Dysthymic Disorder: The Persistent Depression PSYCHIATRY BOARD REVIEW MANUAL STATEMENT OF

®
PSYCHIATRY BOARD REVIEW MANUAL
STATEMENT OF
EDITORIAL PURPOSE
The Hospital Physician Psychiatry Board Review
Manual is a study guide for residents and
practicing physicians preparing for board
examinations in psychiatry. Each quarterly
manual reviews a topic essential to the current practice of psychiatry.
PUBLISHING STAFF
PRESIDENT, GROUP PUBLISHER
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EDITORIAL DIRECTOR
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ASSOCIATE EDITOR
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EDITORIAL ASSISTANT
Farrawh Charles
EXECUTIVE VICE PRESIDENT
Barbara T. White
Dysthymic Disorder: The
Persistent Depression
Series Editor:
Jerald Kay, MD
Professor and Chair, Department of Psychiatry, Wright State
University School of Medicine, Dayton, OH
Contributors:
Randy A. Sansone, MD
Professor, Departments of Psychiatry and Internal Medicine, Wright
State University School of Medicine, Dayton, OH; Director of
Psychiatry Education, Kettering Medical Center, Kettering, OH
Terry Correll, DO
Assistant Professor, Department of Psychiatry, Wright State University
School of Medicine; Attending Psychiatrist, Twin Valley Behavioral
Healthcare, Dayton, OH
EXECUTIVE DIRECTOR
OF OPERATIONS
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Table of Contents
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Endorsed by the
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Medical Education
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Historical Perspectives . . . . . . . . . . . . . . . . . . . . . . . 3
Comorbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Outcome and Prognosis . . . . . . . . . . . . . . . . . . . . . . 8
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Cover Illustration by Kathryn K. Johnson
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Psychiatry Volume 9, Part 4 1
PSYCHIATRY BOARD REVIEW MANUAL
Dysthymic Disorder:
The Persistent Depression
Randy A. Sansone, MD, and Terry Correll, DO
INTRODUCTION
Dysthymic disorder (DD) is a form of chronic depression that affects up to 6% of the general population and
5% to 15% of primary care populations. While the explicit etiology remains unknown, a variety of factors appear to
contribute to this type of depression. DD is characterized
by an insidious onset; waxing and waning symptomatology of at least 2 years’ duration in adults and 1 year in children and adolescents; brief periods of euthymia; and
symptoms that typically cluster around cognitive, social,
and motivational areas. This form of depression is frequently comorbid with other medical and psychiatric disorders. Nearly all antidepressant trials have shown that
patients benefit from these agents in varying degrees, and
other forms of therapy are being investigated. However,
the long-term outcome for sufferers of this disorder
remains unclear.
EPIDEMIOLOGY
GENERAL POPULATION
The community prevalence of dysthymia in the
United States varies depending on the source of the
data. For example, according to data collected by the
National Institute of Mental Health (1988)1 for the
Epidemiological Catchment Area Study, the lifetime
prevalence of DD in the general population is 3.1%.
Kessler and colleagues,2 who reported on data from the
National Comorbidity Survey in 1994, found the lifetime prevalence to be 4.8% among men and 8% among
women (average, 6.4%). These latter findings echo the
gender patterns typically observed in mood and anxiety
disorders. Collectively, the data from these 2 large studies suggest that the lifetime prevalence of DD in the
general population is approximately 3% to 6%. Narrow
and colleagues3 reanalyzed these data and determined
that the 1-year prevalence rate for dysthymia in the general population is 1.6%.
2 Hospital Physician Board Review Manual
In addition to general population studies, nonclinical
subpopulations have been examined. Among U.S. adolescents, the 1-year prevalence of dysthymia in a study by
Garrison and colleagues4 was 3.4%. In a study examining Chinese Americans, Takeuchi and colleagues5 determined the lifetime prevalence of dysthymia as 5.2%.
These rates are comparable with those reported for the
broader population.
