effective in treating depressive symptoms to a lesser extent compared with
classical electroconvulsive therapy. However, rTMS represents an economical and
well tolerable procedure in relation to the expenditure of electroconvulsive
therapy with anaesthesia. Usually, rTMS is applicated as an add-on-therapy
accompanying psychopharmacological treatment. So far, it has predominantly been
used for patients with long-standing and so called treatment-refractory
symptoms. However, even in the early phase of a depressive episode rTMS would be
possibly more effective. In many cases, the standard procedure-application of up
to 10 rTMS-sessions will not be enough to produce therapeutic benefit. Therefore
rTMS series including up to 20 sessions are recommended. Long-term studies are
needed to clarify the role of rTMS for relapse prevention and to determine the
optimal frequency and duration of rTMS in such an indication. Although numerous
results of newer studies suggest a moderate antidepressive effect of rTMS, its
application in daily clinical routine practice cannot be recommended yet.
Larger, accurate designed and controlled studies, especially involving patients
of old age, are needed to evaluate the true tolerability and effectiveness of
rTMS as a new treatment option for depressive symptoms.

PMID: 15800823 [PubMed – indexed for MEDLINE] J Psychiatry Neurosci. 2005 Mar;30(2):91-7.

Comment in:
J Psychiatry Neurosci. 2005 Mar;30(2):81-2.

A framework for targeting alternative brain regions with repetitive transcranial
magnetic stimulation in the treatment of depression.

Schutter DJ, van Honk J.

Affective Neuroscience Section, Helmholtz Research Institute, Utrecht
University, Utrecht, The Netherlands. d.schutter@fss.uu.nl

It has been argued that clinical depression is accompanied by reductions in
cortical excitability of the left prefrontal cortex (PFC). In support of this,
repetitive transcranial magnetic stimulation (rTMS), which is a method of
enhancing cortical excitability, has shown antidepressant efficacy when applied
over the left PFC, although the overall therapeutic effects remain inconclusive.
The cerebral pathophysiology of depression is, however, not limited to
dysfunctions in the PFC, thus, targeting alternative brain regions with rTMS may
provide new therapeutic windows in the treatment of depression. Evidence from
electroencephalography and lesion studies suggests that not only is the left PFC
involved in depression but also the parietal cortex and cerebellum. Furthermore,
rTMS over the parietal cortex and the cerebellum has been found to improve mood
and emotional functioning, at least in healthy volunteers. We have integrated
these findings in an rTMS-oriented theoretical framework for the neurobiology of
low mood and depression. To establish the possible therapeutic efficacy of this
model, whereby, for example, the application of slow rTMS over the right
parietal cortex and fast rTMS over the cerebellum may be beneficial in different
subtypes of depression, clinical rTMS studies that target the parietal cortex
and cerebellum are warranted.

Publication Types:

PMID: 15798784 [PubMed – indexed for MEDLINE] J Psychiatry Neurosci. 2005 Mar;30(2):83-90.

Comment in:
J Psychiatry Neurosci. 2005 Mar;30(2):81-2.

Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the
treatment of depression: a systematic review and meta-analysis.

Couturier JL.

Department of Psychiatry, University of Western Ontario, London, Ont.

OBJECTIVE: To systematically review the literature pertaining to rapid-rate
repetitive transcranial magnetic stimulation (rTMS) compared with sham therapy
for the treatment of a major depressive episode in order to arrive at
qualitative and quantitative conclusions about the efficacy of rapid-rate rTMS.
METHODS: MEDLINE, the Cochrane Library, the metaRegister of Controlled Trials
and abstracts from scientific meetings were searched for the years 1966 until
July 2003. The search terms “transcranial magnetic stimulation” and
“transcranial magnetic stimulation AND depression” were used. Eighty-seven
randomized controlled trials investigating the efficacy of rTMS were referenced
on MEDLINE. Nineteen of these involved treatment of a major depressive episode,
and these were reviewed. Six met more specific inclusion criteria including the
use of rapid-rate stimulation, application to the left dorsolateral prefrontal
cortex, evaluation with the 21-item Hamilton Rating Scale for Depression (HAM-D)
and use of an intent-to-treat analysis. Scores on the 21-item HAM-D after
treatment and standard deviations were extracted from each article for treatment
and control subjects. A random-effects model was chosen for the meta-analysis,
and the weighted mean difference was used as a summary measure. RESULTS: Six
studies that met the inclusion criteria were identified and included in the
meta-analysis. Two of these reported a significantly greater improvement in mood
symptoms in the treatment versus the sham group. When combined in the
meta-analysis, the overall weighted mean difference was -1.1 (95% confidence
interval -4.5 to 2.3), and the results of a test for heterogeneity were not
significant (chi2(5) = 5.81, p = 0.33). CONCLUSIONS: This meta-analysis suggests
that rapid-rate rTMS is no different from sham treatment in major depression;
however, the power within these studies to detect a difference was generally
low. Randomized controlled trials with sufficient power to detect a clinically
meaningful difference are required.

Publication Types:

PMID: 15798783 [PubMed – indexed for MEDLINE] J Neurol Neurosurg Psychiatry. 2005 Apr;76(4):527-33.

Mirtazapine increases cortical excitability in healthy controls and epilepsy
patients with major depression.

Munchau A, Langosch JM, Gerschlager W, Rothwell JC, Orth M, Trimble MR.

Sobell Department of Motor Neuroscience and Movement Disorders, Dept. of
Clinical and Experimental Epilepsy, Institute of Neurology, National Hospital
for Neurology and Neurosurgery, Queen Square, London, UK.

BACKGROUND: Epilepsy is often complicated by depression requiring antidepressant
treatment. Such treatment might be proconvulsive. OBJECTIVE: To examine the
effects of the noradrenergic and specific serotonergic antidepressant
mirtazapine on motor cortex excitability in epilepsy patients with depression
and in healthy controls, using transcranial magnetic stimulation (TMS). METHODS:
Seven clinically depressed epilepsy patients treated with anticonvulsant drugs
and six healthy volunteers were studied. Before intake of mirtazapine and 24
hours afterwards (and also three weeks afterwards in the patients), the active
and resting motor threshold (AMT, RMT), the size of the motor evoked potential
(MEP), the cortical silent period (SP), and intracortical
inhibition/facilitation and intracortical facilitatory I wave interactions were
determined using single and paired pulse TMS. RESULTS: At baseline, AMT and RMT
were higher (p = 0.049 and p = 0.04, respectively) and the ratio SP duration/MEP
area greater in patients (p = 0.041). In patients but not in healthy subjects
AMT was lower 24 hours after intake of mirtazapine (p = 0.028). Mirtazapine had
no significant effect on the MEP size, duration of the SP, or the ratio of SP
duration to MEP size in patients. The duration of the SP was longer (p = 0.037)
but the ratio of SP duration to MEP size remained similar in healthy subjects
after mirtazapine. There were no significant differences in paired pulse
measures between the two groups either at baseline or after mirtazapine.
CONCLUSIONS: Mirtazapine increased neuronal excitability of pyramidal tract
axons in an activated state in both healthy controls and epilepsy patients with
major depression.

PMID: 15774440 [PubMed – indexed for MEDLINE] Health Technol Assess. 2005 Mar;9(9):1-156, iii-iv.

Clinical and cost-effectiveness of electroconvulsive therapy for depressive
illness, schizophrenia, catatonia and mania: systematic reviews and economic
modelling studies.

Greenhalgh J, Knight C, Hind D, Beverley C, Walters S.

Nuffield Institute for Health, University of Leeds, UK.

OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of
electroconvulsive therapy (ECT) for depressive illness, schizophrenia, catatonia
and mania. DATA SOURCES: Electronic bibliographic databases. The reference lists
of relevant articles and health services research-related resources were
consulted via the Internet. REVIEW METHODS: Identified studies were examined to
ascertain whether they met the inclusion criteria for the review. The study
quality of relevant articles was assessed using standard checklists and data
were abstracted using standardised forms into a database. Where relevant,
results from studies were pooled for meta-analysis. Two economic models were
developed primarily based on evidence from the clinical effectiveness analysis
and limited quality of life studies. RESULTS: Two good-quality systematic
reviews of randomised evidence of the efficacy and safety of ECT in people with
depression, schizophrenia, catatonia and mania were identified. Four systematic
reviews on non-randomised evidence were also identified, although only one of
these could be described as good quality. There was no randomised evidence of
the effectiveness of ECT in specific subgroups including older people, children
and adolescents, people with catatonia and women with postpartum exacerbations
of depression or schizophrenia. The economic modelling results for depression
did not demonstrate that any of the scenarios had a clear economic benefit over
the others, mainly because of the uncertainty surrounding the clinical
effectiveness of the different treatments and the quality of life utility gains.
Sensitivity analysis surrounding the cost of ECT and the quality of life utility
values had little effect on the overall results. The results of the model for
schizophrenia adapted to include ECT suggest that clozapine is a cost-effective
treatment compared with ECT. For patients who fail to respond to clozapine, ECT
treatment may be preferred to the comparative treatment of
haloperidol/chlorpromazine. CONCLUSIONS: Real ECT is probably more effective
than sham ECT, but as stimulus parameters have an important influence on
efficacy, low-dose unilateral ECT is no more effective than sham ECT. ECT is
probably more effective than pharmacotherapy in the short term and limited
evidence suggests that ECT is more effective than repetitive transcranial
magnetic stimulation. Tricyclic antidepressants (TCAs) may improve the
antidepressant effect of ECT during the course of treatment. Continuation
pharmacotherapy with TCAs combined with lithium in people who have responded to
ECT reduces the rate of relapses. Overall, gains in the efficacy of the
intervention depending on the stimulus parameters of ECT are achieved only at
the expense of an increased risk of cognitive side-effects. Limited evidence
suggests these effects do not last beyond 6 months, but there is no evidence
examining the longer term cognitive effects of ECT. There is little evidence of
the long-term efficacy of ECT. ECT either combined with antipsychotic medication
or as a monotherapy is not more effective than antipsychotic medication in
people with schizophrenia. More research is needed to examine the long-term
efficacy of ECT and the effectiveness of post-ECT pharmacotherapy, the
short-term and longer term cognitive side-effects of ECT, and the impact of ECT
on suicide and all-cause mortality. Further work is needed to examine the
information needs of people deciding whether to accept ECT and how their
decision-making can be facilitated. More research is also needed on the
mechanism of action of ECT. Finally, the quality of reporting of trials in this
area would be vastly improved by strict adherence to the Consolidated Standards
of Reporting Trials recommendations. Economic analysis may identify areas in
which research would be best targeted by identifying parameters where reducing
the level of uncertainty would have the most effect in helping to make the
decision on whether ECT is a cost-effective treatment.

Publication Types:

PMID: 15774232 [PubMed – indexed for MEDLINE] Curr Pain Headache Rep. 2005 Apr;9(2):87-9.

Transcranial magnetic stimulation for central pain.

Canavero S, Bonicalzi V.

Turin Advanced Neuromodulation Group, Via Morazzone 21,Torino 10132, Italy.

Transcranial magnetic stimulation recently has emerged as a therapeutic tool in
neurology and psychiatry, with contradictory results. Central pain, a major
chronic pain syndrome affecting millions of people worldwide, has been the focus
of a few studies. Although transcranial magnetic stimulation has no role in the
chronic management of such pain, it has potential as a screening procedure for
the much more effective extradural cortical stimulation, a minimally invasive
neurosurgical procedure that has emerged as the technique of choice in treating
these patients.

Publication Types:
Review, Tutorial

PMID: 15745616 [PubMed – indexed for MEDLINE] Australas Psychiatry. 2004 Sep;12(3):234-8.

Repetitive transcranial magnetic stimulation and electroconvulsive therapy:
complementary or competitive therapeutic options in depression?

Fitzgerald P.

Alfred Psychiatry Research Centre, Alfred and Monash University Department of
Psychological Medicine, Vic., Australia. paul.fitzgerald@med.monash.edu.au

OBJECTIVE: To examine issues pertaining to the potential clinical roles of
repetitive transcranial magnetic stimulation (rTMS) and the relationship of
these to the use of electroconvulsive therapy (ECT). METHODS: A review of
studies was carried out comparing the use of rTMS and ECT, with consideration of
issues relating to the populations in which rTMS may be applied. RESULTS: There
have been a number of randomized comparisons of rTMS and ECT. There are
limitations with these studies, but in general they indicate that in
non-psychotic patients rTMS appears to have a similar rate of response to ECT
and certainly seems to have meaningful clinical effects. There are a number of
clinical subpopulations in whom rTMS, but not ECT, is suitable, and assessment
of the effectiveness of TMS in these populations is required. CONCLUSIONS:
Repetitive TMS and ECT are likely to prove to be complementary clinical tools
and the introduction of clinical programmes with rTMS will enhance patient
options rather than replace the use of ECT.

PMID: 15715781 [PubMed – indexed for MEDLINE] Neuropsychopharmacology. 2005 Jun;30(6):1181-6.

Plasma concentrations of neuroactive steroids before and after electroconvulsive
therapy in major depression.

Baghai TC, di Michele F, Schule C, Eser D, Zwanzger P, Pasini A, Romeo E,
Rupprecht R.

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University of
Munich, Munich, Germany.

There is evidence that both cerebrospinal fluid (CSF) and plasma concentrations
of 3alpha-reduced neuroactive steroids are decreased in major depressive
disorder. Successful antidepressant pharmacotherapy, for example, with selective
serotonin reuptake inhibitors (SSRIs), over several weeks is accompanied by an
increase in CSF and plasma concentrations of these neuroactive steroids.
However, no such increase has been observed during nonpharmacological treatments
such as partial sleep deprivation or repetitive transcranial magnetic
stimulation. In order to investigate whether concentration changes in
neuroactive steroids are an important component of clinically effective
antidepressant treatment, we examined plasma concentrations of the neuroactive
steroids 3alpha,5alpha-tetrahydroprogesterone,
3alpha,5beta-tetrahydroprogesterone, 3beta,5alpha-tetrahydroprogesterone, and
their precursors progesterone, 5alpha-dihydroprogesterone, and
5beta-dihydroprogesterone in 31 pharmacotherapy-resistant depressed in-patients
before and after unilateral electroconvulsive therapy (ECT) as a monotherapy
over 4 weeks. Samples were quantified for neuroactive steroids by means of a
highly sensitive and specific combined gas chromatography/mass spectrometry
analysis. In all, 51.6% of the patients were treatment responders. There was no
influence of ECT on the plasma concentrations of any neuroactive steroid
studied. Moreover, neuroactive steroid levels did not differ between treatment
responders and nonresponders. Our study shows that changes in neuroactive
steroid plasma levels are not a mandatory factor for successful antidepressant
treatment by ECT. Thus, the previously observed changes in plasma concentrations
of neuroactive steroids following treatment with antidepressants such as SSRIs
more likely reflect distinct pharmacological properties of these compounds
rather than clinical improvement.

Publication Types:
Clinical Trial

PMID: 15702138 [PubMed – indexed for MEDLINE] Psychol Med. 2004 Oct;34(7):1157-63.

High-frequency repetitive transcranial magnetic stimulation in schizophrenia: a
combined treatment and neuroimaging study.

Hajak G, Marienhagen J, Langguth B, Werner S, Binder H, Eichhammer P.

Department of Psychiatry and Psychotherapy, University of Regensburg,
Regensburg, Germany. goeran.hajak@medbo.de

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of frontal brain
regions is under study as a non-invasive method in the treatment of affective
disorders. Recent publications provide increasing evidence that rTMS may be
useful in treating schizophrenia. Results are most intriguing, demonstrating a
reduction of negative symptoms following high-frequency rTMS. In this context,
disentangling of negative and depressive symptoms is of the utmost importance
when understanding specific rTMS effects on schizophrenic symptoms. METHOD:
Using a sham-controlled parallel design, 20 patients with schizophrenia were
included in the study. Patients were treated with high-frequency 10 Hz rTMS over
10 days. Besides clinical ratings, ECD-SPECT (technetium-99 bicisate single
photon emission computed tomography) imaging was performed before and after
termination of rTMS treatment. RESULTS: High-frequency rTMS leads to a
significant reduction of negative symptoms combined with a trend for
non-significant improvement of depressive symptoms in the active stimulated
group as compared with the sham stimulated group. Additionally, a trend for
worsening of positive symptoms was observed in the actively treated
schizophrenic patients. In both groups no changes in regional cerebral blood
flow could be detected by ECD-SPECT. CONCLUSIONS: Beneficial effects of
high-frequency rTMS on negative and depressive symptoms were found, together
with a trend for worsening positive symptoms in schizophrenic patients.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15697042 [PubMed – indexed for MEDLINE] Nervenarzt. 2005 Jan;76(1):28-35.

[Vagus nerve stimulation, repetitive transcranial magnetic stimulation, and
electroconvulsive therapy in the treatment of depressive disorders] [Article in German]

Bajbouj M, Heuser I.

Klinik und Poliklinik fur Psychiatrie und Psychotherapie,
Charite-Universitatsmedizin Berlin. malek.bajbouj@charite.de

Affective disorders, especially major depression, are the most common
psychiatric disorders. Although well treatable, a number of patients do not or
do not sufficiently respond to antidepressant pharmacotherapy. Therefore there
is a need for safe and efficient alternative therapeutic strategies.
Neurostimulatory therapies such as electroconvulsive therapy, repetitive
transcranial magnetic stimulation, and vagus nerve stimulation belong to these
alternatives. In this article we review their mechanisms of action and summarize
efficacy and adverse effects.

PMID: 15666168 [PubMed – indexed for MEDLINE] Clin Neurophysiol. 2005 Feb;116(2):386-92.

Effect of electroconvulsive therapy on cortical excitability in patients with
major depression: a transcranial magnetic stimulation study.

Chistyakov AV, Kaplan B, Rubichek O, Kreinin I, Koren D, Hafner H, Feinsod M,
Klein E.

