Psychosurgery as a Treatment for Depression

Results of a MEDLINE Search by Ivan Goldberg, M.D.

1: Br J Neurosurg 2000 Oct;14(5):415-22; discussion 423

Depression: a role for neurosurgery?

Malhi GS, Bartlett JR.

Mood Disorders Unit, University Department of Psychiatry, Prince of Wales
Hospital, High Street, Randwick, Sydney, NSW 2031, Australia.

After providing an overview of depression this article briefly reviews the
development of psychosurgery and outlines the current procedures in use world
wide. Stereotactic subcaudate tractotomy (SST) is described in particular
detail, and the rationale for its use in the treatment of resistant depression
is then discussed by considering the findings of neuropsychological,
neurophysiological and neuroimaging studies. The emerging evidence suggests that
the prefrontal cortex subserves an essential function in emotion and that
disruption of its connections modifies mood.
2: Compr Psychiatry 1999 May-Jun;40(3):238-44

Chaos theories and therapeutic commonalities among depression, Parkinson’s
disease, and cardiac arrhythmias.

Toro MG, Ruiz JS, Talavera JA, Blanco C.

Complex Hospitalari, Mallorca, Islas Baleares, Spain.

This report reviews and compares all therapies that have shown efficacy in
depression and Parkinson’s disease, although some are not in current use and
others are at the experimental stage. They include pharmacological modification
of neurotransmitter pathways, electroconvulsive therapy (ECT), sleep
deprivation, psychosurgery, electrical stimulation through cerebral electrodes,
and transcranial magnetic stimulation. Stemming from a pathophysiological model
that stresses the brain as an open, complex, and nonlinear system, all therapies
have been attributed a common mechanism of action. This report suggests that the
therapeutic isomorphism is related to their ability to help the CNS deactivate
cortical-subcortical circuits that are dysfunctionally coupled. These circuits
are self-organized among neurons of their informational subsystem (rapid
conduction) and modulating subsystem (slow conduction). Finally, this report
extends the analysis and comparison of these therapies to some cardiac
3: J Neuropsychiatry Clin Neurosci 1999 Fall;11(4):436-43

Temporal lobe epilepsy, temporal lobectomy, and major depression.

Altshuler L, Rausch R, Delrahim S, Kay J, Crandall P.

UCLA Department of Psychiatry and Biobehavioral Sciences, Mood Disorders
Research Program 90095-7057, USA.

Sixty-two patients with medically intractable complex partial seizures who had
either surgical or no surgical intervention were followed up at a mean of 10.9
years after surgery or initial evaluation. Of the 49 surgical patients, 45% had
a life-time history of depression, versus 15% of the 13 patients in the
nonsurgical comparison group. In the surgical group, 77% had prior history of
depression; of these, 47% experienced no further episodes after surgery.
Depression occurred de novo after lobectomy in 5 surgical patients
(approximately 10%), 4 developing depression within 1 year. Presurgical presence
of depressive episodes predicted continued postoperative depressive episodes.
The significantly higher depression rate in patients with temporal lobe seizure
foci suggests limbic system dysfunction in the increased risk for depression.
Postsurgical resolution of episodes in almost 50% of these patients supports the
tenet that depression per se is not a contraindication for surgery in patients
with intractable seizures.
4: Psychiatr Clin North Am 1997 Dec;20(4):933-43

Neurosurgical treatment of neuropsychiatric illness.

Marino Junior R, Cosgrove GR.

Neurosurgical treatment of neuropsychiatric illness has evolved considerably
since its inception in 1935. The most common psychiatric indications for the
procedure, including obsessive-compulsive disorder and major depression, are
conceptualized as disorders involving the basal ganglia and limbic system. In
this article, the various operations and their contemporary applications are
discussed. Neurosurgical treatment represents a viable option in appropriate
candidates suffering from severe and otherwise treatment-refractory
neuropsychiatric diseases.
5: Stereotact Funct Neurosurg 1997;68(1-4 Pt 1):226-30

Differential approach to psychosurgery of obsessive disorders.

Korzenev AV, Shoustin VA, Anichkov AD, Polonskiy JZ, Nizkovolos VB, Oblyapin AV.