Do U.S. prevalence rates for dysthymia in the general population reflect international findings as well? The
available studies are sparse. In a Norwegian study,6 the
lifetime prevalence of dysthymia in the community was
5.9% among men and 13.3% among women (average,
10%). In a Swedish sample of very elderly individuals
(aged 78–100 years), Forsell and colleagues7 found a
current or point prevalence rate of 3.5%.
PRIMARY CARE POPULATION
According to Howland,8 the prevalence of dysthymia
in U.S. primary care samples ranges from 1.3% to
31.9% (pooled prevalence rate of 7%). Spitzer and colleagues9 report that the majority of studies suggest that
5% to 15% of primary care patients suffer from DD. In
addition, comparable rates have been found among
low-income Mexican Americans in primary care settings.10
In an international study of primary care patients,
Lecrubier and Weiller11 examined the prevalence of dysthymia among 25,916 patients from 14 countries; the
current or point prevalence rate was 2.1%. In a Canadian study, Browne and colleagues12 reported the
12-month prevalence of DD as 3.9% for men and 5.9%
for women. In a Spanish sample, Ruiz-Doblado13 determined a current or point prevalence of approximately
0.5%. Baldwin14 summarized the international data and
concluded that the point and lifetime prevalence rates
for dysthymia were between 1.2% to 3.7% and 0.5% to
20.6%, respectively.
In mental health settings, Klein and colleagues15 and
Markowitz and colleagues16 examined psychiatric outpatients for dysthymia and found prevalence rates of
22% and 36%, respectively.
Dysthymic Disorder: The Persistent Depression
SUMMARY
In the U.S. general population, the lifetime prevalence
rate for dysthymia appears to be approximately 3% to 6%.
The prevalence of dysthymia in U.S. primary care settings
is higher than in the general population (5%–15%) and
even higher in mental health settings (one quarter to one
third of patients). The data from international general
and primary care populations appear too limited to draw
meaningful conclusions. When gender has been studied,
the majority of investigations indicate higher prevalence
rates in females compared with males.
ETIOLOGY
As with most psychiatric disorders, the explicit etiology of DD is unknown. It is likely that there are multiple contributory factors that may act alone or in concert
to precipitate the symptoms of DD.
BIOLOGICAL ABNORMALITIES
Sleep abnormalities, often encountered in major depressive disorder (MDD), are found in 25% to 50% of
adults with DD (eg, reduced rapid eye movement latency but increased density, reduced slow-wave sleep,
impaired sleep continuity).17 Dysthymic individuals with
polysomnographic abnormalities are more likely to
have family histories of MDD and may respond better to
antidepressants.17
DD has been associated with elevated production of
interleukin-1 in mitogen-stimulated lymphocytes18 and
possible serotonergic dysfunction.19,20 Compared with
males, platelet monoamine oxidase activity may be significantly lower in female patients with DD.21 Dexamethasone nonsuppression is uncommon in DD unless MDD
also is present.17 Total testosterone levels may be lower in
elderly men with DD compared with younger men with
MDD and men without depressive symptoms. This suggests the possibility of hypothalamic-pituitary-gonadal
axis hypofunction as a contributory factor in DD.22
FAMILY STUDIES
DD is more common among the first-degree biological relatives of individuals with MDD.23 In addition,
DD, MDD, and personality disordersare more common
in the first-degree relatives of individuals with DD.17
DIAGNOSIS
DD is characterized by a chronic, smoldering, lowgrade dysphoric mood that lasts at least 1 year in children
or adolescents or 2 or more years in adults (DSM-IV-TR
Criterion A). During periods of depressed mood, at least
2 of the following additional symptoms are present: poor
appetite or overeating, insomnia or hypersomnia, low
energy or fatigue, low self-esteem, poor concentration or
difficulty making decisions, and feelings of hopelessness
(Criterion B). The depressive symptoms of DD tend to
be cognitive (eg, low self-esteem, pessimism, feelings of
inadequacy) rather than vegetative (eg, insomnia, loss of
appetite).24 These symptoms often are accompanied by
social withdrawal and low motivation.