Laboratory of Clinical Neurosciences, Department of Neurosurgery, Rambam
(Maimonides) Medical Center, B. Rappaport Faculty of Medicine, The Technion,
Israel Institute of Technology, Haifa, Israel. a_chistyakov@rambam.health.gov.il

OBJECTIVE: The antidepressant action of electro-convulsive therapy (ECT) and
repetitive transcranial magnetic stimulation (rTMS) may be related to their
ability to modulate cortical excitability. The aim of this study was to
investigate changes in cortical excitability following ECT in patients with
major depression (MD) and to compare therapeutic efficacy of ECT combined with
rTMS to that of ECT alone. METHODS: Twenty-two patients with MD were assigned to
receive ECT and right prefrontal 1 Hz rTMS (n=12) or ECT with sham rTMS (n=10).
ECT was given twice weekly and rTMS was applied on the remaining 4 days,
throughout 3 weeks. The resting motor threshold (rMT) and motor evoked potential
(MEP)/M-wave area ratio were evaluated before and 6 h after the first, third and
sixth ECT session. The active motor threshold (aMT), intra-cortical inhibition
(ICI) and intra-cortical facilitation (ICF) were measured at baseline and 24 h
after the last ECT. RESULTS: There were no significant differences in the degree
of clinical improvement and measures of cortical excitability in the ECT+active
rTMS group as compared to the ECT+sham rTMS group. Marked clinical improvement
observed in 19 out of the 22 patients was associated with a significant increase
of the MEP/M-wave area ratio, decrease of the aMT and reduction of the ICI in
the left hemisphere. CONCLUSIONS: The antidepressant effect of ECT was
associated with an enhancement of left hemispheric excitability. rTMS did not
add to the beneficial effect of ECT. However, the small sample size and the
robust effect of ECT might have obscured a potential therapeutic effect of rTMS.
SIGNIFICANCE: Measures of cortical excitability may provide insight to our
understanding of the mechanism of action of ECT and might be useful for the
assessment of treatment response.

Publication Types:
Clinical Trial
Controlled Clinical Trial

PMID: 15661116 [PubMed – indexed for MEDLINE] Biol Psychiatry. 2005 Jan 15;57(2):162-6.

Transcranial magnetic stimulation accelerates the antidepressant effect of
amitriptyline in severe depression: a double-blind placebo-controlled study.

Rumi DO, Gattaz WF, Rigonatti SP, Rosa MA, Fregni F, Rosa MO, Mansur C,
Myczkowski ML, Moreno RA, Marcolin MA.

Institute of Psychiatry, University of Sao Paulo, Faculty of Medicine, Sao
Paulo-SP, Brazil. drumi@usp.br

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive method to
stimulate the cortex, and the treatment of depression is one of its potential
therapeutic applications. Three recent meta analyses strongly suggest its
benefits in the treatment of depression. The present study investigates whether
repetitive TMS (rTMS) accelerates the onset of action and increases the
therapeutic effects of amitriptyline. METHODS: Forty-six outpatients meeting
DSM-IV criteria for nonpsychotic depressive episode were randomly assigned to
receive rTMS (n = 22) or sham repetitive TMS (sham) (n = 24) during 4 weeks over
dorsolateral prefrontal cortex (DLPFC) in this double-blind controlled trial.
All patients were concomitantly taking amitriptyline (mean dose 110 mg/d). The
rTMS group received 20 sessions (5 sections per week) of 5 Hz rTMS (120% of
motor threshold and 1250 pulses per session). Sham stimulation followed the same
schedule, however, using a sham coil. The efficacy variables were the Hamilton
Depression Rating Scale-17 items (HAM-D/17), the Montgomery-Asberg Depression
Rating Scale (MADRS), a Visual Analogue Scale (VAS), and the Clinical Global
Impression (CGI). Tolerability was assessed by clinical examination and a safety
screening of TMS side effects. RESULTS: Repetitive TMS had a significantly
faster response to amitriptyline. There was a significant decrease in HAM-D/17
scores, already after the first week of treatment (p < .001 compared with
baseline and p < .001 compared with sham). The decrease in HAM-D/17 scores in
the rTMS group was significantly superior compared with the sham group
throughout the study (p < .001 at fourth week). CONCLUSIONS: Repetitive TMS at 5
Hz accelerated the onset of action and augmented the response to amitriptyline.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15652875 [PubMed – indexed for MEDLINE] Bull Acad Natl Med. 2004;188(6):999-1007; discussion 1007-10.

[Depression and aging] [Article in French]

Loo H, Gallarda T, Fabre I, Olie JP.

Service Hospitalo-Universitaire de Sante Mentale et de Therapeutique, CH
Sainte-Anne, 1 rue Cabanis, 75674 Paris 14.

Depression is one of the most common health disorders in elderly people. It is
still often considered as a natural consequence of aging, arising in reaction to
a medical disease, cognitive or functional decline, or a loss of social fabric.
Many studies have highlighted the low rates of diagnosis and treatment of
depression, especially in the primary care setting. Major depression in old age
is characterized by the same core symptoms as in other periods of life. However,
aging may accentuate some symptoms and alleviate others. Somatic concern, marked
anxiety, poor subjective memory, psychotic ideation, and recurrent thoughts of
death can mask sadness and anhedonia. Organic factors and adverse life events
are often intricately linked with the pathogenesis of depressive states in the
elderly. The role of cerebrovascular lesions has also been established,
particularly in late-onset depressive disorders. The management of depressive
disorders in older people, as in younger adults, involves pharmacological and
psychological treatments. Electroconvulsive therapy can be beneficial in some
cases. Transcranial magnetic stimulation is being evaluated in this setting.

Publication Types:
Review, Tutorial

PMID: 15651428 [PubMed – indexed for MEDLINE] Child Adolesc Psychiatr Clin N Am. 2005 Jan;14(1):193-210, viii-ix.

Electroconvulsive therapy and repetitive transcranial magnetic stimulation in
children and adolescents: a review and report of two cases of epilepsia
partialis continua.

Morales OG, Henry ME, Nobler MS, Wassermann EM, Lisanby SH.

Magnetic Brain Stimulation Laboratory, Department of Biological Psychiatry, New
York State Psychiatric Institute, 1051 Riverside Drive, Box 126, New York, NY
10032-2695, USA. om2102@columbia.edu

Brain stimulation for the treatment of psychiatric disorders has received
increasing attention over the past decade. The introduction of experimental
means to stimulate the brain noninvasively with magnetic fields not only has
raised interest in these novel means of modulating brain activity but also has
refocused attention on a mainstay in the treatment of severe major depression
and other disorders (electroconvulsive therapy). This article reviews the
current state of knowledge concerning the use electroconvulsive therapy,
repetitive transcranial magnetic stimulation, and magnetic seizure therapy in
children and adolescents. Two cases of medically intractable epilepsia partialis
continua are presented to add to the limited literature on the use of repetitive
transcranial magnetic stimulation in children and adolescents and illustrate the
concept of using functional neuroimaging results to target the application of a
focal intervention in an attempt to dampen hyperactive regions of the cortex.

Publication Types:
Case Reports
Review, Tutorial

PMID: 15564059 [PubMed – indexed for MEDLINE]

Child Adolesc Psychiatr Clin N Am. 2005 Jan;14(1):1-19, v.
Emerging brain-based interventions for children and adolescents: overview and
clinical perspective.

Hirshberg LM, Chiu S, Frazier JA.

The NeuroDevelopment Center, 260 West Exchange Street, Suite 302, Providence, RI
02903, USA. lhirshberg@neruodevelopmentcenter.com

Electroencephalogram biofeedback (EBF), repetitive transcranial magnetic
stimulation (rTMS), and vagal nerve stimulation (VNS) are emerging interventions
that attempt to directly impact brain function through neurostimulation and
neurofeedback mechanisms. This article provides a brief overview of each of
these techniques, summarizes the relevant research findings, and examines the
implications of this research for practice standards based on the guidelines for
recommending evidence based treatments as developed by the American Academy of
Child and Adolescent Psychiatry for attention deficit hyperactivity disorder
(ADHD). EBF meets the “Clinical Guidelines” standard for ADHD, seizure
disorders, anxiety, depression, and traumatic brain injury. VNS meets this same
standard for treatment of refractory epilepsy and meets the lower “Options”
standard for several other disorders. rTMS meets the standard for “Clinical
Guidelines” for bipolar disorder, unipolar disorder, and schizophrenia. Several
conditions are discussed regarding the use of evidence based thinking related to
these emerging interventions and future directions.

Publication Types:
Review, Tutorial

PMID: 15564050 [PubMed – indexed for MEDLINE] Encephale. 2004 Jul-Aug;30(4):363-8.

[Transcranial magnetic stimulation in cognition and neuropsychology] [Article in French]

Verdon CM, Saba G, Januel D.

Unite de Recherche Clinique Romain-Rolland, EPS Ville-Evrard (Secteur 3), 5, rue
du Docteur Delafontaine, 93200 Saint-Denis.