Bechterev Psychoneurological Research Institute, Russian Academy of Sciences,
Saint Petersburg, Russia.

One of the most frequent indications of psychosurgical treatment is incurable
obsessions. Up to now, capsulotomy or cingulotomy has been preferred. In our
opinion, the variety of obsessive conditions require a more thorough approach to
the selection of interbrain targets. Forty-seven patients with pure
obsessive-compulsive disorders as well as disorders connected with depressions,
epileptic syndrome, schizophreniform state and Gilles de la Tourette’s syndrome
with extremely severe resistance to medical therapy were examined. Eighteen
patients were operated on. Surgical treatment is permissible only in cases
fulfilling the three following criteria: (1) clinicopsychopathological
permissibility (duration of disease, resistance to medication,
psychopathological status); (2) physiological permissibility (the presence of a
brain target, defining the psychopathological status), and (3) technical
permissibility (the availability of proper stereotactic, imaging,
electrophysiological and other apparatus necessary to carry out the surgical
treatment). One supposes that the outcome of surgical treatment is determined by
all three criteria. For the purpose of improving the efficiency of stereotactic
treatment, a number of methods of surgical treatment depending on the
psychopathological status are suggested. For example, in case of comorbidity of
obsession with the epileptiform syndrome, we suggest cingulotomy (capsulotomy)
and amygdalotomy; in case of comorbidity with depression we suggest cingulotomy
and innominatotomy. The long-term observation of the outcome of stereotactic
treatment covers a period from 2 up to 9 years.
6: Br J Psychiatry 1994 Nov;165(5):599-611; discussion 612-3

Psychosurgery: stereotactic subcaudate tractomy. An indispensable treatment.

Bridges PK, Bartlett JR, Hale AS, Poynton AM, Malizia AL, Hodgkiss AD.

UMDS, Guy’s Hospital, London.

BACKGROUND. Stereotactic subcaudate tractotomy (SST) is the only type of
psychosurgery performed at the Geoffrey Knight Unit, London, where nearly 1300
operations have been done since 1961. Statistically reliable data are not
available to prove the effectiveness of SST. A detailed statement about
contemporary psychosurgery is given. METHOD. Relevant publications from the Unit
and via Medline are discussed. The outcome figures are reviewed. The outcome is
assessed at the Unit in global and clinical terms, associated with results of
self-completed questionnaires. RESULTS. SST allows 40-60% of patients to live
normal or near-normal lives, perhaps with continuation of medication. A
reduction in suicide rate to 1% post-operatively, from 15% in cases of
uncontrolled affective disorders is seen. CONCLUSION. As a treatment of last
resort, no controlled trial against a comparable treatment is possible. It
appears reasonable to offer SST to patients with suicidal and deluded depression
or with frequently swinging moods, not responding to other treatments.
7: Int Clin Psychopharmacol 1994 Jun;9 Suppl 2:5-10

Definition and differential diagnosis of treatment-resistant depression.

Burrows GD, Norman TR, Judd FK.

Department of Psychiatry, University of Melbourne, Austin Hospital, Heidelberg,
Victoria, Australia.

There are no agreed criteria for treatment-resistant depression, but the failure
to respond adequately to two successive courses of monotherapy with
pharmacologically different antidepressants, given in an adequate dose for
sufficient time is one pragmatic definition. Inherent within this definition are
notions of what constitutes an adequate dose of drug, the length of treatment
and pharmacological specificity of treatments. When these factors are accounted
for, treatment resistance may be encountered in 15-20% of patients. In
attempting to treat such patients a number of pharmacological strategies have
been adopted and some are briefly reviewed. Psychosurgery may have a role to
play in cases of absolute treatment resistance.
8: J Neuropsychiatry Clin Neurosci 1993 Summer;5(3):337-41

In vivo quantitation of basal ganglia and thalamic degenerative changes in two
temporal lobectomy patients with affective disorder.

Parashos IA, Oxley SL, Boyko OB, Krishnan KR.

