The Treatment of Dysthymia

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

1: Phytomedicine. 2006 Jan 16; [Epub ahead of print]

The efficacy of St. John’s Wort in patients with minor depressive symptoms or
dysthymia – a double-blind placebo-controlled study.

Randlov C, Mehlsen J, Thomsen CF, Hedman C, von Fircks H, Winther K.

Department of Psychiatry, H:S Amager Hospital, Denmark.

Introduction: We studied the efficacy of St. John’s Wort compared with placebo
in patients with minor depressive symptoms or dysthymia, with the main focus on
which diagnostic entities are optimally amenable to treatment with two different
doses of Hypericum, and which are not. Methods: One hundred and fifty patients,
25-70 years old, meeting ICD-10 criteria for mild or moderately severe depressed
episodes or with dysthymia, and having a 17-item Hamilton Depression Scale for
Depression (HAM-D) total score between 7 and 17, were randomly assigned to an
extract. The extract, PM235, manufactured by Cederroth International AB, Sweden,
was given t.i.d. in a lower (0.12% hypericine) or a higher (0.18% hypericine)
formulation, based on 270mg extractions or identical placebo. Clinical response
was defined by HAM-D as a 50% reduction and/or a score 7. The Beck Depression
Inventory (BDI) and Visual Analog Scales (VAS) were used as secondary efficacy
parameters. Measures were conducted at screening, baseline, and after 3 and 6
weeks of treatment. Results: We found a large discrepancy in response between
dysthymic and non-dysthymics, the latter seemingly more sensitive to Hypericum.
HAM-D showed tendency but no significance toward a more frequent improvement of
the non-dysthymics treated with Hypericum (p=0.057). BDI criteria showed
significance (p=0.045) for both doses of Hypericum compared to placebo. Pooling
high- and low-dose groups together, a significant reduction for HAM-D7 and BDI
criteria was found among non-dysthymic patients (p=0.03). Significant
improvement in response to Hypericum was found in symptoms reflected by VAS –
again only in non-dysthymic patients (p=0.041). Discussion: We observed, a
tendency toward a more frequent significant improvement of the non-dysthymic
patient treated with PM235, though this did not reach the level of statistical
significance. In a secondary analysis, pooling both hypericine-treated groups
concluded that Hypericum has a clinical significant effect in minor depressed
patients with HAM-D up to 17. This finding was significant only in non-dysthymic
patients.

PMID: 16423519 [PubMed – as supplied by publisher]

2: Eur Neuropsychopharmacol. 2005 Nov 25; [Epub ahead of print]

A double-blind, randomised, controlled clinical trial of acetyl-l-carnitine vs.
amisulpride in the treatment of dysthymia.

Zanardi R, Smeraldi E.

Department of Psychiatry, School of Medicine, Vita-Salute University San
Raffaele, Milan, Italy.

Aim Evaluation of the effect of acetyl-l-carnitine (ALCAR) vs. amisulpride
measured by total Hamilton Depression Rating Scale score (HAM-D(21)) in patients
with pure dysthymia (DSM IV). Two hundred and four patients were randomised and
treated with ALCAR 500 mg b.i.d. or amisulpride 50 mg u.i.d. in a double-blind
study, for 12 weeks. Results A solid improvement of HAM-D(21) was observed in
both treatment groups throughout the study. The results did not disclose
statistically significant differences between treatments, although the
confidence interval for the non-inferiority of the primary end-point exceeded
the pre-established limit of 2 by 0.46 points. According to a non-inferiority
margin of 3 (considered acceptable by recent published data) the primary
end-point could have been fully satisfied. CDRS, MADRS and CGI, employed to
further measure the clinical outcome, reported similar results in both treatment
groups. The greater tolerability of ALCAR is of clinical relevance considering
the chronicity of dysthymia, which often requires prolonged treatment.

PMID: 16316746 [PubMed – as supplied by publisher]

3: Int Rev Psychiatry. 2005 Feb;17(1):3-8.

Dysthymia and double depression.

Dunner DL.

Department of Psychiatry & Behavioral Sciences, University of Washington Medical
School, Washington 98105, USA. ddunner@u.washington.edu

Dysthymic disorder is a chronic form of depression which is frequently
complicated by major depressive episodes. This paper renews the diagnostic
status of dysthymic disorder, treatment studies, and makes suggestions for the
classification of chronic forms of depression for DSM-V.

PMID: 16194766 [PubMed – indexed for MEDLINE]

4: J Affect Disord. 2004 Sep;81(3):191-9.

Dysthymia in later life: a study in the community.

Beekman AT, Deeg DJ, Smit JH, Comijs HC, Braam AW, de Beurs E, van Tilburg W.

Department of Psychiatry, Vrije Universiteit, Valerius Clinic, Valeriusplein 9,
1075 BG, Amsterdam, Netherlands. aartjanb@ggzba.nl

BACKGROUND: Dysthymia (DD) may be thought of as depression associated with
personality disorder, a phase in the pleomorphic natural history of unipolar
depression or a result of exposure to chronic physical illness. Prevalence,
clinical features, risk factors and prognosis may change with AGE. METHOD: Large
(n=3056) representative sample of elderly (55-85) in the Netherlands. Two-stage
screen procedure to identify elderly with DD. The Center for Epidemiologic
Studies Depression scale (CES-D) was used as a screen and the Diagnostic
Interview Schedule (DIS) to diagnose DD. Data on 277 depressed elderly were
available to assess the 6-year prognosis of DD. RESULTS: The prevalence of DD
(4.61%) was higher in women and declined with age. The symptom profiles of DD
and MDD were very similar. Those with DD were very likely to have had MDD
earlier in life (44% in pure DD and 80% in those with double depression). The
average age at onset (31 years) was earlier than in MDD (53 years).
Environmental and personal vulnerability dominated the risk-factors. The
prognosis was unfavourable in most cases. LIMITATIONS: Considerable attrition
and retrospective data on age at onset and previous histories of depression.
CONCLUSION: Although the prevalence declines with age, DD remains common in
later life. Many cases arise later than is often thought and clinical features
intertwine with those of MDD in the course of life. Given the unfavourable
prognosis, provision of effective treatment is warranted.

PMID: 15337323 [PubMed – indexed for MEDLINE]

5: J Psychopharmacol. 2004 Sep;18(3):417-22.

Effects of reboxetine on sleep and nocturnal cardiac autonomic activity in
patients with dysthymia.

Ferini-Strambi L, Manconi M, Castronovo V, Riva L, Bianchi A.

Sleep Disorders Center, Universita Vita-Salute, IRCCS H San Raffaele, Italy.
ferinistrambi.luigi@hsr.it

Antidepressants may have sleep and autonomic side-effects. The acute and
long-term effect of reboxetine (2 mg b.i.d.) on sleep and cardiac autonomic
activity was compared with that of placebo in a single-blind study. Twelve
patients affected by dysthymia underwent four polysomnographic studies at
baseline (placebo); at night 3 (reboxetine; acute effect); at night 9
(reboxetine; intermediate-term effect); and at night 122 (reboxetine; chronic
effect). After the first administration, reboxetine increased time awake after
sleep onset, number of awakenings, percentage of stages 1 and 2 non-rapid eye
movement (REM), and reduced the amount of stages 3-4 non-REM, but all these
effects disappeared by continuing treatment. However, reboxetine caused a
persistent suppression of REM sleep, which was accompanied by an increase of REM
sleep latency. The spectral analysis of heart rate variability showed a trend
towards an increase in sympathetic activity with both acute and intermediate
reboxetine use. Long-term treatment with 4 mg reboxetine does not cause
significant changes in cardiac autonomic function.

Publication Types:
Clinical Trial

PMID: 15358987 [PubMed – indexed for MEDLINE]

6: Psychol Psychother. 2004 Sep;77(Pt 3):335-51.

Becoming a self-therapist: using cognitive-behavioural therapy for recurrent
depression and/or dysthymia after completing therapy.

Glasman D, Finlay WM, Brock D.

University of Surrey, Guildford, Surrey GU2 7XH, UK.

OBJECTIVES: To explore the ways in which people use cognitive-behavioural
therapy (CBT) for recurrent depression and/or dysthymia after leaving therapy.
DESIGN: A qualitative interview was used in this study. METHOD: Semi-structured
interviews were carried out with nine people who had completed a course of CBT
at least three months previously. The interviews explored their use of CBT
techniques or models outside of therapy and their everyday management of
depression. RESULTS: Eight of the nine participants reported engaging in some
self-therapeutic activity, and identified depression, or the threat of
depression, as a continuing presence in their lives. They used a range of
techniques, either directly transferred from therapy or modified in some way,
and identified a number of changes in the way they reacted to difficult
situations or negative emotions. These included enactive responses such as
leaving the room, making self-efficacy statements, or remembering what the
therapist had said to them. Participants also described situations in which they
could not use the things they had learnt in CBT. Finally, a range of factors
that influenced the ways in which participants became self-therapists were
identified. CONCLUSIONS: A number of implications for clinical practice are
described. An understanding of how people modify CBT and use it (or not) in
their everyday lives is important to understanding and improving effectiveness.

Publication Types:
Clinical Trial

PMID: 15355585 [PubMed – indexed for MEDLINE]

7: CNS Drugs. 2003;17(13):927-46.

Diagnosis and treatment of dysthymia in children and adolescents.

Nobile M, Cataldo GM, Marino C, Molteni M.

Child Psychiatry Unit, Scientific Institute, Bosisio Parini (LC), Italy.
mnobile@bp.lnf.it

Dysthymic disorder is a chronic depressive condition occurring in 0.6-4.6% of
children and 1.6-8.0% of adolescents. Although symptoms are less severe than
those observed in major depression, childhood-onset dysthymic disorder is
characterised by a persistent and long-term depressed or irritable mood (mean
episode duration 3-4 years), a worse outcome than major depression and,
frequently, comorbid disorders (in around 50% of patients). Long-lasting
depressive symptoms seem responsible for long-term disabling consequences on
social skill learning, psychosocial functioning and consequent professional
life, probably contributing to a higher risk of relapse or development of major
depression. Consistently, the first episode of major depression occurs 2-3 years
after the onset of dysthymic disorder, suggesting that the latter is one of the
gateways to recurrent mood disorders. The primary aims of treatment for
dysthymic disorder should be to resolve depressive symptoms, reduce the risk of
developing other mood disorders over time and strengthen psychosocial
functioning, especially in children and adolescents, in order to prevent the
potentially serious sequelae of this disorder. As children with dysthymia often
have multiple problems, interventions should involve multiple levels and
measures: individual psychotherapy, family therapy/education and pharmacological
treatment. Psychotherapeutic techniques, such as cognitive-behaviour therapy and
interpersonal therapy, have been found to be efficacious interventions in
treating children and adolescents with mild to moderate depression in studies
including patients with either dysthmia or double depression. SSRIs are the
first-line drug treatment for children and adolescents because of their safety,
adverse effect profile and ease of use (the safety of paroxetine is currently
under investigation). Several nonblind studies have shown the efficacy and good
tolerability of SSRIs in children and adolescents with dysthymic disorder, but
further research is needed to confirm their efficacy and that of newer
antidepressants in the treatment of this disorder. Regardless of whether
psychotherapeutic or medical treatments are planned, according to clinical
experience, psychoeducational interventions and psychosocial support should be
provided to parents and other caregivers during the acute treatment phase to
help manage the child’s irritable mood and foster a therapeutic alliance and
better compliance with treatment. Unfortunately, no studies have focused on
continuation treatment of paediatric dysthymic disorder. Given the chronicity,
recurrence, psychosocial consequences and peculiar response pattern to treatment
of dysthymic disorder, establishing effective ‘acute’ and ‘continuation’
interventions in this group of patients should be a priority in mental health
management.

Publication Types:
Review

PMID: 14533944 [PubMed – indexed for MEDLINE]

8: Cochrane Database Syst Rev. 2003;(3):CD004047.

A comparison of active drugs for the treatment of dysthymia.

Silva de Lima M, Hotopf M.

Department of Mental Health, Universidade Federal de Pelotas, Avenida Duque de
Caxias, 250, Pelotas 96100, Rio Grande do Sul, Brazil. mslima@nutecnet.com.br

BACKGROUND: Many drug treatments have been proposed for the treatment of
dysthymia, but with so many potential comparisons it is not possible at the
present time to determine which is the treatment of choice. There is a need to
know whether the different classes of antidepressants have similar efficacy. In
addition, the tolerability of treatments may be even more important, since
dysthymia is a chronic condition characterised by less severe symptoms than
major depression. OBJECTIVES: To conduct a systematic review of all randomised
controlled trials comparing two or more active drug treatments for dysthymia.
SEARCH STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE,
PsycLIT and LILACS, Biological Abstracts; reference searching; personal
communication; unpublished trials from pharmaceutical industry. SELECTION
CRITERIA: Only randomised and quasi-randomised controlled trials were included.
Trials had to compare at least two active drug treatments in the treatment of
dysthymia. Exclusion criteria were: non-randomised studies, studies which
included patients with mixed major depression/dysthymia and studies on
depression/dysthymia secondary to other disorders (e.g. substance abuse). DATA
COLLECTION AND ANALYSIS: The reviewers extracted the data independently and odds
ratios, weighted mean difference and number needed to treat were estimated. The
reviewers assumed that people who died or dropped out had no improvement and
tested the sensitivity of the final results to this assumption. MAIN RESULTS: A
total of 14 trials were eligible for inclusion in the review. All studied drugs
promoted similar clinical responses, although with different side effect
profiles. The evidence for TCAs and SSRIs was the most robust, considering the
number of trials and participants. REVIEWER’S CONCLUSIONS: The conclusion is
that the choice of drug must be made based on consideration of drug-specific
side effect properties.