According to the results of the DSM-IV mood disorders
field trial,24 psychotic features are rare; there is no evidence of manic, mixed, or hypomanic episodes; and the
dysphoria may be punctuated by brief periods of
euthymia (up to 2 months per year). In children and adolescents, symptoms may include pessimism, low selfesteem, poor social skills, and irritability or crankiness.17
The essential defining feature of DD is the chronicity of
depressive symptoms as well as significant morbidity. Impairment may occur in nearly all areas of life functioning.
Because of the longstanding duration of symptoms, some
individuals may misinterpret that “this is just how I am.”
DSM-IV-TR adds the following specifiers for DD:
(1) early onset, for symptom onset before age 21 years;
(2) late onset, for symptom onset at 21 years or older;
and (3) with atypical features, if the symptom pattern
includes mood reactivity and 2 other atypical symptoms
(ie, weight gain or increased appetite, hypersomnia, leaden paralysis, interpersonal rejection sensitivity). The specifier of early-onset DD is especially important because of
its association with particularly high rates of recurrence,
subsequent episodes of MDD, comorbid personality disorders, psychiatric hospitalizations, and among women,
low educational achievement, which may lead to underemployment and reduced income.25 Atypical features are
more common in women and are associated with an earlier age of onset and more chronic course with only partial interepisode recovery.17
HISTORICAL PERSPECTIVES
The term “dysthymia” was originally coined by Flemming in 1844.26 However, in the late 1880s, Kahlbaum
was the first to develop a modern description of the disorder as a chronic, low-grade depression.27 In 1921,
Kraeplin28 described “depressive temperament,” which
he characterized as “a permanent, gloomy, emotional
stress in all areas of life… they do not find complete, lasting satisfaction in their work, as they keep in view the
mistakes and deficiencies of their achievements, as well
Psychiatry Volume 9, Part 4 3
Dysthymic Disorder: The Persistent Depression
Table 1. DSM-IV-TR Alternative Research Criterion B
for Dysthymic Disorder
Table 2. DSM-IV-TR Criteria for Depressive
Personality Disorder
B. Presence, while depressed, of 3 (or more) of the following:
A pervasive pattern of depressive cognitions and behaviors
beginning by early adulthood and present in a variety of
contexts, as indicated by 5 (or more) of the following:
Low self-esteem or self-confidence, or feelings of inadequacy
Feelings of pessimism, despair, or hopelessness
Generalized loss of interest or pleasure
Social withdrawal
Chronic fatigue or tiredness
Feelings of guilt, brooding about the past
Subjective feelings of irritability or excessive anger
Decreased activity, effectiveness, or productivity
Difficulty in thinking, reflected by poor concentration,
poor memory, or indecisiveness
Adapted with permission from American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed., text revision.
Washington (DC): American Psychiatric Association; 2000:775.
as approaching difficulties, rather than the value of the
thing accomplished.”
Prior to the publication of the DSM-III29 in 1980,
many clinicians conceptualized longstanding depression as characterologic in nature (eg, depressive neurosis and depressive personality disorder) and recommended long-term psychotherapy as the primary
treatment. However, since the redefinition of chronic
depression as an Axis I affective disorder, pharmacologic and psychotherapeutic research has been stimulated to improve the treatment of patients with DD. As
an interesting compromise between the Axis I and II
perspectives, Widiger30 maintains that DD should be
viewed as a hybrid disorder, spanning the border between mood and personality disorders.
Diagnostic reorganization continues to underscore
the heterogeneity of DD and all depressive disorders.