Classical neuropsychology relies on patients with irreversible brain lesions and
cognitive impairments give informations about normal brain function.
Transcranial Magnetic Stimulation (TMS) is a non-invasive method which involves
placing an electromagnetic coil on the scalp. A pulse generates a magnetic field
and this one passes, unattenuated by the skin and scalp, into the cortex
inducing a current which results in neural activity. The technique shows a good
temporal resolution and, moreover, because it represents an interference
technique, can be said to have excellent functional resolution. For this reason,
TMS appears to be a new tool for research in neuropsychology, producing
transitory ‘virtual lesion’effects which could help to understand how, when and
where cognitive tasks are performed. The purpose of this article is to review
recent research using TMS in cognition and neuropsychology, in a non exhaustive
way. In safety studies, single TMS over motor cortex can produce simple
movements. Several groups have applied TMS to the study of visual processing and
found an impaired detection of visual stimuli. In a same way, TMS can disrupt
speech when it was delivered in the language dominant hemisphere. Studies on the
memory effects of TMS have been conflicting and the results seem to depend on
the choice of paradigm and parameters. Other study depicted improvements in
executive functioning after TMS on the left middle frontal gyrus or a diminution
in reaction time during an analogic reasoning task. Moreover, some facial
emotions seem to be less recognizable after TMS. Although TMS seem to be a new
tool for neuro-psychological investigations in healthy subjects, few studies
reported cognitive effects of rTMS treatment in psychiatry. In a therapeutic
view, many of these trials have supported a significant effect of TMS, but in
some studies the effect is small and short lived. Several groups have reported
on the use of rTMS as a treatment in resistant major depression and the impact
on cognition functioning. Most of results tend to find no adverse cognitive
effects after several weeks of daily rTMS in depressed patients, compared to
Electroconvulsivo-therapy (ECT). The effects of transcranial magnetic
stimulation (TMS) on hallucination severity and neurocognition were studied in a
recent study. A statistically significant improvement was observed on a
hallucination scale and on one cognitive measure. TMS is a promising tool for
cognitive neuroscience and can provide complementary information to the one
obtained using neuropsychological tests, and the one obtained using functional
imaging techniques, which have superior spatial but inferior temporal

PMID: 15538312 [PubMed – indexed for MEDLINE] Rev Bras Psiquiatr. 2004 Jun;26(2):100-2. Epub 2004 Oct 27.

[Transcranial Magnetic Stimulation in depression: results of bi-weekly
treatment] [Article in Portuguese]

Boechat-Barros R, Brasil-Neto JP.

Laboratorio de Neurociencias e Comportamento, Departamento de Ciencias
Fisiologicas, Instituto de Biologia, Universidade de Brasilia, DF, Brazil.

OBJECTIVE: Transcranial Magnetic Stimulation (TMS) has been shown to be a useful
therapy for depression. This paper evaluates the results of bi-weekly
low-frequency TMS of 4 weeks duration, in 10 patients with depression who do not
respond or are intolerant to antidepressive medication. METHODS: This is a case
series study. DMS-IV criteria were used to diagnose depression. In order to
disclose possible improvements in depressive symptoms, the 17 items Hamilton
scale was used at three different moments: at the beginning, middle and end of
the treatment period. Results were analysed using Friedman’s chi2 test. RESULTS:
Hamilton’s scale score improvement was > 50% in five patients and > 75% in 3 of
these. CONCLUSIONS: TMS may be efficacious, safe and easily performed as an
adjunct to medical treatment of depression. We cannot differentiate a
potentiation of the effect of antidepressive medication from an intrinsic effect
of TMS alone, since we did not treat any subjects without the concurrent use of

PMID: 15517060 [PubMed – in process] J Clin Psychiatry. 2004 Oct;65(10):1323-8.

Comment in:
J Clin Psychiatry. 2005 Apr;66(4):543; author reply 543-4.

A 3-month, follow-up, randomized, placebo-controlled study of repetitive
transcranial magnetic stimulation in depression.

Koerselman F, Laman DM, van Duijn H, van Duijn MA, Willems MA.

Department of Psychiatry, St. Lucas Andreas Hospital, Amsterdam, The
Netherlands. f.koerselman@slaz.nl

BACKGROUND/OBJECTIVE: There is evidence for an antidepressant effect of
repetitive transcranial magnetic stimulation (rTMS), but little is known about
posttreatment course. Therefore, we conducted a placebo-controlled, double-blind
study in depressed patients in order to investigate the effect of rTMS on
depression over 12 weeks after completion of the 2-week stimulation period.
METHOD: 55 patients with a moderate or severe DSM-IV major depressive episode
were randomly assigned to rTMS or sham treatment. rTMS was given daily for 10
days over the left dorsolateral prefrontal cortex with the following treatment
parameters: 20 Hz, 20 trains of 2 seconds, 30 seconds between trains, and 80%
motor threshold. The effect of rTMS on depression was rated repeatedly with the
17-item Hamilton Rating Scale for Depression (HAM-D) during the 2-week period of
stimulation and the 12-week follow-up period conducted from 1997 to 2001.
RESULTS: We found a modest, clinically nonrelevant decrease in HAM-D scores in
both rTMS and sham patients over 2 weeks of treatment. However, over the
subsequent 12-week follow-up, the rTMS group continued to improve significantly
compared with the placebo group. CONCLUSION: Decrease of depressive symptoms may
continue after the cessation of rTMS stimulation.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15491234 [PubMed – indexed for MEDLINE] J Affect Disord. 2004 Oct 1;82(1):71-6.

Motor cortical excitability and clinical response to rTMS in depression.

Fitzgerald PB, Brown TL, Marston NA, Daskalakis ZJ, de Castella A, Bradshaw JL,
Kulkarni J.

Alfred Psychiatry Research Center, The Alfred and Monash University, Department
of Psychological Medicine, Level 2, Old Baker Building, Commercial Road,
Melbourne, Vic. 3004, Australia. paul.fitzgerald@med.monash.edu.au
BACKGROUND: The relationship between frontal lobe activity in the left and right
hemispheres and the pathophysiology of depression remains unclear. In addition,
it is uncertain whether levels of frontal or motor cortical excitability relate
to clinical response to treatment modalities. We aimed to explore whether motor
cortical excitability as assessed with single and paired pulse transcranial
magnetic stimulation (TMS) could be used to predict the response to treatment
with repetitive TMS (rTMS) applied to the left or right prefrontal cortex.
METHODS: Motor thresholds, cortical excitability and cortical inhibition (CI)
were assessed prior to a trial of rTMS in patients with treatment resistant
depression. RESULTS: There was no consistent pattern of differences in
hemispheric activity, although there was a relationship between the degree of
psychopathology and cortical excitability (right hemisphere) and an inverse
relationship between inhibitory activity and clinical response (left
hemisphere). CONCLUSIONS: The study does not support a simple model of
laterality in motor cortical excitability in depression. The TMS measures used
in this study appear to be of limited use in the prediction of clinical response
to rTMS.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15465578 [PubMed – indexed for MEDLINE] Eur Psychiatry. 2004 Sep;19(6):382-3.

Repetitive transcranial magnetic stimulation does not potentiate antidepressant

Poulet E, Brunelin J, Boeuve C, Lerond J, D’Amato T, Dalery J, Saoud M.

EA 3092, Universite Claude Bernard Lyon 1, 69677 Bron cedex, France.

In a double blind controlled study, rTMS results in a similar antidepressant
effect to sham in combination with paroxetine. Both groups had the same delay in
scale’s scores improvement. rTMS seems not to be efficient as an add-on
treatment to pharmacological medication in non-resistant major depression.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15363481 [PubMed – indexed for MEDLINE] Int J Geriatr Psychiatry. 2004 Sep;19(9):833-42.

Antidepressant efficacy and cognitive effects of repetitive transcranial
magnetic stimulation in vascular depression: an open trial.

Fabre I, Galinowski A, Oppenheim C, Gallarda T, Meder JF, De Montigny C, Olie
JP, Poirier MF.

Sainte-Anne Hospital, University Department of Psychiatry, Paris, France.

BACKGROUND: Beneficial effects of repetitive transcranial magnetic stimulation
(rTMS) were demonstrated by many controlled studies in major depression.
Moreover, this promising and non invasive therapeutic tool seems to be better
tolerated than electroconvulsive therapy.Vascular depression is a subtype of
late-life depression, associated with cerebrovascular disease and means a poorer
response to antidepressant treatment. We employed rTMS over the left prefrontal
cortex in 11 patients with late-onset resistant vascular depression. The primary
purpose of this two-week open study was to examine antidepressant efficacy of
rTMS in vascular depression. The secondary aim was to evaluate cognitive effects
of rTMS in our sample. METHODS: Clinical status, as measured with the Hamilton
Depression Rating Scale (HDRS), and cognitive effects, as evaluated by
neuropsychological tests, were assessed at baseline and after two weeks of rTMS.
Brain measurements to obtain an index of prefrontal atrophy were performed at
both the motor cortex and prefrontal cortex. RESULTS: Five out of 11 resistant
patients with late-onset vascular depression were responders. They showed a
clinically meaningful improvement in HDRS scores, with a decrease of 11, 4
points (p<0.01). Antidepressant response is correlated to the relative degree of
prefrontal atrophy (p = 0.05). After two weeks, verbal fluency and visuospatial
memory improved. No cognitive performance deteriorated except for verbal memory,
as the delayed recall decreased significantly in the responders’ group.
CONCLUSIONS: Our preliminary observations prompt to perform a subsequent
controlled study to examine if rTMS may constitute an alternative to
electroconvulsive therapy.