Publication Types:
Meta-Analysis
Review

PMID: 12918001 [PubMed – indexed for MEDLINE]

9: Drug Saf. 2003;26(1):55-64.

Benefits and risks of pharmacotherapy for dysthymia: a systematic appraisal of
the evidence.

De Lima MS, Hotopf M.

Universidade Federal de Pelotas, Rio Grande do Sul, Brazil. mslima@terra.com.br

BACKGROUND: Dysthymia is a prevalent form of subthreshold depressive disorder,
associated with considerable disability and high co-morbidity. This paper
systematically appraises the evidence for the efficacy and acceptability of the
pharmacological treatment for this condition. METHODS: Randomised, controlled
trials evaluating the efficacy of drug therapies for dysthymia were included. A
comprehensive search of the literature was performed, aiming to avoid
publication bias. Pooled relative risks (RR) and 95% CIs were calculated with
the Random Effect Model method. The number needed to treat (NNT) and number
needed to harm (NNH) were estimated for statistically significant results.
RESULTS: Twenty-five trials were included for the main comparisons. Regarding
placebo-controlled trials (n = 16), similar results were obtained in terms of
efficacy for different groups of drugs, such as tricyclic antidepressants
(TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase
inhibitors (MAOIs) and other drugs (sulpiride, amineptine, and ritanserin). The
pooled RR for treatment response was 0.68 (95% CI 0.57-0.81) for TCA and the NNT
was 4.3 (95% CI 3.2-6.5); 0.68 (95% CI 0.56-0.82) for SSRIs (NNT 5.1; 95% CI
3.9-7.7); 0.59 (95% CI 0.48-0.71) for MAOIs (NNT 2.9; 95% CI 2.2-4.3). Other
drugs (amisulpride, amineptine and ritanserin) showed similar results. The
equivalent efficacy between antidepressants as found in trials where active
medications were compared confirmed the efficacy findings from placebo trials.
In general, patients treated with a TCA were more likely to report adverse
events, compared with placebo and SSRIs. CONCLUSIONS: Pharmacotherapy for
dysthymia appears to be an effective short-term treatment for dysthymic
disorder. Newer antidepressants are equally effective and have better
acceptability than TCAs, although their higher cost must be balanced against
this assumed advantage.

Publication Types:
Review

PMID: 12495364 [PubMed – indexed for MEDLINE]

10: J Am Board Fam Pract. 2003 Jan-Feb;16(1):22-31.

Patient beliefs predict response to paroxetine among primary care patients with
dysthymia and minor depression.

Sullivan MD, Katon WJ, Russo JE, Frank E, Barrett JE, Oxman TE, Williams JW Jr.

Department of Psychiatry, University of Washington, Seattle 98195, USA.

BACKGROUND: Dysthymia and minor depression are common problems in primary care,
but it is not known how patient health beliefs shape response to antidepressant
treatment of these less severe forms of depression. METHODS: Three hundred
thirty-three primary care patients with dysthymia or minor depression received
at least 4 weeks of paroxetine or placebo in a multicenter, randomized
controlled 11-week trial. Patient health beliefs and other characteristics were
examined as predictors of treatment adherence and depression remission. RESULTS:
Patient beliefs were not predictive of adherence to paroxetine or placebo.
Patients with less endorsement of biological beliefs about their condition (odds
ratio [OR] = 3.40), higher perceived general health (OR = 3.38), meeting
criteria for dysthymia (OR = 2.37), and age younger than 60 years (OR = 2.68)
were more likely to achieve remission on paroxetine. Patient beliefs did not
predict remission on placebo. Those with lower severity of depression symptoms
at baseline (OR = 2.70) and women (OR = 2.18) were most likely to achieve
remission on placebo. CONCLUSIONS: Our results suggest that patients with
dysthymia or minor depression are more likely to respond to antidepressant
medication if they do not see their depression as a biological illness and see
themselves as generally healthy. It is clearly not necessary for patients to
believe that their dysthymia or minor depression is biological to respond to
antidepressant medication.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 12583647 [PubMed – indexed for MEDLINE]

11: J Abnorm Psychol. 2002 May;111(2):350-6.

Response styles among patients with minor depression and dysthymia in primary
care.

Schmaling KB, Dimidjian S, Katon W, Sullivan M.

College of Health Sciences, University of Texas at El Paso, 79902, USA.
schmaling@utep.edu

Ruminative responses to depression have predicted duration and severity of
depressive symptoms. The authors examined how response styles change over the
course of treatment for depression and as a function of type of treatment. They
also examined the ability of response styles to predict treatment outcome and
status at follow-up. Primary care patients (n = 96) with dysthymia or minor
depression were randomly assigned to problem-solving therapy, paroxetine, or
placebo. Patients’ depressive symptoms and rumination, but not distraction,
decreased over time. Pretreatment rumination and distraction were associated
with more depressive symptoms at the conclusion of treatment; the latter finding
was not consistent with the response style theory of depression. Results are
discussed in terms of their implications for this theory.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 12003456 [PubMed – indexed for MEDLINE]

12: Gen Hosp Psychiatry. 2002 Jan-Feb;24(1):20-7.

Predictors of nonresponse to treatment in primary care patients with dysthymia.

Katon W, Russo J, Frank E, Barrett J, Williams JW Jr, Oxman T, Sullivan M,
Cornell J.

Department of Psychiatry and Behavioral Sciences, University of Washington
Medical School, Seattle, WA, USA. wkaton@u.washington.edu

Dysthymia is one of the most prevalent problems in primary care, especially in
the elderly. In this study, we evaluated the demographic and clinical predictors
of nonresponse to treatment in primary care patients with dysthymia. The study
sample consisted of 338 primary care patients meeting DSMIII-R criteria for
dysthymia from 4 diverse geographic sites in a randomized controlled 11-week
trial of paroxetine, problem-solving therapy or placebo. Patients who attended
at least 4 treatment sessions were used in the analysis. A score of less than 7
on the Hamilton was defined as a positive response to treatment. By Week 11,
52.2% of patients had a positive response to treatment. Patients with lower
levels of education (odds ratio 0.44, 95% CI 0.23, 0.86), higher scores on the
personality dimension of neuroticism (odds ratio 0.58, 95% CI 0.36, 0.92) and
those with more severe medical illness (odds ratio 0.97, 95% CI 0.95, 0.99) were
less likely to recover with either active or placebo treatments. Elderly women
(>60 years of age; odds ratio 0.19, 95% CI 0.05, 0.66) were also less likely to
respond to all treatments; however, females had a significantly higher response
to placebo treatment compared to males. The factors associated with lack of
response to treatment included lower-levels of education, high neuroticism, more
severe medical illness and being an older female. This analysis is based on
patients agreeing to participate in a randomized controlled trial, limiting
representativeness of the sample, however, the demographic and clinical
characteristics are common in elderly depressed primary care patients, and may
signal the need for increased mental health specialty consultation.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11814530 [PubMed – indexed for MEDLINE]

13: Mol Psychiatry. 2002;7(3):247-53.

The substituted benzamides and their clinical potential on dysthymia and on the
negative symptoms of schizophrenia.

Pani L, Gessa GL.

Center for Neuropharmacology, National Research Council, Neuroscienze Scarl, via
Porcell 4, 09124-I Cagliari, Italy. panil@unica.it

In this paper the historical and scientific background that led to the use of
substituted benzamides in two apparently unrelated clinical conditions namely
dysthymic disorder and schizophrenia will be reviewed, in order to understand if
a common mechanism of action may support this dual therapeutic indication. The
dopaminergic antidepressant action of substituted benzamides such as sulpiride,
has been proposed, since the late 1970s, by several authors and extensively
explored in preclinical experiments by our group. In Italy the first marketing
authorization obtained for the new substituted benzamide amisulpride, was with
the sole indication of dysthymia and therefore a solid clinical experience
exists in the use of substituted benzamides in mild forms of depression, with
more than 1 000 000 patients being treated in the last 7 years. The proposed
mechanism of action of substituted benzamides implies a selective modulation of
the dopaminergic system in the mesocorticolimbic area, important for cognitive

processing of internal and external cues, related to survival. The selective
antagonism of dopamine D2-D3 receptors has been evoked to explain, in small to
moderate doses (ie 50-100 mg day(-1)), the antidepressant effect and, in
moderate to medium doses (100-400 mg day(-1)), the reported efficacy on negative
symptoms of schizophrenia. Thus, substituted benzamides could represent the
first class of atypical antipsychotics successfully employed for both depressive
states and schizophrenia. Interestingly, recent evidence in the literature
suggests that depressive episodes belonging to the bipolar spectrum are among
“alternative indications” of other atypical antipsychotics such as olanzapine
and risperidone.

Publication Types:
Review

PMID: 11920152 [PubMed – indexed for MEDLINE]

14: Gen Hosp Psychiatry. 2001 Nov-Dec;23(6):301-10.

Status of minor depression or dysthymia in primary care following a randomized
controlled treatment.

Oxman TE, Barrett JE, Sengupta A, Katon W, Williams JW Jr, Frank E, Hegel M.

Departments of Psychiatry and Community & Family Medicine, Dartmouth Medical
School, Lebanon, NH 03756, USA. thomas.oxman@dartmouth.edu

This report describes the rates of recovery and remission from minor depression
or dysthymia in primary care patients three months after completing a randomized
controlled treatment trial. The subjects were primary care patients who received
> or =4 treatment sessions with Problem-Solving Treatment, paroxetine, or
placebo and who completed an independent assessment 3 months after the study
(201 with minor depression, 229 with dysthymia). The 17-item Hamilton Rating
Scale for Depression (HAMD), semistructured questions about postintervention
depression treatments, and baseline medical comorbidity, neuroticism, and social
function were the primary measures. For minor depression 76% and for dysthymia
68% of subjects who were in remission at the end of the 11-week treatment trial
were recovered (HAMD < or =6) three months after the treatment trial. Of
patients who were not in remission at 11 weeks, for minor depression 37% and for
dysthymia 31% went on to achieve remission at 25 weeks. The majority of patients
chose not to use antidepressants or psychotherapy after the trial. Patients with
minor depression that had greater baseline social function and lower neuroticism
scores were more likely to be recovered. For patients with minor depression,
these findings suggest a need for some matching of continuation and maintenance
treatment to patient characteristics rather than uniform, automatic treatment
recommendations. Because of the chronic, relapsing nature of dysthymia,
practical improvements in encouraging effective continuation and maintenance
phases of treatment are indicated.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11738460 [PubMed – indexed for MEDLINE]

15: Int Clin Psychopharmacol. 2001 Nov;16(6):317-24.

Faster response on amisulpride 50 mg versus sertraline 50-100 mg in patients
with dysthymia or double depression: a randomized, double-blind, parallel group
study.

Amore M, Jori MC; AMISERT Investigators.

Institute of Psychiatry, University of Parma, Ugolino Hospital, Italy.

Amisulpride (50 mg o.d.) was compared with sertraline (50-100 mg o.d.) for 12
weeks in a double-blind, parallel-group study in 313 outpatients with dysthymia
(DSM-IV +/- episode of major depression). Full response rate [> or = 50%
decrease in Hamilton Depression Rating Scale (HAMD) total score] was higher with
amisulpride after 4 weeks (63% versus 50%, P < 0.02) and 8 weeks (82% versus
69%, P < 0.009). Time to initial improvement (> or = 25% decrease in HAMD total
score) and to > or = 50% HAMD decrease were significantly shorter with
amisulpride (P < 0.0033 and P < 0.0080, respectively). A faster response was
also present in the subgroup of patients with pure dysthymia. The improvement in
HAMD, Montgomery and Asberg Depression Rating Scale and Social and Occupational
Assessment Scale total scores, as well as Clinical Global Impression
improvement, was significantly greater with amisulpride after 4 weeks. Both
drugs were equally effective at week 12. The tolerability of both drugs was
satisfactory. Amisulpride is significantly more effective than sertraline during
the first weeks of treatment in dysthymia.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11712619 [PubMed – indexed for MEDLINE]

16: J Am Acad Child Adolesc Psychiatry. 2001 Sep;40(9):1070-8.

Phenomenology, psychosocial correlates, and treatment seeking in major
depression and dysthymia of adolescence.

Flament MF, Cohen D, Choquet M, Jeammet P, Ledoux S.