With ongoing controversy concerning which criteria
best define DD, DSM-IV-TR includes alternative criteria
for DD as well as proposed diagnostic criteria for
depressive personality disorder (Tables 1 and 2).17
It may be that the depressive disorders exist on a continuum with depressive personality disorder representing the early-onset variant. Other depressive disorders,
which likely fall within the continuum, may include the
criteria sets and axes for further study that are listed in
appendix B of the DSM-IV-TR (eg, minor depressive
disorder, recurrent brief depressive disorder, mixed
anxiety-depressive disorder, postpsychotic depressive
disorder, premenstrual dysphoric disorder). These diagnoses currently would be categorized in DSM-IV-TR as
4 Hospital Physician Board Review Manual
Usual mood is dominated by dejection, gloominess,
cheerlessness, joylessness, unhappiness
Self-concept centers around beliefs of inadequacy,
worthlessness, and low self-esteem
Critical, blaming, and derogatory toward self
Brooding and given to worry
Negativistic, critical, and judgmental toward others
Prone to feeling guilty or remorseful
Does not occur exclusively during major depressive
episodes and is not better accounted for by dysthymic
disorder
Adapted with permission from American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed., text revision.
Washington (DC): American Psychiatric Association; 2000:789.
depressive disorder not otherwise specified. Obviously,
additional trials and evidence are needed to further clarify the boundaries of these mood disorders.
DYSTHYMIA VERSUS MAJOR DEPRESSION: THE CURRENT
STATUS
Given the historical evolution of dysthymia and
major depression, the current differences are presented
in Table 3. In MDD, there is a fairly well defined onset
of symptoms compared with the typical insidious onset of
symptoms in DD. MDD tends to manifest as discrete
episodes, while DD has a more chronic and enduring
course. MDD tends to be more symptomatically intense
compared with the discreet cognitive, social, and motivational symptoms associated with DD. While the symptoms
in MDD are sustained, DD may be interrupted by brief
euthymic periods (< 2 months). Response to treatment is
“good to excellent” in MDD, but only “fair” or incomplete
in DD with two thirds of patients remaining symptomatic
after 1 decade.31 Essentially, the clinical texture of these
2 types of depression is quite different and will undoubtedly evolve with future generations of DSM revisions.
COMORBIDITY
“Pure” dysthymia, or dysthymia without any comorbid psychiatric or medical condition, is relatively rare.
Indeed, it is so uncommon that the investigators participating in the National Institute of Mental Health
Dysthymic Disorder: The Persistent Depression
Table 3. Dysthymia versus Major Depression
Clinical Characteristic
Major Depression
Dysthymia
Onset
Well defined
Insidious
Criteria of symptom duration
2 weeks
2 years
Texture of symptoms
Intense, sustained symptoms
Smoldering, waxing and waning symptoms
with brief periods of euthymia
Symptom constellation
Often psychomotor, appetite/weight and
sleep changes
Often cognitive, motivational, social symptoms
Treatment response
Good to excellent
Fair, modest, high relapse rate
Collaborative Study on the Psychobiology of Depression had difficulty recruiting “pure” dysthymic subjects
and had to change their methodology to acquire participants.32 Given the high level of comorbidity, the
identification of these comorbid conditions may be
clinically helpful in developing a course of treatment.
COMORBID PSYCHIATRIC DISORDERS
MDD
MDD is the most common comorbid Axis I disorder
in those with DD. DD itself may be viewed as a risk factor for MDD; in clinical settings, up to 75% of individuals with DD develop MDD within 5 years.17 When MDD
occurs in the course of DD, it is termed double depression, and the clinical course is characterized by high levels of depressive symptomatology, poor social adjustment, and global psychopathology.32,33
Anxiety Disorders
Anxiety disorders are comorbid in approximately
50% of persons with DD.34 In a large series of primary
care patients with DD, 90% screened positive for other
Axis I disorders, which in addition to MDD included
panic disorder, simple phobia, and generalized anxiety
disorder.35 Up to 15% of dysthymic patients also have
comorbid social phobia.36
Personality Disorders
When comparing Axis II comorbidity between acute
versus chronic depressives, chronic depressives demonstrate a higher prevalence,37 especially among those with
early-onset DD (ie, 20%–40% higher).37–39 Associated
personality disorders may include avoidant, dependent,
self-defeating, histrionic, narcissistic, and borderline personality disorders.17,40,41 The presence of a personality disorder is related to more severe overall psychopathology.37
Somatoform Disorders
Patients with somatoform disorders, such as somati-
zation and hypochondriasis, have an increased rate of
DD (2.8%–45.2%),42 – 46 underscoring the importance
of depressive screening in this population.