Department of Psychiatry, Duke University Medical Center, Durham, North Carolina

The authors examined the brain magnetic resonance imaging scans of two epilepsy
patients who had temporal lobectomies, one on the right and one on the left,
with postoperative symptoms of affective disorders. Degenerative changes of
ipsilateral thalamus and putamen after surgery, with coincident affective
disorder, were noted. The authors discuss a possible relationship between
postlobectomy degeneration and depression.
9: Med J Aust 1992 Jul 6;157(1):17-9

Comment in:
Med J Aust. 1992 Sep 21;157(6):425-6

The present status of psychosurgery in Australia and New Zealand.

Hay PJ, Sachdev PS.

Department of Psychiatry, Warneford Hospital, Oxford, United Kingdom.

OBJECTIVES: To assess the extent and nature of psychosurgery currently being
performed in Australia and New Zealand, and the present status of legislation
regulating its practice. METHODS: Details of current legislation were obtained
through inspection of statutes and direct communication with Departments of
Health. All full and associate members of the Neurosurgical Society of
Australasia were surveyed by postal questionnaire. Ninety-eight neurosurgeons
were surveyed, of whom 72 (73%) replied. RESULTS: In the 1980s a mean of nine
(SD, 5.9) operations were performed per year; about two were performed per year
in the late 1980s. Ninety per cent of these operations were performed at one
centre in Sydney. The most common indications were severe and medically
intractable depression and obsessive-compulsive disorder. Surgery is now
exclusively stereotactic and involves the creation of lesions in the
orbitomedial frontal or cingulate tracts or a combination of the two. The nature
and type of surgery are comparable to those in other centres in the Western
world. Regulatory legislation is in place in most, but not all, States in
Australia and in New Zealand. CONCLUSIONS: Further developments of other forms
of psychiatric treatments may make psychosurgery, in its present form and at its
present level of validation, redundant. If it is to have a resurgence, it would
have to be based on a much sounder theoretical premise, and a stronger
demonstration of efficacy and predictability of effect.
10: Bratisl Lek Listy 1992 Jul;93(7):364-6

[Long-term results in patients with stereotaxic surgery for psychopathologic

[Article in Slovak]

Sramka M, Pogady P, Csokova Z, Pogady J.

Oddelenie stereotaktickej a funkcnej neurochirurgie Neurochirurgickej kliniky
LFUK, NsP L. Derera, Brastislava, CSFR.

Long-term results (5-20 years) recorded in 304 patients operated on
stereotactically for psychopathologic disorders are presented. The largest group
of 260 surgically treated subjects represented aggressive patients. This group
consisted of 150 patients with mental retardation, 70 with epilepsy, 20 with
schizophrenia, and 20 patients with sexual deviations. Amygdalectomy for
patients with normal intellect and posterior hypothalamotomy for those with
reduced intellect proved to be the most effective procedure. Symmetrical
operations were also effective. In some cases a combination of two target was
necessary. In epileptics with aggressivity the combination of amygdalectomy and
hippocampectomy yielded the best results. In aggressivity with sexual deviations
anterior hypothalamotomy was the most effective operation. Favorable results in
aggressivity therapy were recorded in 60% of patients. In patients with criminal
sexual deviations, in drug addicts, and in alcoholics, anterior hypothalamotomy
was found to be most effective, with favorable results in 50% of patients. In
patients with depression, thalamotomy or stimulation of the limbic regions of
the thalamus decreased the depression, with favorable results recorded in 66% of
patients. The results of the surgically treated patients show that
target-oriented stereotactic operations remove psychopathologic symptoms,
improve the effectiveness of psychoactive drugs and the social adaptability of
patients. (Ref. 15.)
11: Br J Psychiatry 1992 May;160:638-42

Effect of psychotropic drugs on excitatory amino acids in patients undergoing
psychosurgery for depression.

Pangalos MN, Malizia AL, Francis PT, Lowe SL, Bertolucci PH, Procter AW, Bridges
PK, Bartlett JR, Bowen DM.

Department of Neurochemistry, Institute of Neurology, London.

Samples of ventricular CSF were taken from 52 consecutive patients admitted for
psychosurgery for intractable depression. Concentrations of asparagine,
aspartate, glutamine, glutamic acid, and serine were determined. Glutamate and
aspartate concentrations, implicated in excitotoxic brain damage, were not
affected by various types of psychotropic drug treatment. Serine, a modulator of
glutamate responses, was significantly elevated in samples from subjects
receiving antidepressants. These subjects responded poorly to the operation.
Psychotropic drugs are unlikely to be neurotoxic. Nevertheless, antidepressants
may influence excitatory neurotransmission.
12: Int Clin Psychopharmacol 1991 Jul;6 Suppl 1:73-80; discussion 80-1

Psychosurgery for resistant depression: progress and problems.