CNRS-UMR 7593, La Salpetriere Hospital, Paris, France. flament@ext.jussieu.fr

OBJECTIVE: To compare phenomenology, psychosocial correlates, and treatment
seeking in DSM-Itt-R major depression and dysthymia among adolescents diagnosed
as cases in a community-based study. METHOD: A self-report questionnaire,
including psychosocial data, life events, eating behaviors, depressive symptoms,
substance use, pathological behaviors, and family and school functioning was
administered to a nonselected sample (N = 3,287, 93.2% of targeted population)
of adolescents aged 11 to 20 years from several Haute-Marne communities in
France in 1988-1989. Subgroups of subjects (n = 205, 84.7% of eligible subjects)
were interviewed with a structured diagnostic schedule, and adolescents with
major depression (n = 49), dysthymia (n = 21) and controls (n = 135) were
compared. RESULTS: Nearly 30% of controls had at least one current symptom of
depression. Patterns of affective symptoms were similar in major depression and
dysthymia, but significant differences emerged in comorbid conditions (more
anxiety disorders, suicidal behaviors, and alcohol intoxications associated with
major depression) and stressor at onset (more severe in major depression).
Experiences of loss during the prior 12 months were associated with both forms
of affective disorder, while poor family relationships were specific correlates
of dysthymia. In contrast, peer relationships and pathological behaviors did not
differ between depressed subjects and controls. Although psychosocial
functioning was significantly impaired in both groups of depressed adolescents,
treatment seeking was limited to 34.7% for major depressive subjects and 23.8%
for dysthymic subjects. CONCLUSION: The results provide evidence that major
depression and dysthymia in adolescence are equally severe but may have distinct
patterns in associated factors. Despite free access to health care, the rate of
treatment seeking for mood disorders in France is similar to that reported in
U.S. studies.

PMID: 11556631 [PubMed – indexed for MEDLINE]

17: J Child Adolesc Psychopharmacol. 2001 Summer;11(2):131-42.

Sertraline effects in adolescent major depression and dysthymia: a six-month
open trial.

Nixon MK, Milin R, Simeon JG, Cloutier P, Spenst W.

Mental Health Patient Service Unit, Children’s Hospital of Eastern Ontario,
Ottawa, Canada. nixon@cheo.on.ca

This 6-month open-label study evaluated the efficacy, tolerability, and safety
of sertraline in 21 adolescent psychiatric outpatients, ages 12 to 18 years,
diagnosed with major depressive disorder (MDD, n = 13) or dysthymic disorder
(DD, n = 8). Both groups showed clinically significant improvements on the
Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale, and the Clinical
Global Impression Scale-Severity (CGI-S). The MDD group showed maximal clinical
response (based on the method of last observation carried forward) on the HAM-D
and CGI at weeks 12 (76.9%) and 20 (76.9%), respectively. Response rates were
maintained at week 24 with all six MDD study completers (100%) responding to
treatment. The DD group achieved maximal response on the HAM-D (100%) and the
CGI (75%) at week 6. Response rates in this group did not remain as elevated
over time with two out of three (66.7%) DD study completers responding to
treatment at week 24. Generally, sertraline was safe and well tolerated. Most
adverse events were mild to moderate in severity and resolved with no action
taken. Results suggest that sertraline may be efficacious in acute and
continuation treatment of MDD in adolescents. DD patients showed evidence of
clinical response and improvement, particularly in the acute treatment phase.
Incorporating a longer evaluation period in the study of antidepressant therapy
for adolescents with MDD and/or DD is emphasized.

Publication Types:
Clinical Trial

PMID: 11436952 [PubMed – indexed for MEDLINE]

18: J Affect Disord. 2001 May;64(2-3):231-7.

Maintenance desipramine for dysthymia: a placebo-controlled study.

Miller NL, Kocsis JH, Leon AC, Portera L, Dauber S, Markowitz JC.

Department of Psychiatry, Weill Medical College of Cornell University, New York,
NY 10128, USA. nlmill@cs.com

BACKGROUND: This study examines the efficacy of maintenance pharmacotherapy in
dysthymia without concurrent major depression, i.e. ‘pure dysthymia’. No
published data exist on this topic. METHODS: Responders to a 10-week open trial
of desipramine (DMI) whose therapeutic response persisted during a 4-month
continuation phase were eligible to begin a 2-year placebo-controlled
maintenance phase. We analyzed the subgroup with DSM-III-R pure dysthymia (n=27)
that entered maintenance. Time to recurrence during maintenance therapy was
compared between the two treatment groups. RESULTS: Six of 13 patients receiving
placebo and none of 14 patients receiving ongoing DMI experienced a recurrence.
Risk of recurrence was significantly greater for placebo patients. Five of six
placebo recurrences occurred within the first 6 months of maintenance.
LIMITATIONS: Larger replication studies are needed. CONCLUSION: Desipramine was
efficacious as a maintenance treatment in patients with pure dysthymia who
responded to 7 months of acute and continuation DMI.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11313089 [PubMed – indexed for MEDLINE]

19: J Fam Pract. 2001 May;50(5):405-12.

Comment in:
J Fam Pract. 2001 May;50(5):413.

Treatment of dysthymia and minor depression in primary care: a randomized trial
in patients aged 18 to 59 years.

Barrett JE, Williams JW Jr, Oxman TE, Frank E, Katon W, Sullivan M, Hegel MT,
Cornell JE, Sengupta AS.

Department of Community and Family Medicine, Dartmouth Medical School, Hanover,
NH 03755, USA. James.Barrett@Dartmouth.edu

OBJECTIVE: The researchers evaluated the effectiveness of paroxetine and
Problem-Solving Treatment for Primary Care (PST-PC) for patients with minor
depression or dysthymia. STUDY DESIGN: This was an 11-week randomized
placebo-controlled trial conducted in primary care practices in 2 communities
(Lebanon, NH, and Seattle, Wash). Paroxetine (n=80) or placebo (n=81) therapy
was started at 10 mg per day and increased to a maximum 40 mg per day, or PST-PC
was provided (n=80). There were 6 scheduled visits for all treatment conditions.
POPULATION: A total of 241 primary care patients with minor depression (n=114)
or dysthymia (n=127) were included. Of these, 191 patients (79.3%) completed all
treatment visits. OUTCOMES: Depressive symptoms were measured using the 20-item
Hopkins Depression Scale (HSCL-D-20). Remission was scored on the Hamilton
Depression Rating Scale (HDRS) as less than or equal to 6 at 11 weeks.
Functional status was measured with the physical health component (PHC) and
mental health component (MHC) of the 36-item Medical Outcomes Study Short Form.
RESULTS: All treatment conditions showed a significant decline in depressive
symptoms over the 11-week period. There were no significant differences between
the interventions or by diagnosis. For dysthymia the remission rate for
paroxetine (80%) and PST-PC (57%) was significantly higher than for placebo
(44%, P=.008). The remission rate was high for minor depression (64%) and
similar for each treatment group. For the MHC there were significant outcome
differences related to baseline level for paroxetine compared with placebo. For
the PHC there were no significant differences between the treatment groups.
CONCLUSIONS: For dysthymia, paroxetine and PST-PC improved remission compared
with placebo plus nonspecific clinical management. Results varied for the other
outcomes measured. For minor depression, the 3 interventions were equally
effective; general clinical management (watchful waiting) is an appropriate
treatment option.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11350703 [PubMed – indexed for MEDLINE]

20: Med Clin North Am. 2001 May;85(3):631-44.

Depression and dysthymia.

Moore JD, Bona JR.

Department of Psychiatry and Behavioral Sciences, Emory University School of
Medicine, Atlanta, Georgia, USA.

The advances made in the 1980s and 1990s have yielded many advances in the
diagnosis and treatment of depression and dysthymia. Skill of the clinician is
important in sorting out the diagnosis, taking care to consider the various
medical conditions that can cause depression or disguise themselves as
depression. Depressive disorders are highly treatable conditions. Clinicians
must overcome the stigma associated with these disorders to alleviate the pain
and suffering of those afflicted. The advances in treatment have been enormous
and continue to grow. The keys to these treatments lie in continuing to acquire
the knowledge to unlock all of the causes of depression. An appendix follows
listing medications commonly used in the treatment of depression or for other
conditions in patients under treatment for depression.

Publication Types:
Review

PMID: 11349477 [PubMed – indexed for MEDLINE]

21: J Psychother Pract Res. 2001 Spring;10(2):93-103.

Adding group psychotherapy to medication treatment in dysthymia: a randomized
prospective pilot study.

Hellerstein DJ, Little SA, Samstag LW, Batchelder S, Muran JC, Fedak M, Kreditor
D, Rosenthal RN, Winston A.

Department of Psychiatry, Beth Israel Medical Center, New York, USA.

Patients with dysthymia have been shown to respond to treatment with
antidepressant medications, and to some degree to psychotherapy. Even patients
successfully treated with medication often have residual symptoms and impaired
psychosocial functioning. The authors describe a prospective randomized 36-week
study of dysthymic patients, comparing continued treatment with antidepressant
medication (fluoxetine) alone and medication with the addition of group therapy
treatment. After an 8-week trial of fluoxetine, medication-responsive subjects
were randomly assigned to receive either continued medication only or medication
plus 16 sessions of manualized group psychotherapy. Results provide preliminary
evidence that group therapy may provide additional benefit to
medication-responding dysthymic patients, particularly in interpersonal and
psychosocial functioning.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11264333 [PubMed – indexed for MEDLINE]

22: Neuropsychobiology. 2001;44(3):139-49.

Insomnia related to dysthymia: polysomnographic and psychometric comparison with
normal controls and acute therapeutic trials with trazodone.

Saletu-Zyhlarz GM, Abu-Bakr MH, Anderer P, Semler B, Decker K, Parapatics S,
Tschida U, Winkler A, Saletu B.

Department of Psychiatry, University of Vienna, Austria.
gerda.saletu-zyhlarz@akh-wien.ac.at

Utilizing polysomnography (PSG) and psychometry, objective and subjective sleep
and awakening quality was investigated in 11 patients (mean age 50 +/- 14) with
nonorganic insomnia (F 51.0) related to dysthymia (F 34.1) as compared with 11
age- and sex-matched normal controls. Patients demonstrated decreased sleep
efficiency and sleep stage S2 as well as increased sleep latency to S1, S2 and
S3, wakefulness within the total sleep period, number of awakenings, S1 and REM
sleep. There was no intergroup difference in REM latency. Subjective sleep
quality and the total score of the Self-Assessment Scale for Sleep and Awakening
Quality (SSA) were deteriorated as were evening and morning well-being, mood,
affectivity and drowsiness. Noopsychic measures showed deteriorated numerical
memory, fine motor activity and reaction time variability. In a
placebo-controlled crossover design study, the acute effects of 100 mg
trazodone, a serotonin reuptake inhibitor with a sedative action due to 5HT(2)
and alpha(1) receptor blockade, were investigated in the patients. As compared
with placebo, trazodone induced an increase in slow-wave sleep (S3 + 4), a
lengthening of REM latency, a decrease in REM sleep and a normalization of the
periodic leg movement (PLM) index. In the morning, there was a minimal increase
in somatic complaints and a decrease in critical flicker frequency and systolic
blood pressure. In conclusion, our study demonstrated that dysthymia induced
significant changes in objective and subjective sleep and awakening quality,
which were counteracted by 100 mg trazodone, thus suggesting a key-lock
principle in the treatment of nonorganic insomnia related to dysthymia with this
drug. Copyright 2001 S. Karger AG, Basel

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11586054 [PubMed – indexed for MEDLINE]

23: Schweiz Rundsch Med Prax. 2000 Dec 21;89(51-52):2183-8.

[Treatment of dysthymia] [Article in German]

Poldinger W.

Hippocrates described both melancholy and dysthymia. An episode of mild
depression lasting up to 2 years, which does not make patients unfit to work,
although the repressive irritative mood disorder does reduce their ability to
work. Severe depressive moods can develop from dysthymia. While dysthymia
responds to antidepressant treatment similarly to depressive episodes, treatment
must be carried out for a considerably longer period. The dosage dose not differ
from that for severe depressive episodes. A few examples of cases are presented
from the speaker’s own cases to illustrate how well they responded to treatment
with St.-John’s wort.

Publication Types:
Review

PMID: 11197300 [PubMed – indexed for MEDLINE]

24: J Clin Psychiatry. 2000 Nov;61(11):821-7.

Treatment of dysthymia with sertraline: a double-blind, placebo-controlled trial
in dysthymic patients without major depression.

Ravindran AV, Guelfi JD, Lane RM, Cassano GB.

Department of Psychiatry, University of Ottawa, Ontario, Canada.

BACKGROUND: The selective serotonin reuptake inhibitor sertraline has been shown
to be efficacious and well tolerated for the treatment of major depressive
disorder. Relatively few trials, however, have examined the role of
pharmacotherapy in dysthymia without concurrent major depression. The current
investigation focuses on the use of sertraline for the treatment of dysthymia.
METHOD: In this 12-week, multicenter, double-blind study, 310 patients with a
DSM-III-R diagnosis of dysthymic disorder without concurrent major depression
were randomly assigned to receive either sertraline (N = 158) or placebo (N =
152). Sertraline was initiated at a dose of 50 mg daily, with titration
permitted to a maximum of 200 mg daily. The primary evaluation criteria were the
Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal
Affective Disorder Version (SIGH-SAD), the Montgomery-Asberg Depression Rating
Scale (MADRS), and the Clinical Global Impressions-Severity of Illness (CGI-S)
and -Improvement (CGI-I) scales. RESULTS: Mean percentage reductions for the
intent-to-treat population in SIGH-SAD scores were 44.6% for the
sertraline-treated group and 33.2% for the placebo-treated group (p = .03);
MADRS scores, 43.6% and 33.0% (p = .02); and CGI-S scores, 32.8% and 22.8% (p =
.02). A significantly greater proportion of the sertraline-treated group was
classified as responders (defined for HAM-D and MADRS scores as a 50% score
reduction and for CGI-I as a score of 1 or 2 by the final visit) and remitters
(SIGH-SAD score < or = 8) relative to the placebo-treated group by the final
visit. In addition, sertraline-treated patients experienced greater improvements
in all 9 domains of the Battelle Quality of Life Questionnaire than
placebo-treated patients did, with a significant difference observed in favor of
sertraline in 8 of the 9 domains. The life satisfaction and social interaction
quality of life domains showed significantly greater response in sertraline
responders compared with placebo SIGH-SAD responders. Sertraline was well
tolerated. Thirteen percent of the sertraline-treated group versus 8% of the
placebo-treated group withdrew from therapy owing to adverse events (p = .14).
CONCLUSION: Sertraline is efficacious and well tolerated in the short-term
treatment of dysthymia without concurrent major depression.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 11105734 [PubMed – indexed for MEDLINE]

25: JAMA. 2000 Sep 27;284(12):1519-26.