Substance Abuse
As with all psychiatric disorders, substance abuse is
often comorbid with DD. Since alcohol is one of the
most potent depressive agents, it is imperative to routinely screen for substance abuse/dependence and
appropriately address these issues.
COMORBID MEDICAL DISORDERS
Studies consistently indicate that dysthymia is significantly associated with poor health8 and that sufferers
are likely to use 1.5 to 2 times as many medical services
as nondepressed patients, even after controlling for
chronic medical illness.25 Common co-occurring medical illnesses include neurologic conditions (eg, Parkinson’s disease, cerebrovascular disorders, multiple
sclerosis, migraine headaches, and pain syndromes),
sleep disorders, chronic fatigue, hypothyroidism,8
rheumatoid arthritis,47 and AIDS.48 Not all medical illnesses demonstrate this association, as indicated by the
low rate of DD among cancer patients.8
COMORBIDITY IN CHILDREN AND ADOLESCENTS
In children, DD may be associated with attentiondeficit/hyperactivity disorder, conduct disorder, anxiety
disorders, learning disorders, and mental retardation.17
Childhood and adolescent DD also is associated with a
substantial risk for the later occurrence of both recurrent MDD and bipolar disorder.
COMORBIDITY IN THE ELDERLY
Midlife onset of DD appears to have less psychiatric
comorbidity and more relationship to life stressors, particularly medical illnesses.49–51 These factors suggest a better overall prognosis. About one third of elderly dysthymic
patients have personality disorders, with obsessive-
Psychiatry Volume 9, Part 4 5
Dysthymic Disorder: The Persistent Depression
compulsive personality disorder being the most common,
followed by avoidant personality disorder.52
TREATMENT
PHARMACOTHERAPY
Antidepressant Monotherapy
A multitude of studies have been undertaken to assess
the efficacy of antidepressants in the treatment of DD
(Table 4). A number of studies are double-blind or
placebo-controlled, and nearly an equal number are
open label. The majority of these studies include less
than 50 subjects per study. While not evident in Table 4,
the duration of trials varies from study to study, with few
beyond 12 weeks. All of the studies indicate that many if
not most patients respond to some degree to antidepressant treatment. This conclusion is supported by numerous authors.53–56 While only 1 study of monoamine oxidase inhibitors (MAOIs) is noted in Table 4, several
authors affirm their efficacy in dysthymia as well.57–60 In
addition, in their review of the available randomized controlled drug trials for the treatment of dysthymia (n = 15
and 16, respectively), Lima and Moncrieff61 and de Lima
and Hotopf62 conclude that the efficacy among the different groups of antidepressant drugs is similar.
Despite the potential effectiveness of antidepressant
therapy in the treatment of dysthymia, there is controversy about the genuine robustness of responses with
medications. In this regard, Howland63 acknowledges
that the antidepressant response in DD is typically less
robust than that found in major depression. Fawcett55
confirms that while most studies affirm improvement,
scores on rating scales indicate that at the end of treatment trials, many patients experience only a partial
response and fail to achieve a full remission. Therefore,
while antidepressant medication is clearly helpful,
many patients do not experience full remission. The
genuine extent of these modest or partial responses to
antidepressants among dysthymic patients is unknown.