Bridges P.

Guys Hospital and Medical School, London, UK.

Publication Types:
Review, tutorial
13: Br J Psychiatry 1991 Apr;158:523-8

Psychotic depression: psychoanalytic psychopathology in relation to treatment
and management.

Lund C.

Regional Department of Psychotherapy, Royal Victoria Infirmary, Newcastle upon

Jacobsen’s theory of affects and psychotic depression can be of benefit to the
management of patients, even when recourse to physical therapies is required.
Awareness of such psychodynamic issues would improve staff training, morale, and
practice; rotation schemes for junior staff may have serious effects through the
abandonment of patients and established therapeutic relationships.
14: Stereotact Funct Neurosurg 1991;57(4):175-94

Functional neurosurgery for psychiatric disorders: a historical perspective.

Diering SL, Bell WO.

Department of Neurosurgery, Bowman Gray School of Medicine, Wake Forest
University, Winston-Salem, N.C.

Functional neurosurgery for psychiatric disorders (‘psychosurgery’) has a
colorful, and sometimes dubious, history. From the time of the first operations
in 1935 to today, its usefulness has been overshadowed by doubts and ethical
questions. Psychosurgery became popular in the 1940s and early 1950s, especially
in the United States. Its main indications were for intractable mental illness,
in particular, depression, anxiety, and obsessive-compulsive disorders. However,
its side effects, especially the ‘frontal lobe syndrome’, led to the need for
more refined surgical approaches; the most important of these was the use of
stereotaxis. Cingulotomy, subcaudate tractotomy, limbic leucotomy, and anterior
capsulotomy are generally the stereotactic treatments of choice today.
Indications and postoperative sequelae vary slightly across treatments. The
indications remain as affective, anxiety, and obsessive-compulsive disorders.
Despite approval by the United States Department of Health, Education, and
Welfare in 1978, psychosurgery is still not a common treatment. This low
acceptance is perhaps due to continued concern over ethical problems and
inadequate reporting of outcomes.
15: Br J Psychiatry 1988 Mar;152:354-8

Resistant bipolar affective disorder treated by stereotactic subcaudate

Poynton A, Bridges PK, Bartlett JR.

United Medical School, Guy’s Hospital, London.

The results of stereotactic subcaudate tractotomy in nine patients with
resistant bipolar affective disorder are presented in the form of a single case
study with a summary of the other eight cases. Follow-up studies at 2-4 years
showed substantial improvement in five patients and amelioration of symptoms in
a further four patients, with a tendency for a greater improvement in the manic
than in the depressive episodes. These preliminary results suggest that there is
a place for this operation in the management of severe bipolar affective
disorders which are not responding to any other treatment, although decisive
recovery occurs less often than with unipolar depression.
16: Acta Neurochir Suppl (Wien) 1988;44:173-8

Ethics of psychosurgery.

Bouckoms AJ.

Harvard Medical School, Massachusetts General Hospital, Boston.

The ethics of psychosurgery involve questions of moral philosophy and pragmatism
in alleviating human suffering. The weighing of scientific data along with
philosophical oughts and shoulds is required. The medical literature indicates
definite efficacy for some kinds of limbic surgery, mainly cingulotomy and
capsulotomy, in some kinds of conditions, namely major depression, pain and
anxiety. The relative utility of these procedures given the severity of the
illnesses and the safety of the procedures described is significant. Ethical and
moral conflicts over altruism, autonomy and suffering require recognition before
their due considerations (Kleinig 1985). The following recommendations emerge
from these considerations: 1. No consideration of ethics in psychosurgery is
complete without consideration of both the scientific data and moral conflicts.
2. The considerable efficacy and safety of cingulotomy and capsulotomy must be
acknowledged. 3. Indications and contraindications do exist for selecting
patients. Major psychiatric Axis I diagnoses of depression and anxiety are the
indications. Personality disorders are not indications. 4. Peer review,
unfettered consent and knowledge of the psychodynamics of severe illness are
three ingredients necessary for wise decisions about performing limbic surgery.
5. The liberal advocation of autonomy without responsibility is an amoral, not
liberating, point of view. 6. Politics should be denounced as the most serious
ethical problem in medical decision making. Political intrusion into the
scientific matters and the doctor-patient relationship has created ethical
problems with psychosurgery and continues to do so today.
17: Acta Neurochir Suppl (Wien) 1988;44:167-9

Experiences in psycho-surgery in The Netherlands.

van Manen J, van Veelen CW.