Comment in:
JAMA. 2000 Dec 20;284(23):2993-4; author reply 2994.
JAMA. 2000 Dec 20;284(23):2993; author reply 2994.
JAMA. 2000 Dec 20;284(23):2993; author reply 2994.
JAMA. 2000 Sep 27;284(12):1570-2.

Treatment of dysthymia and minor depression in primary care: A randomized
controlled trial in older adults.

Williams JW Jr, Barrett J, Oxman T, Frank E, Katon W, Sullivan M, Cornell J,
Sengupta A.

Ambulatory Care (11C-6), 7400 Merton Minter Blvd, San Antonio, TX 78284, USA.
jwilliam@verdict.uthscsa.edu

CONTEXT: Insufficient evidence exists for recommendation of specific effective
treatments for older primary care patients with minor depression or dysthymia.
OBJECTIVE: To compare the effectiveness of pharmacotherapy and psychotherapy in
primary care settings among older persons with minor depression or dysthymia.
DESIGN: Randomized, placebo-controlled trial (November 1995-August 1998).
SETTING: Four geographically and clinically diverse primary care practices.
PARTICIPANTS: A total of 415 primary care patients (mean age, 71 years) with
minor depression (n = 204) or dysthymia (n = 211) and a Hamilton Depression
Rating Scale (HDRS) score of at least 10 were randomized; 311 (74.9%) completed
all study visits. INTERVENTIONS: Patients were randomly assigned to receive
paroxetine (n = 137) or placebo (n = 140), starting at 10 mg/d and titrated to a
maximum of 40 mg/d, or problem-solving treatment-primary care (PST-PC; n = 138).
For the paroxetine and placebo groups, the 6 visits over 11 weeks included
general support and symptom and adverse effects monitoring; for the PST-PC
group, visits were for psychotherapy. MAIN OUTCOME MEASURES: Depressive
symptoms, by the 20-item Hopkins Symptom Checklist Depression Scale (HSCL-D-20)
and the HDRS; and functional status, by the Medical Outcomes Study Short-Form 36
(SF-36) physical and mental components. RESULTS: Paroxetine patients showed
greater (difference in mean [SE] 11-week change in HSCL-D-20 scores, 0.21 [0.
07]; P =.004) symptom resolution than placebo patients. Patients treated with
PST-PC did not show more improvement than placebo (difference in mean [SE] change in HSCL-D-20 scores, 0.11 [0.13]; P =.13), but their symptoms improved
more rapidly than those of placebo patients during the latter treatment weeks (P
=.01). For dysthymia, paroxetine improved mental health functioning vs placebo
among patients whose baseline functioning was high (difference in mean [SE] change in SF-36 mental component scores, 5.8 [2.02]; P =. 01) or intermediate
(difference in mean [SE] change in SF-36 mental component scores, 4.4 [1.74]; P
=.03). Mental health functioning in dysthymia patients was not significantly
improved by PST-PC compared with placebo (P>/=.12 for low-, intermediate-, and
high-functioning groups). For minor depression, both paroxetine and PST-PC
improved mental health functioning in patients in the lowest tertile of baseline
functioning (difference vs placebo in mean [SE] change in SF-36 mental component
scores, 4.7 [2.03] for those taking paroxetine; 4.7 [1.96] for the PST-PC
treatment; P =.02 vs placebo). CONCLUSIONS: Paroxetine showed moderate benefit
for depressive symptoms and mental health function in elderly patients with
dysthymia and more severely impaired elderly patients with minor depression. The
benefits of PST-PC were smaller, had slower onset, and were more subject to site
differences than those of paroxetine.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 11000645 [PubMed – indexed for MEDLINE]

26: Am J Psychiatry. 2000 Sep;157(9):1436-44.

Comment in:
Am J Psychiatry. 2002 Jan;159(1):156.

Double-blind comparison of sertraline, imipramine, and placebo in the treatment
of dysthymia: effects on personality.

Hellerstein DJ, Kocsis JH, Chapman D, Stewart JW, Harrison W.

Outpatient Mental Health Services, Beth Israel Medical Center, New York, NY
10003, USA. dhellerstein@bethisraelny.org

OBJECTIVE: Although previous studies have shown that dysthymia, or chronic
depression, commonly responds to antidepressant medications (with improvements
in depressive symptoms and psychosocial functioning), there have been no
systematic studies of the impact of antidepressant treatment on personality
variables in patients with this disorder. METHOD: In a multicenter study, 410
patients with early-onset primary dysthymia were treated in a randomized
prospective fashion with sertraline, imipramine, or placebo. The data were
analyzed in terms of the subjects’ scores on the Tridimensional Personality
Questionnaire, a 100-item self-report instrument that measures four
temperamental dimensions: harm avoidance, reward dependence, novelty seeking,
and persistence. RESULTS: At baseline, the harm avoidance scores of the
dysthymic subjects were approximately 1.5 standard deviations higher than those
of a previously reported community sample. After treatment, there was a
significant decrease in harm avoidance scores, with no significant between-group
differences. Remission of dysthymia was associated with significantly greater
improvement in harm avoidance, with the greatest numerical change found in the
patients treated with sertraline. Subjects’ Tridimensional Personality
Questionnaire scores were correlated at a 0.50 level with the Social Adjustment
Scale both pre- and posttreatment, suggesting that a high degree of harm
avoidance may be associated with poor social functioning. CONCLUSIONS: Before
treatment, chronically depressed patients demonstrate an abnormality in
temperament, as measured by elevated degrees of harm avoidance. Remission of
dysthymia is associated with improvement in this aspect of temperament.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 10964860 [PubMed – indexed for MEDLINE]

27: J Child Adolesc Psychopharmacol. 2000 Summer;10(2):103-9.

An open trial of paroxetine in the treatment of children and adolescents
diagnosed with dysthymia.

Nobile M, Bellotti B, Marino C, Molteni M, Battaglia M.

Child Psychiatry Unit, Istituto Scientifico Eugenio Medea, Bosisio Parini,
Italy. mnobile@bp.lnf.it

This open-label study examined the potential efficacy of paroxetine in the
treatment of children and adolescents diagnosed with dysthymia over a period of
3 months. Seven subjects were evaluated by the Hamilton Depression Rating Scale
(HAM-D), by the Clinical Global Impression Severity of Illness Scale (CGI-S),
and the Clinical Global Impression Improvement Scale (CGI-I). Seventy-one
percent of patients had a satisfactory response, suggesting the efficacy of
paroxetine in children with dysthymia.

Publication Types:
Clinical Trial

PMID: 10933120 [PubMed – indexed for MEDLINE]

28: Mol Psychiatry. 2000 May;5(3):242-61.

Dysthymia: a review of pharmacological and behavioral factors.

Griffiths J, Ravindran AV, Merali Z, Anisman H.

Department of Psychiatry, University of Ottawa, Ottawa, Canada.

Although dysthymia, a chronic, low-grade form of depression, has a morbidity
rate as high as that of major depression, and increases the risk for major
depressive disorder, limited information is available concerning the etiology of
this illness. In the present report we review literature concerning the
biological and characterological features of dysthymia, the effectiveness of
antidepressant treatments, the influence of stressors in the precipitation and
maintenance of the disorder, and both quality of life and psychosocial
correlates of the illness. We also provisionally suggest that dysthymia may stem
from disturbances of neuroendocrine and neurotransmitter functioning (eg,
corticotropin releasing hormone and arginine vasopressin within the
hypothalamus, or alternatively monoamine variations within several
extrahypothalamic sites), and may also involve cytokine activation. The central
disturbances may reflect phenotypic variations of neuroendocrine processes or
sensitization of such mechanisms. It is suggested that chronic stressor
experiences or stressors encountered early in life lead to the phenotypic
neurochemical alterations, which then favor the development of the dysthymic
state. Owing to the persistence of the neurochemical disturbances, vulnerability
to double depression is increased, and in this instance treatment with
antidepressants may attenuate the symptoms of major depression but not those of
the basal dysthymic state. Moreover, the residual features of depression
following treatment may be indicative of underlying neurochemical disturbances,
and may also serve to increase the probability of illness recurrence or relapse.

Publication Types:
Review

PMID: 10889527 [PubMed – indexed for MEDLINE]

29: J Child Adolesc Psychopharmacol. 2000 Spring;10(1):9-18.

Therapeutic effects and tolerability of fluvoxamine treatment in adolescents
with dysthymia.

Rabe-Jablonska J.

II Department of Psychiatry, Medical University of Lodz, Poland.
polbvasi@post.ld.onet.pl

OBJECTIVE: The aim of the study was to evaluate therapeutic effects and
tolerability of fluvoxamine (150-200 mg daily) in 21 dysthymic adolescents.
SUBJECTS: Twenty-one adolescents, attending psychiatric clinics, who met
DSM-III-R criteria for dysthymia, without significant co-morbidity were the
subjects. METHODS: Axis I and II diagnoses were made by using SCID-P and SCID
II. Score A of >13 on HAMD-S at baseline was mandatory. The HAMD-S was completed
after 4, 8, and 26 weeks. Adverse effects were recorded after 1, 2, 4, and 8,
weeks. Tolerability was assessed by using CGI-T after 1, 2, and 4 weeks. Adverse
effects caused three subjects to withdraw from the study. RESULTS: Good clinical
response (decrease of HAMD-S score >50%) was observed after 4 weeks in 48% of
patients; after 8 weeks in 56% of patients, and after 26 weeks in 44% patients.
Relapse occurred in 34% of subjects. Fluvoxamine was well tolerated in 76.2% of
the adolescents; poor toleration resulted in its discontinuation in 14.2%
adolescents.

Publication Types:
Clinical Trial

PMID: 10755577 [PubMed – indexed for MEDLINE]

30: Cochrane Database Syst Rev. 2000;(4):CD001130.

Update of:
Cochrane Database Syst Rev. 2000;(2):CD001130.

Drugs versus placebo for dysthymia.

Lima MS, Moncrieff J.

Department of Mental Health, Universidade Federal de Pelotas, Avenida Duque de
Caxias, 250, Pelotas, Rio Grande do Sul, BRAZIL, 96100. mslima@nutecnet.com.br

OBJECTIVES: Dysthymia is a depressive disorder of chronic nature but of less
severity than major depression, which depressive symptoms are more or less
continuous for at least two years. The aim of this review was to conduct a
systematic review of all RCTs comparing drugs and placebo for dysthymia. SEARCH
STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT,
Biological Abstracts and LILACS; reference searching; personal communication;
conference abstracts; unpublished trials from the pharmaceutical industry; book
chapters on the treatment of depression. SELECTION CRITERIA: The inclusion
criteria for all randomised controlled trials were that they should focus on the
use of drugs versus placebo for dysthymic patients. Exclusion criteria were: non
randomised, mixed major depression/ dysthymia (trials not providing separate
data) and depression secondary to other disorders (e.g. substance abuse). DATA
COLLECTION AND ANALYSIS: The reviewers extracted the data independently. In
order to achieve an intention-to-treat analysis, when trials failed to report it
was assumed that people who died or dropped out had no improvement. Authors of
relevant trials were contacted for additional and missing data. Absence of
treatment response as defined by authors was the main measure of outcome used.
Relative Risks (RR) and 95% confidence intervals (CI) of dichotomous data were
calculated with the Random Effects Model. Where possible, number needed to treat
(NNT) and number needed to harm (NNH) were estimated, taking the reciprocal of
the absolute risk reduction. MAIN RESULTS: Currently the review includes 15
trials. Similar results were obtained in terms of efficacy for different groups
of drugs, such as tricyclic (TCA), selective serotonin reuptake inhibitors
(SSRI), monoamine oxidase inhibitors (MAOI) and other drugs (sulpiride,
amineptine, and ritanserin). The pooled RR for absence of treatment response was
0.68 (95% CI 0.59-0.78) for TCA and the NNT was 4.3 (95% CI 3.2-6.5). SSRIs
showed similar RR for this outcome: 0.64 (95% CI 0.55-0.74), the NNT being 4.7
(95% CI 3.5-6.9). Concerning MAOIs, the RR was 0.59 (95% CI 0.48-0.71) and the
NNT was 2.9 (95% CI 2.2-4.3). Other drugs (amisulpride, amineptine and
ritanserin) showed similar results in terms of absence of treatment response.
Using more stringent criteria for improvement – full remission – the results
were unchanged. Patients treated on TCA were more likely to report adverse
events, compared with placebo. REVIEWER’S CONCLUSIONS: Drugs are effective in
the treatment of dysthymia with no differences between and within class of
drugs. Tricyclic antidepressants are more likely to cause adverse events and
dropouts. As dysthymia is a chronic condition, there remains little information
on quality of life and medium or long-term outcome.

Publication Types:
Review

PMID: 11034701 [PubMed – indexed for MEDLINE]

31: Cochrane Database Syst Rev. 2000;(2):CD001130.