As for an antidepressant strategy, treatment algorithms
are available.64,65 Regardless, the initial use of selective
serotonin reuptake inhibitors (SSRIs) can be justified
based upon their broad clinical efficacy with a variety of
symptoms or disorders other than depression including
anxiety, social phobia, panic attacks, impulsivity, worry,
posttraumatic stress, obsessive-compulsive disorder,
bulimia nervosa, and premenstrual dysphoric disorder.66
This seemingly unique feature of SSRIs may be particularly useful given the observation that DD is highly comorbid with other psychiatric disorders. However, this ratio-
6 Hospital Physician Board Review Manual
nale does not preclude the use of other antidepressants as
initial treatment choices. In addition, side effect profiles
and patient characteristics are relevant factors in initial
drug selection.
Should an initial antidepressant trial be unsuccessful,
changing to an antidepressant with a different mode of
neurotransmitter activity appears logical.67 Indeed, Thase
and colleagues68 found that nonresponders who were
switched from sertraline to imipramine, or vice versa,
experienced a clinical improvement 50% of the time.
Because dysthymia is a chronic form of depression,
patients may require longer drug-evaluation trials than
those observed in major depression.27,69 Kocsis70 indicates
that a substantial number of patients experience initial
partial remission but with time report greater remission,
reinforcing the concept of longer drug-evaluation trials.
Twelve-week trials are recommended.64,71 Because few
patients have robust responses with antidepressant
monotherapy, it may be difficult to determine what is an
acceptable response at the 12-week juncture.
In addition to the preceding guides, various authors
have broached management suggestions in the pharmacotherapy of dysthymia. In this regard, Dunner72 emphasizes the importance of higher doses of medication and
longer treatment than that required for major depression. Frances73 acknowledges the risk of patient sensitivity to side effects, implying the need to be cautious with
dose increases. This is a particular concern among dysthymic patients with Axis II comorbidity and/or earlyonset dysthymia. Kornstein and colleagues74 suggest that
women may be more likely to respond to SSRIs and men
to tricyclic antidepressants. Finally, Baldwin14 recommends that antidepressant therapy be undertaken in
conjunction with psychological therapies.
Augmentation Strategies
Kocsis70 underscores that fewer than 50% of patients
achieve a full remission with a single agent. Should prescribers initiate a change in antidepressants? According to
Posternak and Zimmerman,75 switching antidepressants
may be somewhat less effective than an augmentation
strategy. This suggests that combinations of medications
be considered, although a well-defined, empirically determined strategy remains elusive. Note that many of the augmentation strategies discussed in the empirical literature
refer to refractory depression but also may be used in the
treatment of dysthymia.
Medications used for the augmentation of treatmentresistant depression include lithium;76,77 psychostimulants such as methylphenidate,78 dextroamphetamine,78
and modafinil;79,80 gabapentin;81,82 buspirone;83–86 and
pindolol.87 Several studies also indicate that thyroxine88,89
Dysthymic Disorder: The Persistent Depression
Table 4. Published United States Studies of Antidepressants in the Treatment of Dysthymia or Chronic
Depression
Drug Class
First Author
Year
N*
MAOIs
Moclobemide
de Mello
2001
35
Stewart
Marin
Friedman
Kocsis
Kocsis
Bakish
Salzmann
Thase
Versiani
Kocsis
1985
1994
1995
1996
1988
1994
1995
1996
1997
1997
16
75
12
129
22
16
34
91
103
136
Zanalda
Dunner
Rosenthal
Hellerstein
Bakish
Ravindran
Nobler
Vanelle
Waslick
de Jonghe
Rabe-Jablonska
Ballus
Nobile
Rocca
Rocca
1998
2002
1992
1993
1994
1994
1996
1997
1999
1991
2000
2000
2000
2002
2002
20
15
12
16
34
52
23
91
19
26
21
43
7
28
32
Thase
Chinchilla
Ravindran
Amore
Nixon
Kocsis
1996
1997
2000
2001
2001
1997
113
50
158
150
8
134
Dunner
Dursun
Rosenthal
Hellerstein
1999
2002
1992