Department of Neurology, Amsterdam Zuidoost, The Netherlands.

The authors report on their experiences in 54 cases operated upon for various
psychiatric diseases including compulsive neurosis, depression, anxiety, tension
and in some of this group also automutilation; intractable temporal lobe
epilepsy and aggressive behaviour; aggressive behaviour and minor epileptic
problems; severe mental retardation, restlessness, automultilation and in some
of this group also aggression. Operative procedures have been fronto-basal
lesions according to Knight and Bridges, as well as lesions in the cingulum, the
paracingular white matter, the anterior part of the radiation of the corpus
callosum and the basal frontal region, using the technique of Crow. Amygdalotomy
and thalamotomy was performed for epilepsy, aggression and automutilation in the
mentally retarded patients. Because of the small number of patients and the
variety of different diseases and techniques no statistically valid analysis of
the results is possible.
18: Acta Psychiatr Belg 1986 Mar-Apr;86(2):141-51

The management of resistant depression.

Levine S.

Between 10 and 30% of depressed patients, mostly bipolar, develop a
therapy-resistant illness. The known causes of such chronic evolutions are
discussed: misdiagnosis (underlying schizophrenia, personality disorder or
dementia), drug-induced depression (neuroleptics), systemic disease
(hypothyroidism, multiple sclerosis, cardiovascular or neoplastic disease etc.),
or lack of efficacy (drug compliance, insufficient dosage). Remedies are
suggested: adequate dosage, drug combination (Newcastle cocktail. tricyclic
antidepressant + MAOI, imipramine + T3), carbamazepine in lithium-resistant
cases, alprazolam, reduction in vanadium intake, sleep deprivation,
19: Acta Psychiatr Scand 1985 Aug;72(2):166-71

Ventricular size, the dexamethasone suppression test and outcome of severe
endogenous depression following psychosurgery.

Standish-Barry HM, Hale AS, Honig A, Bouras N, Bridges PK, Bartlett JR.

To assess the possible significance of cerebral ventricular size and the
dexamethasone suppression test (DST) in the outcome of severe endogenous
depression, 28 patients were followed up and reviewed 1 year after stereotactic
subcaudate tractotomy. Neither ventricular size nor the dexamethasone
suppression test predicted either a good or poor outcome. There was no
relationship between ventricular size and the DST results.
20: Acta Psychiatr Scand 1977 Jul;56(1):1-14

Studies of endocrine activity, plasma tryptophan and catecholamine excretion on
psychosurgical patients.

Sepping P, Wood W, Bellamy C, Bridges PK, O’Gormann P, Bartlett JR, Patel VK.

The Geoffrey Knight Psychosurgical Unit admits patients on a regular basis and
thus offers special opportunities for studying severely ill psychiatric cases,
all having one particular treatment under relatively controlled conditions. The
opportunity has been taken to repeat various metabolic studies previously
reported to be abnormal in some psychiatric illnesses. In the present
investigation several measures of endocrinological activity were studied, as was
plasma tryptophan, both free and bound. None of these data confirmed reports of
abnormalities and neither did the values found at operation help to predict
clinical outcome 1 year later, which was another possibility. Urinary
catecholamines were also measured and 2 weeks after operation. Male patients,
regardless of diagnosis, showed a mean increase in adrenaline output after
operation compared with the pre-operative value and this was significantly
different from the females, who showed a small mean decrease. The depressed
patients showed a significant reduction in noradrenaline excretion after
operation compared with before operation and this trend was enhanced in those of
good outcome at 1 year, the difference from those who responded poorly being
significant. It could be that the ventromedial lesion that is produced alters
noradrenaline metabolism or autonomic activity in depression and this
possibility merits further study.