Update in:
Cochrane Database Syst Rev. 2000;(4):CD001130.

A comparison of drugs versus placebo for the treatment of dysthymia.

Lima MS, Moncrieff J.

Department of Mental Health, Universidade Federal de Pelotas, Avenida Duque de
Caxias, 250, Pelotas, Rio Grande do Sul, Brazil, 96100. mslima@nutecnet.com.br

OBJECTIVES: Dysthymia is a depressive disorder of chronic nature but of less
severity than major depression, which depressive symptoms are more or less
continuous for at least two years. The aim of this review was to conduct a
systematic review of all RCTs comparing drugs and placebo for dysthymia. SEARCH
STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT,
Biological Abstracts and LILACS; reference searching; personal communication;
conference abstracts; unpublished trials from the pharmaceutical industry; book
chapters on the treatment of depression. SELECTION CRITERIA: The inclusion
criteria for all randomised controlled trials were that they should focus on the
use of drugs versus placebo for dysthymic patients. Exclusion criteria were: non
randomised, mixed major depression/ dysthymia (trials not providing separate
data) and depression secondary to other disorders (e.g. substance abuse). DATA
COLLECTION AND ANALYSIS: The reviewers extracted the data independently. In
order to achieve an intention-to-treat analysis, when trials failed to report it
was assumed that people who died or dropped out had no improvement. Authors of
relevant trials were contacted for additional and missing data. Absence of
treatment response as defined by authors was the main measure of outcome used.
Relative Risks (RR) and 95% confidence intervals (CI) of dichotomous data were
calculated with the Random Effects Model. Where possible, number needed to treat
(NNT) and number needed to harm (NNH) were estimated, taking the reciprocal of
the absolute risk reduction. MAIN RESULTS: Currently the review includes 15
trials. Similar results were obtained in terms of efficacy for different groups
of drugs, such as tricyclic (TCA), selective serotonin reuptake inhibitors
(SSRI), monoamine oxidase inhibitors (MAOI) and other drugs (sulpiride,
amineptine, and ritanserin). The pooled RR for absence of treatment response was
0. 68 (95% CI 0.59-0.78) for TCA and the NNT was 4.3 (95% CI 3.2-6.5). SSRIs
showed similar RR for this outcome: 0.64 (95% CI 0.55-0.74), the NNT being 4.7
(95% CI 3.5-6.9). Concerning MAOIs, the RR was 0. 59 (95% CI 0.48-0.71) and the
NNT was 2.9 (95% CI 2.2-4.3). Other drugs (amisulpride, amineptine and
ritanserin) showed similar results in terms of absence of treatment response.
Using more stringent criteria for improvement – full remission – the results
were unchanged. Patients treated on TCA were more likely to report adverse
events, compared with placebo. REVIEWER’S CONCLUSIONS: Drugs are effective in
the treatment of dysthymia with no differences between and within class of
drugs. Tricyclic antidepressants are more likely to cause adverse events and
dropouts. As dysthymia is a chronic condition, there remains little information
on quality of life and medium or long-term outcome.

Publication Types:
Review

PMID: 10796749 [PubMed – indexed for MEDLINE]

32: Int Clin Psychopharmacol. 2000 Jan;15(1):43-8.

The efficacy and tolerability of venlafaxine and paroxetine in outpatients with
depressive disorder or dysthymia.

Ballus C, Quiros G, De Flores T, de la Torre J, Palao D, Rojo L, Gutierrez M,
Casais L, Riesgo Y.

Hospital Clinico, Barcelona, pain.

A 24-week, double-blind, randomized trial was performed to compare the efficacy
and tolerability of venlafaxine and paroxetine in patients with major depression
or dysthymia. Outpatients aged 18-70 years with a baseline score of 17 on the
21-item Hamilton Depression Rating Scale (HAM-D) were eligible. Patients were
randomly assigned to venlafaxine, 37.5 mg, in the morning and evening or
paroxetine, 20 mg, in the morning and placebo in the evening, which could be
increased to venlafaxine, 75 mg twice daily, or paroxetine, 20 mg twice daily,
after 4 weeks. Efficacy was assessed with the 21-item HAM-D, the
Montgomery-Asberg Rating Scale, the Hamilton Anxiety Rating Scale, and the
Clinical Global Impressions Scale. Forty-one patients were randomized to
venlafaxine and 43 to paroxetine. At week 6, a response was observed in 55% of
patients on venlafaxine and 29% on paroxetine (P = 0.03). At week 12,
significantly (P = 0.011) more patients in the venlafaxine group had a HAM-D
remission score of 8 or less (59% versus 31%). Discontinuation for any reason
occurred in 16 (39%) patients on venlafaxine and 11 (26%) on paroxetine. The
most common adverse events were nausea (28%), headache (18%) and dry mouth (15%)
with venlafaxine and headache (40%) and constipation (16%) with paroxetine.
Venlafaxine was effective and well tolerated for the treatment of patients with
mild to moderate depression or dysthymia. A consistently higher proportion of
patients had a response or remission on venlafaxine than on paroxetine.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 10836286 [PubMed – indexed for MEDLINE]

33: J Clin Psychiatry. 1999 Dec;60(12):845-9.

Venlafaxine in the treatment of dysthymia: an open-label study.

Hellerstein DJ, Batchelder ST, Little SA, Fedak MJ, Kreditor D, Rosenthal J.

Department of Psychiatry, Beth Israel Medical Center, New York, NY, USA.
DHellerstein@BethIsraelNY.org

BACKGROUND: Numerous studies have demonstrated the effectiveness of
antidepressant medications in the treatment of dysthymia, or chronic mild
depression. Venlafaxine blocks reuptake of both serotonin and norepinephrine and
may produce a more complete antidepressant response than do single-mechanism
selective serotonin reuptake inhibitors. The purpose of this open-label study
was to provide preliminary data on the tolerability and effectiveness of
venlafaxine for patients with dysthymia. METHOD: Twenty-two dysthymic subjects
(DSM-III-R criteria) were enrolled in this 10-week, open-label trial, and 5
dropped out prior to their second visit. Seventeen subjects (77.3%) received
more than 1 week of medication. RESULTS: Of these 17 subjects, 13 (76.5%) were
treatment responders. Results of paired sample t tests were highly significant,
indicating that, on average, there was significant improvement on all measures
of symptomatology and functioning, with mean +/- SD scores on the Hamilton
Rating Scale for Depression decreasing from 20.95 +/- 6.50 at baseline to 6.06
+/- 5.49 at week 10. The mean +/- SD final dose was 178.68 +/- 70.80 mg/day.
Side effects were reported by 17 (85%) of the 20 subjects for whom tolerability
was assessed (the most common were fatigue, dry mouth, and nausea); 5 (22.7%) of
22 patients discontinued treatment because of side effects, primarily nausea (N
= 3). CONCLUSION: These findings suggest the benefit of venlafaxine in the
treatment of chronic depression and the need for more rigorous studies.

Publication Types:
Clinical Trial

PMID: 10665631 [PubMed – indexed for MEDLINE]

34: Psychol Med. 1999 Nov;29(6):1273-89.

The efficacy of drug treatments for dysthymia: a systematic review and
meta-analysis.

de Lima MS, Hotoph M, Wessely S.

Departamento de Saude Mental, Faculdade de Medicina, Universidade Federal de
Pelotas, RS, Brazil.

BACKGROUND: Dysthymia is a common mental disorder, associated with considerable
disability and high co-morbidity. This review assessed the role of
pharmacological treatment. METHODS: All randomized-controlled trials that
compared active drug versus placebo for dysthymic patients were included. Pooled
relative risks (RR) and 95% confidence intervals (CI) were calculated with the
Random Effect Model method. Where possible, number needed to treat and number
needed to harm were estimated. RESULTS: Fifteen trials were included for the
main comparisons. Similar results were obtained in terms of efficacy for
different groups of drugs, such as tricyclic (TCA), selective serotonin reuptake
inhibitors (SSRI), monoamine oxidase inhibitors (MAOI) and other drugs
(sulpiride, amineptine, and ritanserin). The pooled RR treatment response was
0.68 (95% CI 0.59-0.78) for TCA, 0.64 (95% CI 0.55-0.74) for SSRIs, 0.59 (95% CI
0.48-0.71) for MAOIs. Other drugs (amisulpride, amineptine and ritanserin)
showed similar results. Patients treated on TCA were more likely to report
adverse events, compared with placebo. There were no differences in response to
active treatment when dysthymia was compared to either dysthymia plus major
depression or briefer non-major depressive states. CONCLUSIONS: Drug treatment
appears to be effective in the short-term management of dysthymic disorder. The
choice of drug should take into account specific side-effects profile of each
drug.

Publication Types:
Meta-Analysis

PMID: 10616934 [PubMed – indexed for MEDLINE]

35: Am J Psychiatry. 1999 Oct;156(10):1608-17.

Treatment of primary dysthymia with group cognitive therapy and pharmacotherapy:
clinical symptoms and functional impairments.

Ravindran AV, Anisman H, Merali Z, Charbonneau Y, Telner J, Bialik RJ, Wiens A,
Ellis J, Griffiths J.

Institute of Mental Health Research at Royal Ottawa Hospital, Ont., Canada.

OBJECTIVE: This study assessed the efficacy of antidepressant treatment
(sertraline) and group cognitive behavior therapy, alone or in combination, in
primary dysthymia. The clinical features of dysthymia, as well as the functional
impairments associated with the illness (e.g., quality of life, stress
perception, coping styles), were evaluated. METHOD: Patients (N = 97) diagnosed
with primary dysthymia, but no other current comorbid disorder, received either
sertraline or placebo in a double-blind design over 12 weeks. In addition, a
subgroup of the patients (N = 49) received a structured, weekly group cognitive
behavior therapy intervention. RESULTS: Treatment with sertraline, with or
without group cognitive behavior therapy, reduced the functional impairment of
depression. The reductions were similar in the drug-cognitive therapy group and
in subjects who received the drug alone. Furthermore, while group cognitive
behavior therapy alone reduced the depression scores, this effect was not
significantly greater than the effect of the placebo. The drug treatment also
induced pronounced improvement in the functional measures, and in some respects
these effects were augmented by group cognitive behavior therapy. Among patients
who responded favorably to cognitive behavior therapy, the improvements in the
functional measures were similar to those who responded to drug treatment,
whereas such functional changes were not seen among patients who responded to
placebo. CONCLUSIONS: Sertraline treatment effectively reduces the clinical
symptoms and functional impairments associated with dysthymia. Although the
group cognitive behavior therapy intervention was less effective in alleviating
clinical symptoms, it augmented the effects of sertraline with respect to some
functional changes, and in a subgroup of patients it attenuated the functional
impairments characteristic of dysthymia.

Publication Types:
Clinical Trial
Controlled Clinical Trial
Randomized Controlled Trial

PMID: 10518174 [PubMed – indexed for MEDLINE]

36: Psychiatry Clin Neurosci. 1999 Oct;53 Suppl:S49-53.

A pharmacotherapy algorithm for the treatment of dysthymia in Japan.

Kitamura H, Yokoyama T, Someya T.

Department of Psychiatry, Niigata University School of Medicine, Niigata City,
Japan.

Based on randomized controlled trials conducted in western countries, we
proposed a pharmacotherapy algorithm for DSM-IV dysthymia in Japan. The main
strategy of the algorithm are: firstly, one of the antidepressants is selected
for an initial agent, and secondly, efficacy of the selected antidepressant is
evaluated at 8 to 12 weeks. The agent with sufficient efficacy is continued for
at least 6 months, while ineffective agent is replaced to another
antidepressant. The algorithm is preliminary mainly because of the lack of data
from Japanese samples and the unavailability of some useful agents in Japan, for
instance, selective serotonin reuptake inhibitors and monoamine oxidase
inhibitors.

Publication Types:
Review

PMID: 10560899 [PubMed – indexed for MEDLINE]

37: J Affect Disord. 1999 Aug;54(3):283-6.

Six months of desipramine for dysthymia: can dysthymic patients achieve normal
social functioning?

Friedman RA, Markowitz JC, Parides M, Gniwesch L, Kocsis JH.

The New York Hospital, Cornell Medical Center, NY 10021, USA.

BACKGROUND: There is evidence that antidepressant medication improves social
dysfunction during acute treatment in dysthymic patients but it is unknown if
the gain in social functioning persists or progresses with longer-term
antidepressant treatment. We examine the effect of 6 months of desipramine
treatment on social functioning in dysthymic patients. METHODS: Forty-six
subjects with DSM-III-R dysthymia (70% with superimposed major depression) who
had responded to 10 weeks of open-label desipramine (DMI) treatment received 16
additional weeks of continuation DMI. Social functioning was measured at weeks
0, 10 and 26 with the Social Adjustment Scale-Self Report. RESULTS: Euthymia was
maintained and a marginally significant trend for further improvement in overall
social functioning appeared during continuation treatment. Only 24% of subjects
achieved normative level of social adjustment after 6 months of DMI treatment.
LIMITATIONS: The main limitation was the lack of a placebo control group.
CONCLUSION: Acute improvement in social functioning persists during continuation
treatment. However, most dysthymic patients did not achieve a community level of
social adjustment. Significant social dysfunction persists in dysthymic patients
with low levels of depressive symptomatology after 6 months of intense DMI
treatment.

Publication Types:
Clinical Trial

PMID: 10467972 [PubMed – indexed for MEDLINE]

38: J Clin Psychiatry. 1999 Aug;60(8):508-18.