2001
15
6
8
21
TCAs
Desipramine
Imipramine
SSRIs
Citalopram
Fluoxetine
Fluvoxamine
Paroxetine
Paroxetine +
Amisulpride
Sertraline
Other
Mirtazepine
Nefazodone
Trazodone
Bupropion
Study Description
Findings
Randomized
Significant improvement
DB, PC
Open label
Open label, retreatment
Open label, placebo phase
DB, PC
DB, PC
DB, PC
DB, PC
DB, PC
DB, PC
Desipramine = placebo
70% response
92% full remission
Desipramine > placebo
Impramine > placebo
Impramine > placebo
Impramine > placebo
Impramine > placebo
Imipramine > placebo
64% response
Open label
Open label
Open label, randomized
DB, PC
Open label
Open label
Placebo run-in
DB, PC
Open label, children
DB, randomized
Randomized
Open label, age < 18
Open label, randomized
Open label, randomized
Improvement
Majority responded
71% response average
62.5%, fluoxetine > placebo
Symptom reduction
73% response, > in females
60% response
Fluoxetine > placebo
73% response
Modest improvement
56% response
29% response
71% response
54% response
56% response
DB, PC
Open label
DB, PC
DB
Open label
DB, PC
Sertraline > placebo
Improvement
33%–47% improved scores
69% response
67% response
59% response
Open label
Pilot study
Open label, randomized
Open label
Effective
Improvement
71% response average
71% response, < with substance abuse
NOTE: For studies comparing 2 drugs, individual drugs are listed. This contains the majority of pharmacologic studies for the treatment of dysthymia and chronic depression; however, studies beyond PsycINFO, MEDLINE, or those reported at meetings may not be included. (DB = double-blind; MAOI = monoamine oxidase inhibitor; PC = placebo-controlled; SSRI = selective serotonin reuptake inhibiter; TCA = tricyclic antidepressant.)
*Number of subjects on active drug.
Psychiatry Volume 9, Part 4 7
Dysthymic Disorder: The Persistent Depression
and triiodothyronine90 augmentation may improve depressive symptoms. Indeed, one group of French investigators91 routinely supplements thyroid hormones in
patients who are in the upper 25th percentile of normal
thyroid-stimulating hormone range to achieve an antidepressant response.
The use of low-dose, atypical antipsychotic medications is another consideration. The effectiveness of olanzapine92,93 and risperidone92 is noted in the literature. This
does not exclude the possibility of using other atypical
antipsychotic drugs, and there are few comparison trials.92
Combining antidepressants is another possible option. Lam and colleagues94 reviewed 27 studies (n =
667) of combined antidepressant treatment and concluded that the overall response rate for this type of augmentation was 62.2%. However, the risks of particular
antidepressant combinations (eg, MAOIs and other
antidepressants, bupropion and antidepressants that
may inhibit its metabolism through the 2B6 isoenzyme,
SSRIs and tricyclic antidepressants) have not been well
elucidated.
Finally, some studies suggest mood benefits with the
addition of vitamins or other naturally occurring substances. Examples include folate,95,96 chromium,97 and
omega-3 fatty acids (but not docosahexaenoic acid).98–100
At the present time, no empirically confirmed strategy for augmentation is known.101 We suggest weighing
the potential benefits and risks in individual patients
and attempting lower-risk interventions at the outset.
For healthier outpatients, these may include the addition of folate, eicosapentaenoic acid, buspirone,
gabapentin, and low-dose atypical antipsychotics, with
subsequent consideration of dual antidepressants, lithium, and other anticonvulsants.
NONPHARMACOLOGIC INTERVENTIONS
In addition to medications, nonpharmacologic
interventions have been utilized in the treatment of dysthymia including cognitive behavioral treatment,102 – 105
interpersonal therapy,106 – 108 manualized group therapy,109 problem-solving therapy,110 and exercise.111 While
it is not entirely clear if there are any specific advantages to one intervention over another, or whether specific subpopulations of patients are more likely to respond to one treatment over another, cognitive
approaches have been the most frequently studied112
and appear promising.