Publication Types:
Clinical Trial

PMID: 15352140 [PubMed – indexed for MEDLINE] J Psychiatry Neurosci. 2004 Jul;29(4):268-79.

Transcranial magnetic stimulation (TMS) of the human frontal cortex:
implications for repetitive TMS treatment of depression.

Paus T, Barrett J.

Neuropsychology Department, Montreal Neurological Institute, McGill University,
Montreal, Que. tomas@bic.mni.mcgill.ca

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool used
to manipulate activity in specific neural circuits of the human brain. Clinical
studies suggest that, in some patients with major depression, rTMS has the
potential to alleviate symptoms that may be related to functional abnormalities
in a frontocingulate circuit. This paper reviews the rationale for the use of
rTMS in this context. The following topics are discussed: symptoms and cognition
in major depression, with special emphasis on the initiation of speech;
neuroimaging studies of depression; rTMS as treatment for depression; structure
and function of the mid-dorsolateral frontal and anterior cingulate cortices;
and combined TMS/positron emission tomography studies of frontocortical

Publication Types:

PMID: 15309043 [PubMed – indexed for MEDLINE] J Clin Psychiatry. 2004 Jun;65(6):772-82.

No deterioration of cognitive performance in an aggressive unilateral and
bilateral antidepressant rTMS add-on trial.

Hausmann A, Pascual-Leone A, Kemmler G, Rupp CI, Lechner-Schoner T,
Kramer-Reinstadler K, Walpoth M, Mechtcheriakov S, Conca A, Weiss EM.

Department of General Psychiatry, University Hospital Innsbruck, Austria.

BACKGROUND: Cognitive functions were assessed before and following a course of
repetitive transcranial magnetic stimulation (rTMS) in patients with depression
participating in a sham-controlled, randomized trial of rTMS as adjunct to
antidepressant treatment. METHOD: Forty-one medicated inpatients with a DSM-IV
diagnosis of a depressive episode were consecutively randomly assigned to 1 of 3
groups comparing 2 active rTMS conditions with sham stimulation. The rTMS was
applied either at high frequency over the left dorsolateral-prefrontal cortex
(DLPFC) (10 sessions x 10 trains x 10 seconds 20 Hz at 100% motor threshold
[MT], 90-second intertrain interval) or in a combined high- and low-frequency
manner to the left and right DLPFC, respectively (10 sessions x 1 train x 10
minutes at 120% MT). Thirty-eight patients completed a neuropsychological test
battery at baseline and following day 14. The cognitive assessment focused on
motor skills, attention, executive functions, learning, and memory. Data were
collected from November 1999 to August 2002. RESULTS: Active treatment groups
did not differ with respect to assessed cognitive measures and thus were pooled.
A comparison of short-term changes (baseline-day 14) in neuropsychological
performance revealed a more favorable time course of the actively treated
patients for encoding in the verbal memory test compared with the
sham-stimulated patients. CONCLUSIONS: Unilateral rTMS as well as bilateral
combined rTMS revealed no detrimental effects on cognition, as compared with the
sham group. Moreover, neither the add-on design nor the used aggressive
parameters had a negative impact on cognitive measures in comparison with sham.
Repetitive transcranial magnetic stimulation might have mild beneficial
cognitive effects partly independent of its antidepressant efficacy.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Review of Reported Cases

PMID: 15291654 [PubMed – indexed for MEDLINE] Depress Anxiety. 2004;19(4):249-56.

Safety and benefits of distance-adjusted prefrontal transcranial magnetic
stimulation in depressed patients 55-75 years of age: a pilot study.

Nahas Z, Li X, Kozel FA, Mirzki D, Memon M, Miller K, Yamanaka K, Anderson B,
Chae JH, Bohning DE, Mintzer J, George MS.

Brain Stimulation Laboratory, Institute of Psychiatry, Medical University of
South Carolina, Charleston, SC 29425, USA. nahasz@musc.edu

In contrast to the effects seen in younger adults, depressed elderly subjects
have shown more modest antidepressant responses to transcranial magnetic
stimulation (TMS). We theorized that higher stimulation intensities in older
depressed subjects with prefrontal atrophy might be needed to stimulate
underlying cortex. In an open design with patients on stable baseline
medications, we treated 18 treatment-resistant elderly depressed subjects (mean
age 61.2 +/- 7.3) with 15 rTMS sessions over 3 weeks. We adjusted the delivered
TMS intensity to account for MRI measured prefrontal atrophy. The skull to
prefrontal cortex distance increased with age, whereas the skull to motor cortex
distance did not. All subjects tolerated the higher doses well. The average
intensity used was 114% of motor threshold (MT) with a range from 103-141% MT.
There was an average 35% decline over the 3 weeks in HRSD scores. After 3 weeks
of treatment, 27% (5/18) met response criteria (> 50% improvement), with four of
these five also meeting criteria for remission (exit Hamilton Depression Score <
8). These initial pilot findings support the need for blinded studies using
prefrontal TMS in an elderly population, testing whether TMS, delivered at
stimulation intensities calculated to overcome atrophy, is more effective than
TMS without adjusting for atrophy.

Publication Types:
Clinical Trial

PMID: 15274174 [PubMed – indexed for MEDLINE] Biol Psychiatry. 2004 Aug 1;56(3):146-50.

Neurogenesis and depression: etiology or epiphenomenon?

Henn FA, Vollmayr B.

Central Institute of Mental Health, Mannheim, Germany.

The concept that decreased neurogenesis might be the cause of depression is
supported by the effects of stress on neurogenesis and the demonstration that
neurogenesis seems to be necessary for antidepressant action. Data from the
animal models tested to date show that decreasing the rate of neurogenesis does
not lead to depressive behavior. Furthermore, evidence shows that an effective
treatment for depression, transcranial magnetic stimulation, does not alter
rates of neurogenesis. On the basis of these findings, it is suggested that
neurogenesis might play a subtle role in depression but that it is not the
primary factor in the final common pathway leading to depression.

Publication Types:
Review, Tutorial

PMID: 15271582 [PubMed – indexed for MEDLINE] J Neurol Neurosurg Psychiatry. 2004 Aug;75(8):1171-4.

Repetitive transcranial magnetic stimulation is as effective as fluoxetine in
the treatment of depression in patients with Parkinson’s disease.

Fregni F, Santos CM, Myczkowski ML, Rigolino R, Gallucci-Neto J, Barbosa ER,
Valente KD, Pascual-Leone A, Marcolin MA.

Department of Neurology, Beth Israel Deaconess Medical Center and Harvard
Medical School, Boston, Massachusetts 02215, USA. ffregni@bidmc.harvard.edu

OBJECTIVE: To study the efficacy of 15 Hz repetitive transcranial magnetic
stimulation (rTMS) in treating depression in patients with Parkinson’s disease.
METHODS: 42 patients were enrolled into two groups: group 1, active rTMS (15 Hz
rTMS for 10 days) and placebo drug treatment; group 2, sham rTMS and fluoxetine
20 mg/day. A specially designed sham coil was used for sham stimulation. The
unified Parkinson’s disease rating scale (UPDRS), activities of daily living
(ADL), Hamilton rating scale for depression (HRSD), Beck depression inventory
(BDI), and mini-mental state examination (MMSE) were assessed by a rater blinded
to treatment arm. RESULTS: HRSD and BDI were improved to the same extent in both
groups after two weeks of treatment (38% and 32% for group 1, 41% and 33% for
group 2, respectively). At week 8 there was a tendency for worse motor UPDRS
scores in group 2 (NS). ADL showed improvement at week 8 only in group 1. MMSE
improved in both groups after treatment, but faster in group 1 than in group 2.
There were fewer adverse effects in group 1 than in group 2. CONCLUSIONS: rTMS
has the same antidepressant efficacy as fluoxetine and may have the additional
advantage of some motor improvement and earlier cognitive improvement, with
fewer adverse effects.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15258224 [PubMed – indexed for MEDLINE] CNS Spectr. 2004 Jun;9(6):476-82.

Decision analysis of the cost-effectiveness of repetitive transcranial magnetic
stimulation versus electroconvulsive therapy for treatment of nonpsychotic
severe depression.

Kozel FA, George MS, Simpson KN.