The long-term outcome of dysthymia in private practice: clinical features,
temperament, and the art of management.

Haykal RF, Akiskal HS.

Charter Lakeside Behavioral Health System, University of Tennessee, Memphis,
USA.

BACKGROUND: With the clinical availability of fluoxetine in the United States,
we were interested in documenting improvements in the clinical care of dysthymic
patients beyond what was reported from our clinic 2 decades earlier during the
“tricyclic (TCA) era.” METHOD: In open treatment of 42 consecutive DSM-III-R
primary dysthymic patients who were personally followed up in our mood clinic
since 1988, response was defined as sustained remission, i.e., no longer meeting
criteria for dysthymia and achieving DSM-III-R Axis V Global Assessment of
Functioning (GAF) score > 70 throughout much of the mean follow-up of 5 years.
RESULTS: Compared to patients with nondysthymic episodic major depressive
disorder (N = 42), dysthymic patients had a significantly earlier mean age at
onset (12.6 vs. 34 years), were more likely to have never been married, had a
greater frequency of superimposed major depressive episodes (except for the 14%
[N = 6] with “pure” dysthymia), and had more psychiatric and fewer medical
comorbidities; furthermore, patients with dysthymia had significantly greater
familial loading of both unipolar and bipolar disorders. Continued treatment
with TCA-type antidepressants or fluoxetine (including various augmenting
strategies) led to an overall robust and sustained response rate of 76% (N = 32)
among dysthymic patients; in tandem, major depressive episodes and suicidality
were prevented in all responders. Females treated with fluoxetine had the
highest response rate (85% [N = 17]); some were able to walk out of dependent
abusive relationships for the first time in their lives. However, dramatic
responses with “hyperthymic” switches in temperament occurred in only 12% of
dysthymic patients; nearly all were males with bipolar family history. The more
prototypic positive change among dysthymic responders consisted of coping with
daily hassles without being overwhelmed. Qualitatively, the highest level of
adaptive functioning was observed among fluoxetine-treated dysthymics (50% of
responders [N = 12] achieved DSM-III-R GAF score of 81-90). Of TCA-treated
patients, 39% had intolerable side effects, necessitating switch-over to
fluoxetine. Agitation occurred in 11% of fluoxetine-treated patients (N = 4) and
was associated with nonresponse and/or dropout; otherwise, this selective
serotonin reuptake inhibitor was well tolerated, thereby contributing to
long-term compliance. More provocatively, patients with dysthymia who had
required extensive psychotherapeutic attention prior to state-of-the-art
pharmacotherapy no longer required such therapy. CONCLUSION: These data extend
and enrich what has been learned from controlled trials among dysthymic
patients. With sustained pharmacotherapy and specialized clinical care in a
private mood clinic, 3 of 4 patients immersed in gloom for much of their lives
achieved for the first time good to superior levels of functioning that were
maintained for an average of 5 years. Although the art of clinical management of
dysthymia should be fully grounded in understanding the interpersonal context of
depression, we submit that SSRIs such as fluoxetine appear broadly efficacious
in areas previously deemed to be the domain of formal psychotherapy.

Publication Types:
Case Reports
Clinical Trial

PMID: 10485632 [PubMed – indexed for MEDLINE]

39: Gen Hosp Psychiatry. 1999 Jul-Aug;21(4):260-73.

The treatment effectiveness project. A comparison of the effectiveness of
paroxetine, problem-solving therapy, and placebo in the treatment of minor
depression and dysthymia in primary care patients: background and research plan.

Barrett JE, Williams JW Jr, Oxman TE, Katon W, Frank E, Hegel MT, Sullivan M,
Schulberg HC.

Department of Community and Family Medicine, Dartmouth Medical School, Hanover,
NH 03755, USA.

This report describes the background, rationale, and research plan for a
comparative treatment trial of the effectiveness of paroxetine, problem-solving
therapy (PST-PC), and placebo in the treatment of minor depression and dysthymia
in primary care patients. Patients were recruited from a variety of primary care
practice settings in four separate geographic locations (Hanover, New Hampshire;
Pittsburgh, Pennsylvania, San Antonio, Texas; and Seattle, Washington). Patients
were randomly assigned to each of the three intervention conditions the
medication/placebo conditions were double-blinded. The treatment trial was 11
weeks, with independent assessments of patient clinical status at baseline, 6
weeks, and 11 weeks. There was a follow-up at 25 weeks. Since there are
relatively few placebo-controlled trials in primary care settings on patients
with these disorders, the background of this project and a description of it are
presented at this time, prior to the availability of outcome data, to provide
methodological detail and to increase awareness in the research community of
this treatment trial, with results to appear subsequently.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Review

PMID: 10514950 [PubMed – indexed for MEDLINE]

40: Biol Psychiatry. 1999 Jun 15;45(12):1533-41.

Comment in:
Biol Psychiatry. 1999 Jun 15;45(12):1531-2.

Dehydroepiandrosterone treatment of midlife dysthymia.

Bloch M, Schmidt PJ, Danaceau MA, Adams LF, Rubinow DR.

Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda,
MD 20892-1276, USA.

BACKGROUND: This study evaluated the efficacy of the adrenal androgen,
dehydroepiandrosterone, in the treatment of midlife-onset dysthymia. METHODS: A
double-blind, randomized crossover treatment study was performed as follows: 3
weeks on 90 mg dehydroepiandrosterone, 3 weeks on 450 mg dehydroepiandrosterone,
and 6 weeks on placebo. Outcome measures consisted of the following.
Cross-sectional self-ratings included the Beck Depression Inventory, and visual
analogue symptom scales. Cross-sectional objective ratings included the Hamilton
Depression Rating Scale, the Cornell Dysthymia Scale and a cognitive test
battery. Seventeen men and women aged 45 to 63 years with midlife-onset
dysthymia participated in this study. Response to dehydroepiandrosterone or
placebo was defined as a 50% reduction from baseline in either the Hamilton
Depression Rating Scale or the Beck Depression Inventory. RESULTS: In 15
patients who completed the study, a robust effect of dehydroepiandrosterone on
mood was observed compared with placebo. Sixty percent of the patients responded
to dehydroepiandrosterone at the end of the 6-week treatment period compared
with 20% on placebo. A significant response was seen after 3 weeks of treatment
on 90 mg per day. The symptoms that improved most significantly were anhedonia,
loss of energy, lack of motivation, emotional “numbness,” sadness, inability to
cope, and worry. Dehydroepiandrosterone showed no specific effects on cognitive
function or sleep disturbance, although a type II error could not be ruled out.
CONCLUSIONS: This pilot study suggests that dehydroepiandrosterone is an
effective treatment for midlife-onset dysthymia.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 10376113 [PubMed – indexed for MEDLINE]

41: Biol Psychiatry. 1999 Jan 15;45(2):229-33.

Treatment of refractory chronic depression and dysthymia with high-dose
thyroxine.

Rudas S, Schmitz M, Pichler P, Baumgartner A.

Community Mental Health Service of Vienna, Austria.

BACKGROUND: An 8-week open trial was conducted to investigate whether patients
with treatment-resistant, chronic depression and/or dysthymia could profit from
high-dose thyroxine (T4) augmentation. METHODS: Nine patients whose current
depressive episode had lasted for a mean of 15.5 +/- 8.6 months (range: 2-30
months) received T4 in addition to their current medication. RESULTS: Two
patients dropped out of the study owing to side effects. The remaining 7
patients received a final mean dose of T4 of 235 +/- 58 micrograms/day (range:
150-300 micrograms/day). Their scores on the Hamilton Depression Rating Scale
had fallen from a mean of 21.1 +/- 4.1 before inclusion in the study to a mean
of 8.0 +/- 2.8 at the end of the 8th week. Five patients were full responders, 1
a partial responder, and 1 a nonresponder. CONCLUSIONS: Augmentation with
high-dose T4 proved to have an antidepressant effect in more than 50% of the
previously treatment-resistant patients with chronic depression and/or
dysthymia.

Publication Types:
Clinical Trial

PMID: 9951571 [PubMed – indexed for MEDLINE]

42: J Affect Disord. 1999 Jan-Mar;52(1-3):275-90.

Dysthymia: clinical picture, extent of overlap with chronic fatigue syndrome,
neuropharmacological considerations, and new therapeutic vistas.

Brunello N, Akiskal H, Boyer P, Gessa GL, Howland RH, Langer SZ, Mendlewicz J,
Paes de Souza M, Placidi GF, Racagni G, Wessely S.

Center of Neuropharmacology, Institute of Pharmacological Sciences, University
of Milan, Italy. brunello@isfunix.farma.unimi.it

Dysthymia, as defined in the American Psychiatric Association and International
Classification of Mental Disorders, refers to a prevalent form of subthreshold
depressive pathology with gloominess, anhedonia, low drive and energy, low
self-esteem and pessimistic outlook. Although comorbidity with panic, social
phobic, and alcohol use disorders has been described, the most significant
association is with major depressive episodes. Family history is loaded with
affective, including bipolar, disorders. The latter finding explains why
dysthymia, especially when onset is in childhood, can lead to hypomanic
switches, both spontaneously and upon pharmacologic challenge in as many as 30%.
Indeed, antidepressants from different classes -tricyclic antidepressants
(TCAs), monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine
oxidase A (RIMAs), selective serotonin-reuptake inhibitors (SSRIs) and, more
recently, amisulpride, and spanning noradrenergic, serotonergic as well as
dopaminergic mechanisms of action – have been shown to be effective against
dysthymia in an average of 65% of cases. This is a promising development because
social and characterologic disturbances so pervasive in dysthymia often, though
not always, recede with continued pharmacotherapy beyond acute treatment.
Despite symptomatic overlap of dysthymia with chronic fatigue syndrome –
especially with respect to the cluster of symptoms consisting of low drive,
lethargy, lassitude and poor concentration – neither the psychopathologic
status, nor the pharmacologic response profile of the latter syndrome is
presently understood. Chronic fatigue today is where dysthymia was two decades
ago. We inverted question mark submit that the basic science – clinical paradigm
that has proven so successful in dysthymia could, before too long, crack down
the conundrum of chronic fatigue as well. At a more practical level, we raise
the possibility that a subgroup within the chronic fatigue group represents a
variant of dysthymia.

Publication Types:
Review

PMID: 10357046 [PubMed – indexed for MEDLINE]

43: J Psychopharmacol. 1999;13(3):248-54.

Amisulpride in medium-term treatment of dysthymia: a six-month, double-blind
safety study versus amitriptyline. AMILONG investigators.

Ravizza L.

Department of Neuroscience, School of Medicine, University of Torino, Italy.

Two hundred and fifty patients participated in a 6-month, double-blind study to
evaluate safety and efficacy of a medium-term treatment with amisulpride 50
mg/day versus amitriptyline 25-75 mg/day in dysthymia. Patients in treatment
groups (165 amisulpride; 85 amitriptyline) were well balanced for demographic
and baseline characteristics. A total of 139 patients (93 amisulpride, 46
amitriptyline) completed the study with no statistically significant differences
in reasons for premature termination between the two groups. A tendency towards
a higher incidence of treatment-emergent adverse events with amitriptyline was
observed (73% versus 64% amisulpride). In the amitriptyline group, a
statistically significantly higher incidence of central nervous system (41%
versus 24%, p=0.004) and autonomic nervous system disorders (45% versus 16%, p <
0.0001) was reported. Conversely, endocrine disorders were more frequent with
amisulpride (18% versus 7%, p=0.023). Efficacy was a secondary end-point.
Results of the symptom rating scales indicate that both drugs were equally
effective: 60% and 62% of patients under amisulpride and amitriptyline,
respectively, achieved a reduction > or = 50% of the Montgomery and Asberg
Rating Scale total score at end-point. On the item ‘global improvement’ of the
Clinical Global Impression, 67% of amisulpride and 68% of amitriptyline patients
were rated as ‘very much’ or ‘much’ improved. Results of the present study in a
large patient population further confirm the safe use of amisulpride in
dysthymia and support its administration upon a medium-term treatment period.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 10512080 [PubMed – indexed for MEDLINE]

44: Neuropsychobiology. 1999;39(1):25-32.

Amisulpride versus amineptine and placebo for the treatment of dysthymia.

Boyer P, Lecrubier Y, Stalla-Bourdillon A, Fleurot O.

Unite INSERM 302, Hopital Salpetriere, Paris, France.

Amisulpride, a selective antagonist for D2 and D3 dopamine receptors, acts
preferentially on presynaptic receptors increasing dopaminergic transmission at
low doses. In a multicentre, 3-month, placebo-controlled study, amisulpride (50
mg/day) was compared to amineptine (200 mg/day) in the treatment of primary
dysthymia. A total of 323 patients were enrolled. Amisulpride and amineptine
were found to be statistically superior to placebo (p < 0.0001) on the Clinical
Global Impression (item 2): 63, 64 and 33% responders, respectively; improvement
of Montgomery-Asberg Depression Rating Scale and Scale for the Assessment of
Negative Symptoms scores following amisulpride or amineptine treatment was twice
as high as with placebo (p < 0.0001). The adverse event profile of amisulpride
was similar to that of placebo except for endocrine symptoms in female patients;
amineptine showed mainly events linked to psychic activation (insomnia,
nervousness). Results show that amisulpride can improve symptoms of chronic
depression in dysthymia.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 9892856 [PubMed – indexed for MEDLINE]

45: Wien Med Wochenschr. 1999;149(18):503-10.