As a caveat, few empirical data exist on the combination strategy of medication and nonpharmacologic
intervention. In a study of chronic major depression,
Keller and colleagues113 found that in comparison with
either treatment, the combination of drug treatment
8 Hospital Physician Board Review Manual
(in this case, nefazodone) and a version of cognitive
therapy offered the maximum benefit to patients.
Whether these findings might apply to dysthymic
patients remains unknown. However, other authors
support combination therapy in the treatment of dysthymia.72,114
OUTCOME AND PROGNOSIS
Long-term outcome studies (ie, those longer than
12 months) among dysthymic patients are scarce
(Table 5). In addition, these studies are difficult to interpret because of the various measures used for recovery,
as well as the different types of study populations (eg, private practice, elderly). However, one theme emerges
from this overview—a substantial number of sufferers do
not experience a sustained recovery. Indeed, even
among those who experience remission, there is a reasonable risk of relapse. We are not aware of any empirical evidence that suggests that dysthymic symptoms
diminish or burn out with age. Collectively, these findings suggest that, for many individuals, dysthymia will be
a chronic and perhaps lifelong disorder that undergoes
exacerbations and remissions throughout the life cycle.
Specific variables may affect the course of the disorder.
One study examined the role of life stressors among those
diagnosed with DD and investigators concluded that life
events, particularly new-onset stressors or the combination of new-onset and chronic stressors, play a meaningful role in precipitating major depressive episodes.115 In
addition, early-onset dysthymia may be a marker for recurrent affective disorders in adulthood.116 Almost all patients with dysthymia eventually experience major depressive episodes.117 The relationship between the onset of
dysthymia and major depression also may have an influence on prognosis. The onset of the first episode of dysthymia after a major depression, rather than before or
concurrently, may indicate a more adverse course.118
As for prognostic indicators, early-onset dysthymia
appears to be associated with a less favorable outcome
and may require a longer recovery time.116 This is in
line with our clinical experience, which suggests that
early-onset dysthymia is more difficult to treat and less
likely to have robust responses to treatment, compared
with late-onset dysthymia. Indeed, those with late-onset
dysthymia and a good premorbid psychiatric adjustment may fare very well.
As for other prognostic indicators, demographic and
other clinical variables are not strong predictors of outcome.119 However, according to Durban and colleagues,119 negative predictors may include a childhood
Dysthymic Disorder: The Persistent Depression
Table 5. Outcome Studies in Dysthymia with More Than 1-Year Follow-up
First Author
Year
n
Study Description
Findings
Kivela
1993
199
5-year, naturalistic follow-up of elderly sample (aged 60–94)
29% males, 39% females recovered
Oldehinkel
1999
061
20-month follow-up of community sample of
adolescents
33% remission
Haykal
1999
042
5-year follow-up of psychiatric outpatients
on fluoxetine
Sustained response rate of 76% with
antidepressants
Klein
2000
086
5-year, naturalistic follow-up of early-onset,
dysthymic psychiatric outpatients
Recovery rate = 52.3%; among recoveries, 45.2% relapse
history of sexual abuse, poor relationships with both
parents, and family histories of drug abuse and/or
Cluster A personality disorders. According to Hayden
and Klein,120 comorbid anxiety disorders, Cluster C personality features, chronic stress, and eating disorders
also may be associated with lower rates of recovery and
higher levels of depression at follow-up.
4.
5.
6.
SUMMARY
7.
DD is a common form of depressive illness. While
the explicit etiology remains unknown, the diagnosis is
dependent upon a minimal 2-year duration and a
symptom presentation that may appear quite different
than major depression. The disorder is highly comorbid with other psychiatric and medical disorders, particularly major depression. In the approach to treatment, antidepressant monotherapy is the initial
approach, but the clinician should anticipate the need
for combination medications (ie, augmentation strategies). There is no consensus regarding an augmentation algorithm. The outcome of dysthymia remains
somewhat controversial. While most patients experience clinical improvement with treatment, unfortunately many may not fully recover and relapses and
recurrences may be the rule rather than the exception.
14.
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