Brain Stimulation Laboratory, Department of Psychiatry, Medical University of
South Carolina, and Ralph H. Johnson Veterans Affairs Medical Center,
Charleston, USA. kozelfa@musc.edu

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a new
treatment with promise for resistant depression. OBJECTIVE: We tested the
economic feasibility of this new method compared with electroconvulsive therapy
(ECT). METHOD: An economic decision analysis was used to compare the costs of
three different treatment strategies for nonpsychotic severe depression. The
strategies were: ECT alone; rTMS alone; and rTMS followed by ECT for
nonresponders (rTMS-to-ECT). We calculated 12-month costs and quality adjusted
life years (QALYs) for the three treatment options for all nonpsychotic,
severely depressed United States patients who would have otherwise undergone
ECT. A sensitivity analysis was performed to test the degree of change in
outcome with various parameter changes. RESULTS: The additional cost of using
ECT alone compared with rTMS alone was 460,031 US dollars per quality adjusted
year of life gained. For ECT versus rTMS-to-ECT, there was both an increased
cost and a loss of 1,538 QALYs with ECT alone. The sensitivity analysis revealed
the model to be robust with various parameter changes. CONCLUSION: If rTMS were
to be made widely available clinically in the US, it would offer a substantial
economic benefit over ECT in treating resistant depression. Using rTMS-to-ECT
offers not only an economic advantage but also an increase in QALYs. This
analysis suggests that rTMS would be a cost-effective treatment for depression
compared with the current option of ECT alone.

PMID: 15162090 [PubMed – indexed for MEDLINE] Psychiatry Res. 2004 Apr 30;126(2):123-33.

Repetitive transcranial magnetic stimulation: a putative add-on treatment for
major depression in elderly patients.

Mosimann UP, Schmitt W, Greenberg BD, Kosel M, Muri RM, Berkhoff M, Hess CW,
Fisch HU, Schlaepfer TE.

Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne
NE4 6BE, UK.

Repetitive transcranial magnetic stimulation (rTMS) is a recent putative
treatment for affective disorders. Several studies have demonstrated
antidepressant effects of rTMS in younger patients; we aimed to assess its
effect in older outpatients with treatment-resistant major depression.
Twenty-four outpatients (mean age=62 years, S.D.=12) with major depression were
randomized for sham or real stimulation and received 10 daily rTMS sessions (20
Hz, 2-s trains, 28-s intertrain intervals, 100% of motor threshold) in addition
to the antidepressant medication. For sham stimulation, the coil was tilted 90
degrees. Depression severity was assessed using the Hamilton Depression Rating
Scale, the Beck Depression Inventory, items from the NIMH self-rated symptom
scale, and a visual analog depression scale. Mini-Mental Status Examination
performance, memory, and executive and attentional functions were measured to
control for cognitive side effects. Depression ratings revealed significant
antidepressant effects within 2 weeks in both sham and real stimulation groups;
however, there were no between-group differences. Treatment with rTMS was safe;
adverse events were rare and not more prevalent in either group, and cognitive
assessment did not show any deterioration. We were unable to demonstrate any
additional antidepressant effects of real stimulation in elderly patients with
treatment-resistant major depression. Therapeutic effects of rTMS in this
clinically challenging patient group remain to be demonstrated.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15123391 [PubMed – indexed for MEDLINE] Clin EEG Neurosci. 2004 Jan;35(1):4-13.

Current status of the utilization of antiepileptic treatments in mood, anxiety
and aggression: drugs and devices.

Barry JJ, Lembke A, Bullock KD.

Department of Psychiatry, Stanford University Medical Center, 401 Quarry Road MC
5723, Stanford, CA 94305, USA. jbarry@leland.stanford.edu

Interventions that have been utilized to control seizures in people with
epilepsy have been employed by the psychiatric community to treat a variety of
disorders. The purpose of this review will be to give an overview of the most
prominent uses of antiepileptic drugs (AEDs) and devices like the Vagus Nerve
Stimulator (VNS) and Transcranial Magnetic Stimulation (TMS) in the treatment of
psychiatric disease states. By far, the most prevalent use of these
interventions is in the treatment of mood disorders. AEDs have become a mainstay
in the effective treatment of Bipolar Affective Disorder (BAD). The U.S. Food
and Drug Administration has approved the use of valproic acid for acute mania,
and lamotrigine for BAD maintenance therapy. AEDs are also effectively employed
in the treatment of anxiety and aggressive disorders. Finally, VNS and TMS are
emerging as possibly useful tools in the treatment of more refractory depressive

Publication Types:

PMID: 15112459 [PubMed – indexed for MEDLINE] Eur Psychiatry. 2004 Apr;19(2):118-9.

ECT response after relapse during continuation repetitive transcranial magnetic
stimulation. A case report.

Conca A, Hrubos W, Di Pauli J, Konig P, Hausmann A.

Department of Psychiatry I, Regional Hospital of Rankweil, LKH Rankweil,
Valunastr. 16, Rankweil 6830, Austria. andreas.conca@lkhr.at

Research on repetitive transcranial magnetic stimulation (rTMS) indicates that
the treatment of non-psychotic depression is comparable to electroconvulsive
therapy (ECT) in terms of short-term outcome. We report on a woman who exerted a
recurrent moderate major depressive episode, 6 months after discontinuation of
maintenance ECT. She responded to acute rTMS treatment which was followed by the
rTMS maintenance-protocol. Within 2 months of continuation rTMS she relapsed
suffering from a severe non psychotic depressive episode and had to be switched
to a successful ECT. In this patient rTMS had a good clinical impact as an acute
treatment strategy, but failed to prevent relapse as the continuation ECT
previously did in the same patient.

Publication Types:
Case Reports

PMID: 15051113 [PubMed – indexed for MEDLINE] Neurosci Lett. 2004 Apr 1;358(3):193-6.

Slow repetitive transcranial magnetic stimulation increases somatosensory
high-frequency oscillations in humans.

Ogawa A, Ukai S, Shinosaki K, Yamamoto M, Kawaguchi S, Ishii R, Takeda M.

Department of Psychiatry and Behavioral Science, Osaka University Graduate
School of Medicine, Suita, Osaka 565-0871, Japan. ogawa@psy.med.osaka-u.ac.jjp

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a
possible treatment for psychiatric and neurological disorders characterized by
focal brain excitability, such as major depression and action myoclonus.
However, the mechanism of modulating excitability by rTMS is unclear. We
examined the changes in high frequency oscillations (HFOs) of somatosensory
evoked potentials (SEPs) before and after slow rTMS over the right primary
somatosensory cortex (0.5 Hz, 50 pulses, 80% motor threshold intensity). The
HFOs, which represent a localized activity of intracortical inhibitory
interneurons, were significantly increased after slow rTMS, while the SEPs were
not changed. Our results suggest that slow rTMS affects cortical excitability by
modulating the activity of the intracortical inhibitory interneurons beyond the
time of the stimulation and that rTMS may have therapeutic effects on such

PMID: 15039114 [PubMed – indexed for MEDLINE] Ned Tijdschr Geneeskd. 2004 Feb 28;148(9):410-5.

Comment in:
Ned Tijdschr Geneeskd. 2004 Feb 28;148(9):408-10.

[Repetitive transcranial magnetic stimulation in depression; stimulation of the
brain in order to cure the psyche] [Article in Dutch]

Helmich RC, Snijders AH, Verkes RJ, Bloem BR.

Universitair Medisch Centrum St Radboud, Postbus 9101, 6500 HB Nijmegen.

Transcranial magnetic stimulation (TMS) is a non-invasive approach to briefly
stimulate or inhibit cortical brain areas. A novel approach entails the delivery
of repetitive TMS pulses (rTMS) at a fixed frequency. In rTMS cortical activity
is altered beyond the period of actual stimulation. The changes occur locally as
well as at a distance in functionally connected brain areas. These features
render rTMS a suitable tool to study normal brain functions and the
pathophysiology of brain diseases. Furthermore, it is expected that rTMS could
be used as a novel therapy for neurological or psychiatric diseases
characterised by abnormal cortical activation. This possibility has been studied
mostly in patients suffering from depression, where rTMS has been used to
restore normal activity in the hypoactive prefrontal cortex. Despite
statistically significant therapeutic effects in small sized trials, the
clinical implications are still limited.

Publication Types:
Review, Tutorial

PMID: 15038199 [PubMed – indexed for MEDLINE] Ned Tijdschr Geneeskd. 2004 Feb 28;148(9):408-10.

Comment on:
Ned Tijdschr Geneeskd. 2004 Feb 28;148(9):410-5.

[Transcranial magnetic stimulation: a fascinating development] [Article in Dutch]

Koerselman GF.

Universitair Medisch Centrum Utrecht, afd. Psychiatrie, Heidelberglaan 100, 3584
GA Utrecht.

Transcranial magnetic stimulation is a novel technique for safely stimulating or
inhibiting cortical brain functions. Its possible role in neurology and
psychiatry is the subject of a broad field of research. At present, standard
clinical implementation is not yet warranted. On the other hand, the technique
as such is quite promising, especially because it can pave the way to a
‘bottom-up’ approach to mental disorder, starting from basic psychobiological
concepts and then gradually developing in the direction of more complex clinical

Publication Types:

PMID: 15038198 [PubMed – indexed for MEDLINE] Depress Anxiety. 2004;19(1):59-62.

Slow right prefrontal transcranial magnetic stimulation as a treatment for
medication-resistant depression: a double-blind, placebo-controlled study.

Kauffmann CD, Cheema MA, Miller BE.