[Dysthymia: a chronic illness and its treatment] [Article in German]

Aschauer HN.

Klinischen Abteilung fur Allgemeine Psychiatrie, Universitatsklinik fur
Psychiatrie, Wien. Harald.Aschauer@akh-wien.ac.at

Dysthymia is a chronic disease with a high psychosocial burden. Age of onset
frequently is in young adulthood. It is clinically characterized by very mild
but continuous chronic depressive symptoms. The quality of symptoms seems to be
similar to episodic depressive disorders, but the severity criteria for major
depression are not fulfilled. After more than 2 years of dysthymia a depressive
episode may occur (double depression). Neurobiological and genetic findings
indicate a relation of dysthymia to affective disorders. Antidepressants are
proven to be effective without a difference between various types of drugs.

Psychotherapy is also proven to be effective (e.g. behaviour therapy) and should
be prescribed in combination or alone, if a patient refused to take drugs.
Because of the preferable side-effect profile of newer antidepressant compounds,
they should be prescribed as first choice. A prophylactic treatment for 2 years
is recommended. The dose of antidepressants should be in the therapeutic range
for treatment of major depression.

Publication Types:
Review

PMID: 10637954 [PubMed – indexed for MEDLINE]

46: Am J Psychiatry. 1998 Nov;155(11):1556-60.

Comorbid dysthymia and substance disorder: treatment history and cost.

Westermeyer J, Eames SL, Nugent S.

Minneapolis VA Medical Center, University of Minnesota 55417, USA.

OBJECTIVE: The purpose of this study was to determine the treatment history and
cost of previous treatment among patients with comorbid substance-related
disorder and dysthymia, as compared to patients with substance-related disorder
only. METHOD: Retrospective data were obtained regarding past treatment.
Treatment cost was calculated on the basis of the 1996 cost of various treatment
modalities. The setting was alcohol-drug programs located within departments of
psychiatry in two centers. A total of 642 patients were assessed, of whom 39 had
substance-related disorder and dysthymia and 308 had substance-related disorder
only (the remaining patients had other comorbid conditions). Data collection
instruments included an interview-based questionnaire regarding previous
psychiatric and substance abuse treatment. Current cost of treatment in various
settings was assessed on the basis of a survey of facilities used by patients in
this area. RESULTS: Patients with substance-related disorder and dysthymia had
received more substance-related disorder treatment in 18 of 20 measures.
Patients with substance-related disorder and dysthymia used 4.7 times more
substance-related disorder treatment dollars than patients with
substance-related disorder only, although their demographic characteristics were
similar. Past self-help activities and pharmacotherapy were remarkably similar
for both groups. Although substance-related disorder treatment differed
considerably between the two groups of patients, other types of psychiatric
treatment (i.e., non-substance-related treatment) did not differ between the two
groups. CONCLUSIONS: Patients with substance-related disorder and dysthymia are
referred to (or seek) substance-related disorder treatment more often than
patients with substance-related disorder only but are referred to (or seek)
non-substance-related psychiatric treatment no more often than patients with
substance-related disorder only. The cost of previous substance-related disorder
treatment was several times higher for the patients with substance-related
disorder and dysthymia.

Publication Types:
Multicenter Study

PMID: 9812117 [PubMed – indexed for MEDLINE]

47: J Psychiatry Neurosci. 1998 Nov;23(5):288-92.

Efficacy and tolerability of venlafaxine in the treatment of primary dysthymia.

Ravindran AV, Charbonneau Y, Zaharia MD, al-Zaid K, Wiens A, Anisman H.

Department of Psychiatry, University of Ottawa, Ont.

OBJECTIVE: Currently, there is no documentation of the efficacy of venlafaxine
(a serotonin norepinephrine reuptake inhibitor) in the treatment of dysthymia.
This open-label pilot investigation examined the efficacy and tolerability of
venlafaxine in patients with primary dysthymia without concomitant major
depression. METHODS: Fifteen patients were treated with venlafaxine for 12
weeks, with a dose range of 75 mg to 225 mg daily (taken orally), and symptom
changes were measured using standard instruments including the Hamilton
Depression Rating Scale (HAM-D). RESULTS: Significant changes from pretreatment
to posttreatment were observed (p < 0.001). Using the standard criteria of a 50%
reduction in HAM-D scores, 73.3% of patients were rated as responders. About
two-thirds of the patients reported adverse events, which were mostly mild and
brief in duration. CONCLUSION: Venlafaxine may be useful in the treatment of
primary dysthymia but placebo-controlled studies are required for confirmation.

Publication Types:
Clinical Trial

PMID: 9846033 [PubMed – indexed for MEDLINE]

48: J Affect Disord. 1998 Feb;48(1):47-56.

Amisulpride versus fluoxetine in patients with dysthymia or major depression in
partial remission: a double-blind, comparative study.

Smeraldi E.

Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric
Sciences, University of Milan-School of Medicine, Italy.

In a multicentre, double blind, parallel group study 281 patients with DSM III-R
diagnosis of dysthymia or a single episode of major depression in partial
remission were randomised to 3 months of treatment with amisulpride 50 mg/day or
fluoxetine 20 mg/day. The baseline Montgomery and Asberg Depression Rating Scale
(MADRS) total score was reduced by at least 50% in 74.1% of patients (103/139)
with amisulpride and 67.4% (87/129) with fluoxetine (P =0.230). No significant
differences between treatment groups were found in the reductions in mean total
score with the MADRS, Widlocher psychomotor retardation scale, Sheehan
disability scale, and CGI. Anxiety measured by HAM-A total mean score decreased
significantly more with amisulpride (63%) than with fluoxetine (54%; P = 0.021).
There were 13 dropouts due to adverse events with amisulpride and ten with
fluoxetine. The number of patients reporting at least one adverse event was
similar in the two groups (amisulpride 47.5%; fluoxetine 40.9%). As expected, in
the amisulpride group endocrine-like adverse events in female patients were the
most common, while nausea, dyspepsia, anorexia and insomnia occurred more
frequently with fluoxetine.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 9495601 [PubMed – indexed for MEDLINE]

49: J Affect Disord. 1998 Jan;47(1-3):169-75.

Does the chronological relationship between the onset of dysthymia and major
depression influence subsequent response to antidepressants?

Levitt AJ, Joffe RT, Sokolov ST.

Mood Disorders Program, Sunnybrook Health Sciences Centre, North York, Ontario,
Canada.

OBJECTIVE: To determine whether the chronological relationship between the onset
of dysthymia and the onset of the first major depression influences treatment
outcome in patients with double depression (DD). METHOD: Clinical and outcome
measures previously collected in 77 consecutive outpatients who presented with
major depression and who had pre-existing dysthymia (i.e. DD) were reviewed for
the current retrospective analysis. Subjects had been administered the Schedule
for Affective Disorders and Schizophrenia, Lifetime Version (SADS-LV), and the
Hamilton Rating Scale for Depression (HAM-D) prior to open antidepressant
treatment and after 5 and 12 weeks of therapy. Response was defined as a 50%
decline in HAM-D to score +/-8. Subjects were divided into those with the onset
of dysthymia before the first major depression (DysB; n = 47), onset of
dysthymia after major depression (DysA; n = 12) and those with onset of both
condition within 2 years of each other (INDIST; n = 18). RESULTS: There were no
significant differences between these three groups in baseline HAM-D. However,
DysA subjects had significantly higher mean HAM-D scores than the DysB subjects
at week 5 and the INDIST subjects at week 12. Response rates at week 12 were
lower in subjects with DysA (33%) as compared with DysB (57%; Fisher’s exact
test, P = 0.06) and INDIST (78%; Fisher’s Exact test P = 0.02). CONCLUSIONS:
These findings suggest that the onset of the first episode of dysthymia after
the first major depressive episode (i.e. DysA) may adversely affect response to
subsequent treatments in patients with DD.

Publication Types:
Clinical Trial

PMID: 9476757 [PubMed – indexed for MEDLINE]

50: J Clin Psychiatry. 1998;59 Suppl 10:13-5.

Geriatric dysthymia.

Kocsis JH.

Cornell Medical Center, New York Hospital, New York 10021, USA.

This article reviews what is known about the epidemiology, clinical
characteristics, and treatment of dysthymia in the geriatric age group. Although
less common in the elderly than in young adults, dysthymia may have its onset in
middle or late life. Geriatric dysthymia appears to have less associated
psychiatric comorbidity and closer links to severe life stresses, particularly
medical illnesses, than dysthymia with early-age onset. Preliminary reports of
response to antidepressant medications are encouraging in the elderly, but
randomized, placebo-controlled clinical trials are needed in samples of
dysthymic patients in this age group.

Publication Types:
Review

PMID: 9720477 [PubMed – indexed for MEDLINE]

51: Eur Neuropsychopharmacol. 1997 Oct;7 Suppl 3:S329-36.

Antidepressant efficacy in the treatment of dysthymia.

Invernizzi G, Mauri MC, Waintraub L.

Psychiatry Department 1, University of Milan, IRCCS Ospedale Maggiore di Milano,
Italy.

Although the existence of chronic depression has been recognized for a long
time, their definition was too inaccurate to enable reliable studies concerning
their treatment. Among the numerous diagnostic classes that patients with
chronic depression were assigned to, neurotic depression was the most common
one, and was often considered to be unresponsive to antidepressant medication.
Since DSM-III introduced ‘Dysthymic Disorder’, a new research was developed on
the efficacy of tricyclic antidepressants, MAOIs or new antidepressants, whose
results reversed previous opinion on its unresponsiveness. However the
interpretation of those studies are hampered by methodological problems, yet
unresolved, pertaining to the difficulty to differentiate dysthymia and major
depression, to the frequency of ‘double-depression’, the usual mildness of
symptoms in dysthymia, and the need of long-term trials.

Publication Types:
Review

PMID: 9405959 [PubMed – indexed for MEDLINE]

52: Int Clin Psychopharmacol. 1997 Jul;12(4):183-93.

Moclobemide and imipramine in chronic depression (dysthymia): an international
double-blind, placebo-controlled trial. International Collaborative Study Group.

Versiani M, Amrein R, Stabl M.

Federal University of Rio de Janeiro, Brazil.

An international, multicenter, placebo-controlled study was undertaken to
determine the safety and antidepressant efficacy of moclobemide, a new
reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of
dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly
assigned to an 8-week treatment in one of three groups (moclobemide, imipramine
and placebo). Patients were male or female outpatients aged between 18 and 65
years meeting DSM-III-R criteria for dysthymia, primary type, with late or early
onset. Of the patients in each group 85% completed the 8-week treatment period.
The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at
treatment endpoint was significantly higher in the moclobemide (60%) and
imipramine (49%) treatment groups than in the placebo group (22%). Differences
to placebo were also statistically significant both for moclobemide and for
imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for
Depression, final overall efficacy assessment, Clinical Global Impression and
symptom check list self-rating). A significant superiority of moclobemide and
imipramine over placebo was found in pure dysthymia and in double-depression, as
well as in early and late onset subgroups. In early onset cases, moclobemide was
significantly more effective than was imipramine on the Hamilton Rating Scale
for Depression. Anticholinergic symptoms and sleepiness were significantly more
frequent side effects on imipramine than on moclobemide or on placebo, and the
investigators’ final overall assessment of tolerability significantly favoured
moclobemide over imipramine. This study demonstrates the efficacy of high dose
moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against
placebo in the treatment of dysthymia. Moclobemide was better tolerated than was
imipramine.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 9347378 [PubMed – indexed for MEDLINE]

53: Br J Psychiatry. 1997 Apr;170:345-50.

Controlled efficacy study of fluoxetine in dysthymia.

Vanelle JM, Attar-Levy D, Poirier MF, Bouhassira M, Blin P, Olie JP.

Service Hospitalo-Universitaire de Sante Mentale et de Therapeutique, Centre
Hospitalier Sainte Anne, Paris, France.

BACKGROUND: There have been very few controlled studies of antidepressants in
dysthymia, particularly in samples diagnosed reliably and with an adequate
length of follow-up. In this investigation, we measured the long-term outcome in
a large group of patients meeting DSM-III-R criteria for dysthymia. This study
was designed to investigate whether fluoxetine is effective in the treatment of
dysthymia. METHOD: This randomised study including 140 patients, compared
fluoxetine (91 patients) and placebo (49 patients) on a double-blind basis in
two distinct phases: a short-term end-point (3 months with 20 mg/day fluoxetine)
and a medium-term end-point (6 months) where the initial responders continued
double-blind treatment unchanged and non-responders received an additional
treatment of 20 mg/day fluoxetine. RESULTS: After three months of treatment,
response was seen more frequently in the fluoxetine group (42/72) than in the
placebo group (14/39, P < 0.0001). Improved patients at 3 months were still
improved at 6 months. Furthermore, 50% of the nonresponders at 3 months improved
and rated as responders at 6 months, after fluoxetine was increased to 40 mg
daily. CONCLUSIONS: This study showed the significant and persistent action of
fluoxetine on dysthymia. The finding that 50% of the non-responders at 3 months
were improved at 6 months, after fluoxetine dosage was increased to 40 mg daily,
argues in favour of treating dysthymic patients for at least 6 months, and with
a higher dosage if the initial doses are ineffective.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 9246253 [PubMed – indexed for MEDLINE]

54: J Affect Disord. 1997 Apr;43(2):95-103.

Amisulpride versus imipramine and placebo in dysthymia and major depression.
Amisulpride Study Group.

Lecrubier Y, Boyer P, Turjanski S, Rein W.

Unite INSERM 302, Hopital Salpetriere, Paris, France.

Amisulpride, a selective antagonist of D2 and D3 dopamine receptors, acts
preferentially on presynaptic receptors increasing dopaminergic transmission at
low doses. In a multicentre, 6 months, placebo-controlled trial, amisulpride (50
mg/daily) was compared to imipramine (100 mg/daily) in the treatment of patients
with DSM-III-R criteria for primary dysthymia, dysthymia with major depression
or major depression in partial remission. A total of 219 patients were included.
Both analyses (intention-to-treat and “per protocol’ analysis) detected
significant differences between groups (active treatment vs. placebo) on all
main rating scales (CGI, MADRS, ERD, and SANS). The number of patients reporting
at least one adverse event was higher in the imipramine group than in the two
other, mainly due to anticholinergic effects. Endocrine symptoms were more
frequent in female patients treated with amisulpride. These results confirm the
interest of a drug acting on dopaminergic transmission such as amisulpride in
the treatment of depressed patients.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 9165379 [PubMed – indexed for MEDLINE]

55: Am J Psychiatry. 1997 Mar;154(3):390-5.

Double-blind comparison of sertraline, imipramine, and placebo in the treatment
of dysthymia: psychosocial outcomes.

Kocsis JH, Zisook S, Davidson J, Shelton R, Yonkers K, Hellerstein DJ, Rosenbaum
J, Halbreich U.

Department of Psychiatry, New York Hospital-Cornell Medical Center, NY, USA.

OBJECTIVE: The purpose of this study was to determine the effects of
antidepressant pharmacotherapy on mood symptoms and psychosocial outcomes in
dysthymia. METHOD: In a multicenter, double-blind, parallel-group trial, 416
patients with a diagnosis of early-onset primary dysthymia (DSM-III-R) of at
least 5 years’ duration without concurrent major depression were randomly
assigned to 12 weeks of acute-phase therapy with sertraline, imipramine, or
placebo. The psychosocial outcome measures used in the study were the Global
Assessment of Functioning Scale, the Social Adjustment Scale, the Longitudinal
Interval Follow-up Evaluation psychosocial ratings, and the Quality of Life
Enjoyment and Satisfaction Questionnaire. RESULTS: Sertraline and imipramine
were significantly better than placebo in improving psychosocial outcomes as
measured by the first three instruments. The Quality of Life Enjoyment and
Satisfaction Questionnaire scores demonstrated significant improvements from
baseline, and both active treatments produced significantly greater improvements
than placebo. Significantly fewer patients discontinued sertraline (6.0%) than
discontinued imipramine (18.4%) because of adverse events. CONCLUSIONS:
Pharmacotherapy is an effective treatment for dysthymia in terms of psychosocial
functioning as well as depressive symptoms, even when the dysthymia is
long-standing.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 9054788 [PubMed – indexed for MEDLINE]

56: J Clin Psychiatry. 1997 Feb;58(2):59-65.

The undertreatment of dysthymia.

Shelton RC, Davidson J, Yonkers KA, Koran L, Thase ME, Pearlstein T, Halbreich
U.

Division of Psychopharmacology, Vanderbilt University Medical Center, Nashville,
TN 37212-8646, USA.

BACKGROUND: Dysthymia is a chronic depressive condition that is quite prevalent.
This condition can exact a significant toll on the general health and quality of
life in the affected individual. Despite the frequency and consequences of
dysthymia, however, the condition is often not diagnosed or treated. We present
data on prior treatment from 410 patients with DSM-III-R dysthymia, primary
type, early onset without concurrent major depression. METHOD: Axis I and II
diagnoses were made by using the Structured Clinical Interviews for DSM-III-R,
Patient Version (SCID-P) and SCID II for Personality Disorders. The Hamilton
Rating Scale for Depression and the Clinical Global Impressions scale were also
completed. Prior treatment was assessed, with special attention paid to previous
antidepressant drug therapy and psychotherapy. RESULTS: Although the mean
duration of dysthymia was about 30 years and almost half of the patients had
previous episodes of major depression, only 41.3% had been treated with
antidepressants and 56.1% with psychotherapy. A past history of major depression
increased the frequency of prior antidepressant pharmacotherapy (45.7%) and
psychotherapy (59.4%) compared with no history of major depression (36.8% and
40.9%, respectively). Comorbid personality disorder increased the likelihood of
prior psychotherapy (70.7% vs. 49.6%) while having no effect on past
pharmacotherapy. A history of substance abuse did not affect the history of
antidepressant or psychotherapy treatment. In this study, dysthymia and
psychosocial outcomes improved with sertraline and imipramine treatment.
CONCLUSION: Dysthymic patients in this sample were significantly undertreated.
Newer antidepressant agents may alter the potential for pharmacotherapy
interventions in this vulnerable population.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 9062374 [PubMed – indexed for MEDLINE]

57: Psychopharmacol Bull. 1997;33(1):101-3.

A preliminary study on the efficacy of sertraline and imipramine on anger
attacks in atypical depression and dysthymia.

Fava M, Nierenberg AA, Quitkin FM, Zisook S, Pearlstein T, Stone A, Rosenbaum
JF.

Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114,
USA.

There is clinical and biological evidence suggesting that patients with anger
attacks, sudden spells of anger accompanied by intense autonomic activation, may
represent a distinct psychopathological subgroup of patients with depressive
disorders. We compared the prevalence of anger attacks in 168 outpatients with
atypical depression or primary dysthymia with 38 normal subjects and tested the
effect of treatment on anger attacks in a double-blind, placebo-controlled trial
of sertraline versus imipramine. Patients were randomly assigned to sertraline
(n = 56), imipramine (n = 52), or placebo (n = 60) and were administered the
Anger Attacks Questionnaire before and after treatment. Depressed outpatients
were significantly more likely to report anger attacks than controls. Anger
attacks ceased in 53 percent of the patients receiving sertraline, 57 percent of
those receiving imipramine, and 37 percent of those in the placebo group. Our
findings support previous studies indicating that anger attacks are more
prevalent among depressed outpatients than normals. Our results also suggest
that sertraline and imipramine may be more effective than placebo in reducing
the number of anger attacks following treatment although the differences were
not statistically significant. Larger studies are needed to confirm our
findings.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 9133758 [PubMed – indexed for MEDLINE]

58: Arch Gen Psychiatry. 1996 Sep;53(9):777-84.

Comment in:
Arch Gen Psychiatry. 1997 Oct;54(10):973.

A placebo-controlled, randomized clinical trial comparing sertraline and
imipramine for the treatment of dysthymia.

Thase ME, Fava M, Halbreich U, Kocsis JH, Koran L, Davidson J, Rosenbaum J,
Harrison W.

Department of Psychiatry, University of Pittsburgh School of Medicine, USA.

BACKGROUND: Despite the high prevalence of dysthymia and its associated
morbidity, few controlled trials have evaluated the efficacy of antidepressant
medication for this disorder. A 12-week, double-blind, placebo-controlled,
randomized, multicenter trial was performed to evaluate the safety and efficacy
of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia.
METHODS: A total of 416 outpatients (271 women and 145 men) aged 25 to 65 years
with DSM-III-R-defined, early-onset, primary dysthymia without concurrent major
depression were randomized to 12 weeks of treatment with sertraline, imipramine,
or placebo. RESULTS: Both active treatments resulted in significantly reduced
scores on the 17-item Hamilton Rating Scale for Depression (P = .04 and P = .01
for sertraline and imipramine vs placebo, respectively), the Montgomery-Asberg
Depression Rating Scale (P = .01 and P = .003 vs placebo, respectively), Hopkins
Symptom Checklist (P < .05), and the self-rated version of the Inventory of
Depressive Symptoms (P < .05). With the use of a Clinical Global impressions
improvement score of 1 or 2 (very much or much improved) to define response,
response rates were 59% for sertraline, 64% for imipramine, and 44% for placebo
(P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo). A
significantly greater proportion of patients receiving imipramine than those
receiving sertraline or placebo discontinued treatment because of adverse events
(P = .001 and P < .001, respectively). CONCLUSIONS: Pharmacotherapy provides
considerable relief from the symptoms of dysthymia in patients suffering from
this chronic affective disorder, with both sertraline and imipramine being more
effective than placebo. The greater tolerability of sertraline is an important
consideration because of the chronicity of dysthymia, which may require
prolonged treatment with antidepressant medication.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 8792754 [PubMed – indexed for MEDLINE]

59: J Clin Psychiatry. 1996 Jun;57(6):254-6.

Fluoxetine treatment of dysthymia in the elderly.

Nobler MS, Devanand DP, Kim MK, Fitzsimons LM, Singer TM, Turret N, Sackeim HA,
Roose SP.

Late Life Depression Clinic, New York, USA.

BACKGROUND: Despite their prevalence, little is known about the treatment of
mild depressive syndromes in older patients. The purpose of this study was to
evaluate the efficacy of fluoxetine in dysthymic disorder in the elderly.
METHOD: Twenty-three elderly outpatients with dysthymic disorder (DSM-III-R
criteria) entered a 13-week study of fluoxetine (2-week placebo run-in period
and 11 weeks of fluoxetine treatment with a dose range of 20-60 mg/day). Ratings
to assess clinical response included the Hamilton Rating Scale for Depression
(HAM-D), the Clinic Global Impression (CGI), and the Cornell Dysthymia Rating
Scale (CDRS). RESULTS: Nine patients (39%) had never received psychiatric
treatment during the index episode, despite a long duration of illness (mean +/-
SD = 18.5 +/- 17.1 years). Twenty of the 23 patients completed the entire study.
The mean +/- SD HAM-D (24-item) score decreased from 14.6 +/- 3.7 to 7.9 +/- 5.0
during the trial, and the CDRS score decreased from 28.1 +/- 9.1 to 15.7 +/-
10.0. When response criteria of a 50% reduction from baseline in the HAM-D
score, final HAM-D score < or = 8, and a CGI score of 1 or 2 (very much or much
improved) were used, 12 (60%) of the completers were responders. Side effects
were uncommon, and the fluoxetine was generally well tolerated. CONCLUSION:
These preliminary findings suggest that fluoxetine is an effective treatment in
elderly patients with dysthymic disorder. Double-blind, placebo-controlled
studies are warranted.

Publication Types:
Clinical Trial

PMID: 8666563 [PubMed – indexed for MEDLINE]

60: J Clin Psychopharmacol. 1995 Aug;15(4):280-3.

Predictors of response to desipramine in dysthymia.

Friedman RA, Parides M, Baff R, Moran M, Kocsis JH.

Department of Psychiatry, New York Hospital, Cornell Medical Center, Payne
Whitney Clinic, New York 10021, USA.

Little is known about factors that may predict the response of dysthymia or
other forms of chronic depression to treatment with antidepressant medication.
We investigated several sociodemographic and clinical variables for their
relationship to the acute treatment response to desipramine in subjects with
DSM-III-R dysthymia. Subjects with DSM-III-R dysthymia were treated with
desipramine in an open fashion for 10 weeks. Various clinical and
sociodemographic variables were assessed at baseline. Ratings of depressive
symptoms and severity and determination of categorical outcome were done during
treatment. Baseline extended family adjustment as measured by the Social
Adjustment Scale Self-Report was significantly better in the responders compared
with the nonresponders (2.1 +/- 0.5 vs. 2.6 +/- 0.8; t = 2.84, df = 52.11, p =
0.006). There was a trend (p = 0.06) for overall baseline social impairment
(SAS-SR) to be higher in nonresponders versus responders. Older age was a
significant predictor of higher depressive severity (Cornell Dysthymia Rating
Scale) and global impairment in the last week of the study. No other variable
significantly distinguished responders from non-responders. Although few of the
variables that were examined were found to affect acute treatment response,
better extended family adjustment as reported on the SAS-SR was a significant
predictor of good acute treatment response to desipramine in patients with
dysthymia.

Publication Types:
Clinical Trial

PMID: 7593711 [PubMed – indexed for MEDLINE]

61: Prog Neuropsychopharmacol Biol Psychiatry. 1995 Jul;19(4):637-53.

Stressful life events and coping styles in relation to dysthymia and major
depressive disorder: variations associated with alleviation of symptoms
following pharmacotherapy.

Ravindran AV, Griffiths J, Waddell C, Anisman H.

Royal Ottawa Hospital, University of Ottawa, Ontario, Canada.

1. Both major depression and dysthymia (chronic, low grade depression) were
associated with increased reports of minor stressors (daily hassles), and
feelings of loneliness, reduced uplifts, as well as the use of inappropriate
coping strategies (i.e., emotion-focussed rather than problem-oriented coping).
2. Although major depressive and dysthymic patients shared several features with
respect to symptomatology, dysthymics tended to report a greater number of
hassles than major depressives. 3. Treatment with serotonin reuptake inhibitors
over an 8-week period resulted in a marked alleviation of the depressive
symptoms in both patient groups, although the clinical effectiveness of the
drugs appeared somewhat later in dysthymics. 4. The attenuation of the
depressive symptoms was accompanied by a modest, but significant diminution in
reports of minor stressors, while the perception of uplifts remained unchanged.
Moreover, recovery from depression was associated with changes in coping style,
such that patients relied less on inappropriate emotion-focussed coping
strategies.

Publication Types:
Clinical Trial

PMID: 8588062 [PubMed – indexed for MEDLINE]

no