Over the past decade, efforts have been made to assess the positive therapeutic
effects of transcranial magnetic stimulation (TMS) by altering the excitability
of the brain. We conducted a double-blind, placebo-controlled study to assess
the efficacy of right prefrontal slow repetitive TMS in patients with treatment
refractory major depression. This pilot study supports the therapeutic potential
of rTMS in the low-frequency range of 1 Hz on right prefrontal cortex for the
treatment of refractory major depression. Additional studies will be necessary
to assess the efficacy of rTMS with different indices (frequency, intensity, and
stimulation site) for major depression and other psychiatric diseases. Copyright
2004 Wiley-Liss, Inc.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 14978787 [PubMed – indexed for MEDLINE] Depress Anxiety. 2004;19(1):24-30.

Shorter duration of depressive episode may predict response to repetitive
transcranial magnetic stimulation.

Holtzheimer PE 3rd, Russo J, Claypoole KH, Roy-Byrne P, Avery DH.

Department of Psychiatry and Behavioral Sciences, University of Washington
Medical Center, Harborview Medical Center, Seattle, Washington 98104, USA.

We investigated repetitive transcranial magnetic stimulation (rTMS) as a
treatment for major depression. The experimental design comprised 15
medication-free subjects with major depressive disorder who were randomly
assigned to receive 10 sessions of active or sham 10-Hz rTMS to the left
dorsolateral prefrontal cortex at 110% motor threshold. Depression severity was
measured by the Hamilton Depression Rating Scale (HDRS) and Beck Depression
Inventory (BDI). Nonresponders to sham were allowed to receive active rTMS with
the same parameters. Response to treatment was analyzed using a random
regression model including episode duration and number of prior antidepressant
treatments as covariates. Treatment (rTMS vs. sham) did not significantly
predict changes in depression severity. Shorter duration of episode and more
lifetime treatment trials significantly predicted improvements in BDI but not
HDRS scores. Data from all subjects who received active rTMS (n = 14) showed
that those with a depressive episode duration of shorter than 4 years had a mean
HDRS decrease of 52% compared to 6% in those with an episode duration longer
than 10 years. Active rTMS was well tolerated and was not associated with
neuropsychological decrements when compared to sham. No significant
antidepressant effects were found for 2 weeks of rTMS compared to sham. Among
all subjects receiving rTMS those with a shorter duration of the current episode
showed a greater response. Patients may need more than 10 treatments to obtain
full benefit from rTMS. The design of future rTMS studies should consider these
issues. Copyright 2004 Wiley-Liss, Inc.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 14978782 [PubMed – indexed for MEDLINE] Biol Psychiatry. 2004 Feb 15;55(4):398-405.

Repetitive transcranial magnetic stimulation as treatment of poststroke
depression: a preliminary study.

Jorge RE, Robinson RG, Tateno A, Narushima K, Acion L, Moser D, Arndt S,
Chemerinski E.

Department of Psychiatry, Carver College of Medicine, University of Iowa,
Psychiatry Research/2-202 MEB, Iowa City, IA 52242-1000, USA.

BACKGROUND: Depression has a significant impact on poststroke recovery and
mortality. There are a proportion of patients with poststroke depression (PSD)
who do not respond to antidepressants. Repetitive Transcranial Magnetic
Stimulation (rTMS) might be a safe and effective alternative in these refractory
cases. METHODS: We conducted a randomized, parallel, double-blind study of
active versus sham left prefrontal rTMS in patients with refractory PSD. After
discontinuing antidepressants, patients were randomly assigned to receive 10
sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds
duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores,
response and remission rates. Patients completed a neuropsychological battery at
baseline and after completing the protocol. RESULTS: When compared with sham
stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal
cortex were associated with a significant reduction of depressive symptoms. This
reduction was not influenced by patient’s age, type or location of stroke,
volume of left frontal leukoaraiosis or by the distance of the stimulating coil
to the prefrontal cortex. However, there was a significant positive correlation
between the percentage of reduction of Ham-D scores and frontal gray and white
matter volumes. There were no significant changes in cognitive functioning
between the active and the sham stimulation groups. In addition, there were few
and mild adverse effects that were equally distributed among groups.
CONCLUSIONS: Taken together, these preliminary findings suggest that rTMS may be
an effective and safe treatment alternative for patients with refractory
depression and stroke.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 14960293 [PubMed – indexed for MEDLINE] J Neurol Neurosurg Psychiatry. 2004 Feb;75(2):320-2.

No benefit derived from repetitive transcranial magnetic stimulation in
depression: a prospective, single centre, randomised, double blind, sham
controlled “add on” trial.

Hausmann A, Kemmler G, Walpoth M, Mechtcheriakov S, Kramer-Reinstadler K,
Lechner T, Walch T, Deisenhammer EA, Kofler M, Rupp CI, Hinterhuber H, Conca A.

University Hospital Innsbruck, Department of General Psychiatry, Innsbruck,
Austria. armand.hausmann@uibk.ac.at

Repetitive transcranial magnetic stimulation (rTMS) has been reported to
demonstrate slight effects in the treatment of depression. Hence, a novel
bilateral versus unilateral and sham stimulation design was applied to further
assess rTMS’ antidepressant effects. Forty one medication free patients with
major depression, admitted to a psychiatric unit specialising in affective
disorders, were consecutively randomised into 3 groups. Group A1 (n = 12)
received unilateral active stimulation consisting of high frequency (hf) rTMS
over the left dorsolateral prefrontal cortex (LDLPC) and subsequent sham low
frequency (lf) rTMS over the right dorsolateral prefrontal cortex (RDLPC). Group
A2 (n = 13) received simultaneous bilateral active stimulation consisting of
hf-rTMS over the LDLPC and lf-rTMS over the RDLPC. Group C (n = 13) received
bilateral sham stimulation. Stimulation was performed on 10 consecutive
workdays. All patients received antidepressant medication on the first day of
stimulation, which was continued during and after the stimulation period. As no
significant difference in antidepressant outcome between group A1 and A2 was
found, the two groups were pooled. The time course of the outcome variables
Hamilton depression rating scale (HDRS(21)) and Beck depression inventory (days
0, 7, 14, 28) by repeated measures analysis of variance revealed no significant
group differences (in terms of a group by time interaction), whereas there was a
significant effect of time on all three outcome variables in all groups. The
results suggest that rTMS as an “add on” strategy, applied in a unilateral and a
bilateral stimulation paradigm, does not exert an additional antidepressant

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 14742619 [PubMed – indexed for MEDLINE] Int J Ment Health Nurs. 2003 Mar;12(1):22-9.

Information for assistants of repeated transcranial magnetic stimulation.

Pridmore S, Khan U, Rosa MA, George MS.

Department of Psychological Medicine, Royal Hobart Hospital, Discipline of
Psychiatry, University of Tasmania, GPO Box 1061 L, Hobart 7001, Tasmania,
Australia. s.pridmore@utas.edu.au

Repeated transcranial magnetic stimulation (rTMS) is an exciting new technology
being used in psychiatric and neurological research in many centres around the
world. rTMS has been accepted as a routine treatment of depression in Canada and
Israel. To this point, it has been exclusively conducted by medical officers. As
knowledge and experience grows, it is probable that professionals with other
backgrounds will have the opportunity to play a role. The aim of this paper is
to provide information that will be valuable to assistants. Electromagnetic
principles are harnessed to deliver electric currents to localized regions of
the cortex. rTMS does not involve anaesthesia or seizure. Side-effects appear to
be few. Much remains uncertain, however, even including the most appropriate
treatment parameters.

Publication Types:
Review, Tutorial

PMID: 14685956 [PubMed – indexed for MEDLINE] Int J Neuropsychopharmacol. 2003 Dec;6(4):371-8.

Motor-evoked potential amplitudes elicited by transcranial magnetic stimulation
do not differentiate between patients and normal controls.

Grunhaus L, Polak D, Amiaz R, Dannon PN.

Psychiatry Division, Sheba Medical Centre, Tel Hashomer, Israel.

Transcranial magnetic stimulation (TMS) applied over the motor cortex
depolarizes neurons and leads to motor-evoked potentials (MEP). To assess
cortico-spinal excitability we compared the motor threshold (MT) and the
averaged MEP amplitude generated by TMS in patients with major depression (MD)
and matched controls. Nineteen patients, who where participants in a protocol
comparing the antidepressant effects of rTMS with those of ECT, and thirteen
age- and gender-matched normal controls were studied. MT was similar between
patients and normal controls. The MEP amplitude response was significantly
increased by rTMS, however, the magnitude of the response was similar in
patients and normal controls. Correlations between the averaged MEP amplitude
and age revealed that older subjects demonstrated significantly lower responses
at all time-points. We conclude that cortico-spinal excitability is increased
following rTMS, however, differences between patients and normal controls were
not apparent with the paradigm used.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 14604452 [PubMed – indexed for MEDLINE] Arch Gen Psychiatry. 2003 Oct;60(10):1002-8.

Transcranial magnetic stimulation in the treatment of depression: a
double-blind, placebo-controlled trial.

Fitzgerald PB, Brown TL, Marston NA, Daskalakis ZJ, De Castella A, Kulkarni J.

Alfred Psychiatry Research Centre, The Alfred Hospital, and the Department of
Psychological Medicine, Monash University, Australia.

BACKGROUND: High-frequency left-sided repetitive transcranial magnetic
stimulation (HFL-TMS) has been shown to have antidepressant effects in
double-blind trials. Low-frequency stimulation to the right prefrontal cortex
(LFR-TMS) has also shown promise, although it has not been assessed in
treatment-resistant depression and its effects have not been compared with those
of HFL-TMS. OBJECTIVE: To prospectively evaluate the efficacy of HFL-TMS and
LFR-TMS in treatment-resistant depression and compared with a sham-treated
control group. DESIGN: A double-blind, randomized, sham-controlled trial.
SETTING: Two general psychiatric services. PARTICIPANTS: Sixty patients with
treatment-resistant depression who had failed to respond to therapy with
multiple antidepressant medications were divided into 3 groups of 20 that did
not differ in age, sex, or any clinical variables. All patients completed the
double-blind phase of the study. INTERVENTIONS: Twenty 5-second HFL-TMS trains
at 10 Hz and five 60-second LFR-TMS trains at 1 Hz were applied daily. Sham
stimulation was applied with the coil angled at 45 degrees from the scalp,
resting on the side of one wing of the coil.Main Outcome Measure Score on the
Montgomery-Asberg Depression Rating Scale. RESULTS: There was a significant
difference in response among the 3 groups (F56,2 = 6.2), with a significant
difference between the HFL-TMS and sham groups and between the LFR-TMS and sham
groups (P<.005 for all) but not between the 2 treatment groups. Baseline
psychomotor agitation predicted successful response to treatment. CONCLUSIONS:
Both HFL-TMS and LFR-TMS have treatment efficacy in patients with
medication-resistant major depression. Treatment for at least 4 weeks is
necessary for clinically meaningful benefits to be achieved. Treatment with
LFR-TMS may prove to be an appropriate initial repetitive TMS strategy in
depression taking into account safety, tolerability, and efficacy

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 14557145 [PubMed – indexed for MEDLINE] Psychiatry Res. 2003 Aug 30;120(1):95-101.

Reductions in phenomenological, physiological and attentional indices of
depressive mood after 2 Hz rTMS over the right parietal cortex in healthy human

van Honk J, Schutter DJ, Putman P, de Haan EH, d’Alfonso AA.

Helmholtz Research Institute, Utrecht University, Heidelberglaan 2, 3584 CS,
Utrecht, The Netherlands. J.vanHonk@fss.uu.nl

Research into emotion and emotional disorders by repetitive transcranial
magnetic stimulation (rTMS) has largely been restricted to the prefrontal
regions. There is, however, also evidence for the parietal cortex being
implicated in emotional (dys-)functioning. Here we used rTMS to investigate a
role of the right parietal cortex in depression. In a placebo-controlled design,
2 Hz rTMS at 90% of the individual motor threshold (MT) was applied over the
right parietal cortex of eight healthy subjects for 20 min continuously. Effects
on mood, autonomic activity and motivated attention were investigated.
Significant reductions in depressive mood were observed immediately following
and 30 min after stimulation. Moreover, these findings were objectified by a
concurring pattern of autonomically mediated changes in the attentional
processing of angry facial expressions. These data suggest a role for the right
parietal cortex in affective brain circuits regulating phenomenological,
physiological and attentional aspects of depressive functioning.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 14500118 [PubMed – indexed for MEDLINE] Fortschr Neurol Psychiatr. 2003 Sep;71(9):449-57.

[Interhemispheric transfer and its implications for neurology and psychiatry] [Article in German]

von Richthofen S, Tabrizian S, Grabe HJ, Meyer BU.

Klinik fur Psychiatrie und Psychotherapie des Universitatsklinikums Eppendorf,

The corpus callosum (CC) is the brain’s most important connection between
cortical areas of both hemispheres. Due to the hemispheric lateralisation of
brain function, information transfer between both hemispheres is vital for an
optimal performance in tasks, in which several psycho-motor functions have to be
integrated. Dysfunction of the CC can lead to deficits in neuropsychological
tasks and could contribute to pathologies underlying psychiatric illnesses. In
this review the normal and abnormal development of the CC as well as its macro-
and microscopic anatomy will be outlined. Then the detrimental effects of
operative callosomy on different modalities, e. g. on vision, the somatosensory
and the auditory system, will be discussed. Two electrophysiological methods
will be introduced, with which interhemispheric communication can be studied:
hemispheric transfer in rapid visuo-motoric tasks (CUD) and transcallosal
inhibition (TI), a phenomenon which occurs in a special paradigm of transcranial
magnetic stimulation. A first study found TI to be reduced in unmedicated
schizophrenic patients. This suggests that an inhibition between motor cortices
could be reduced in schizophrenic patients. Further results of other studies,
which have analysed the CC and interhemispheric transfer in schizophrenic
patients, will be introduced and discussed. In future experiments, the
contribution of dysfunctions of transcallosal transfer to psychopathological
symptoms and neuropsychological deficits in schizophrenia should be studied.

Publication Types:
Review, Tutorial

PMID: 12975730 [PubMed – indexed for MEDLINE] Int J Neuropsychopharmacol. 2003 Sep;6(3):233-41.

Modulation of frequency and duration of repetitive magnetic stimulation affects
catecholamine levels and tyrosine hydroxylase activity in human neuroblastoma
cells: implication for the antidepressant effect of rTMS.

Shaul U, Ben-Shachar D, Karry R, Klein E.

Laboratory of Psychobiology, Department of Psychiatry, Rambam Medical Center and
B. Rappaport Faculty of Medicine, Technion IIT, Haifa, Israel.

Transcranial magnetic stimulation (TMS), which is produced by strong non-static
magnetic fields, is a non-invasive means to stimulate the cerebral cortex.
Studies from recent years show that TMS affects mood in healthy subjects and
improves depressive symptoms in patients with major depression. However, the
relationship between the clinical efficacy of TMS and stimulation parameters is
still obscure. In the present study we have investigated the effects of
different stimulation frequencies and number of treatments on catecholamine
turnover in SH-SY5Y cell cultures. A single session of magnetic stimulation (1.7
T) caused a significant decrease in intracellular dopamine and L-DOPA and in
noradrenaline (NE) release at a rate of 3 Hz for 10 s but increased NE release
at a rate of 9 Hz. These alterations were associated with a reduction (47.8%) or
an increase (48%) in tyrosine hydroxylase (TH) activity after 3 and 9 Hz
magnetic stimulation, respectively. The latter may be related to the known
sensitivity of TH to neuronal firing rates and NE concentrations. Higher
stimulation frequencies (15, 20, 45 Hz) had no effect on catecholamine
metabolism. Unlike 3 Hz acute treatment, chronic treatment (3 Hz, 11 sessions,
for 4 d) had no effect on monoamines and TH activity was increased by 54.5% with
no change in its protein level. The results of the present study demonstrate
that in tissue culture system frequency and treatment duration of the magnetic
stimulation are important factors in affecting catecholamine turnover.
Considering the major role of catecholamine in the pathophysiology of
depression, these findings may be of relevance to the application of rTMS in
humans with major depression.

PMID: 12974989 [PubMed – indexed for MEDLINE] Psychol Med. 2003 Aug;33(6):997-1006.

High (15 Hz) and low (1 Hz) frequency transcranial magnetic stimulation have
different acute effects on regional cerebral blood flow in depressed patients.

Loo CK, Sachdev PS, Haindl W, Wen W, Mitchell PB, Croker VM, Malhi GS.

School of Psychiatry, University of New South Wales, Australia.

BACKGROUND: High and low frequency repetititve transcranial magnetic stimulation
(rTMS) are both effective in treating depression but have contrary effects on
motor cortical activity. This study aimed to understand further the mechanisms
of action of high and low frequency rTMS by examining their acute effects on
regional cerebral blood flow (rCBF) in depressed patients. METHOD: Eighteen
depressed subjects underwent brain single photon emission computerized
tomography (SPECT) scanning using split-dose 99mTc-HMPAO, and were examined
during sham and active rTMS to the left prefrontal cortex, at 15 Hz or 1 Hz (N=9
each). Relative rCBF changes were examined by statistical parametric mapping and
by regions of interest analysis. RESULTS: High (15 Hz) frequency rTMS resulted
in relative rCBF increases in the inferior frontal cortices, right dorsomedial
frontal cortex, posterior cingulate and parahippocampus. Decreases occurred in
the right orbital cortex and subcallosal gyrus, and left uncus. Low (1 Hz)
frequency rTMS led to increased relative rCBF in the right anterior cingulate,
bilateral parietal cortices and insula and left cerebellum. High frequency rTMS
led to an overall increase, whereas low frequency rTMS produced a slight
decrease, in the mean relative rCBF in the left dorsolateral prefrontal cortex.
CONCLUSIONS: High (15 Hz) and low (1 Hz) frequency rTMS led to different frontal
and remote relative rCBF changes, which suggests different neurophysiological
and possibly neuropsychiatric consequences of a change in frequency of rTMS.

Publication Types:
Clinical Trial

PMID: 12946084 [PubMed – indexed for MEDLINE]