Dysthymic Disorder and Other Chronic Depressions

Mario A. Cristancho, M.D.
James H. Kocsis, M.D.
Michael E. Thase, M.D.
Dysthymic Disorder
and Other Chronic
Depressions
Abstract: Chronic forms of depression have been closely studied over the last three decades, and it is now widely
recognized that these conditions are better classified under the umbrella of affective disorders rather than characterological or personality disorders. Chronic depressive disorders include dysthymic disorder, chronic major depressive
episode, major depressive episode superimposed on dysthymic disorder (double depression), as well as recurrent major
depressive disorder without full interepisode recovery. Chronic forms of depression are prevalent in the general
population, and even those with low grade severity can lead to significant functional impairment, occupational dysfunction, suicide attempts, and worse prognosis. Given the obvious potential for deleterious effects, chronic forms of
depression should be promptly recognized and aggressively treated. Clinical benefit from using psychopharmacologic
agents alone or in combination with psychotherapy for the treatment of chronic depression has been demonstrated. In
this article the authors review pertinent clinical and diagnostic aspects in chronic depressive disorders as well as their
treatment.
Chronic forms of depression were once understood
as mainly a characterological or personality disorder
(1). However, as these depressive states have been
more closely studied over the last three decades, it
has been more widely recognized that these conditions are better classified along with the other
affective disorders. Chronic depressive disorders include dysthymic disorder, chronic major depressive
episode, major depressive episode superimposed on
dysthymic disorder (double depression), as well as
recurrent major depressive disorder without full
interepisode recovery. These subforms of chronic
depression are included in DSM-IV either as speci-
fiers or as independent diagnostic category (e.g.,
dysthymic disorder). However, a broader category
called “chronic depression” is being proposed for
DSM-5, with the intent to encompass all forms of
longstanding depression other than a chronic major
depressive episode (2).
The majority of the available information on this
subject derives from studies on dysthymic disorder,
which is the most frequently studied entity among
the various forms of chronic depression. However,
when possible, specific clinical and epidemiologic
characteristic for each subform of chronic depression will be highlights throughout the manuscript.
DIAGNOSIS
Author Information and CME Disclosure
Mario A. Cristancho, M.D., Department of Psychiatry, University of Pennsylvania, Philadelphia, PA.
James H. Kocsis, M.D., Department of Psychiatry, Weill Medical College, New York, NY.
Michael E. Thase, M.D., Department of Psychiatry, University of Pennsylvania, Philadelphia, PA.
All authors report no competing interests.
Dr. Cristancho is supported through the NIMH-funded Clinical Research Scholars Program of the
Department of Psychiatry, University of Pennsylvania.
Address correspondence to: Mario A. Cristancho, M.D., 3535 Market St.–4th floor, Philadelphia, PA
19104; e-mail: [email protected]
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An individual with a longstanding, low-grade
depression (i.e., dysthymia) has been classically portrayed as habitually gloomy, introverted, brooding,
overly conscientious, incapable of fun, and preoccupied with personal inadequacy and failure (3).
The concept of dysthymia has gone through different stages of development and was officially included as an axis I condition in DSM-III, essentially
replacing the DSM-II diagnosis of neurotic depression (4, 5). As an “independent” condition,
dysthymic disorder was defined as a subsyndromal
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CRISTANCHO ET AL.
Table 1.
DSM-IV Criteria for Dysthymic Disordera
A. Depressed mood for most of the day, for more days than not, as indicated either by subjective account or observation by others, for at least
2 years.
Note: In children and adolescents, mood can be irritable and duration must be at least 1 year.
B. Presence, while depressed, of two (or more) of the following:
1. Poor appetite or overeating
2. Insomnia or hypersomnia
3. Low energy or fatigue
4. Low self-esteem
5. Poor concentration or difficulty making decisions
6. Feelings of hopelessness
D. No Major Depressive Episode has been present during the first 2 years of the disturbance (1 year for children and adolescents); i.e. the
disturbance is not better accounted for by chronic Major Depressive Disorder, or Major Depressive Disorder in Partial Remission.
Note: There may have been a previous Major Depressive Episode provided there was a full remission (no significant signs or symptoms for
2 months) before development of the Dysthymic Disorder. In addition, after the initial 2 years (1 year in children or adolescents) of Dysthymic
Disorder, there may be superimposed episodes of Major Depressive Disorder, in which case both diagnoses may be given when the criteria are
met for a Major Depressive Episode.
CLINICAL
SYNTHESIS
C. During the 2-year period (1 year for children or adolescents) of the disturbance, the person has never been without the symptoms in Criteria A
and B for more than 2 months at a time.
E. There has never been a Manic Episode, a Mixed Episode, or a Hypomanic Episode, and criteria have never been met for Cyclothymic Disorder.
F. The disturbance does not occur exclusively during the course of a chronic Psychotic Disorder, such as Schizophrenia or Delusional Disorder.
G. The symptoms are not due to the direct physiological effects of a substance (e.g. a drug of abuse, a medication) or a general medical condition
(e.g. hypothyroidism).
H. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
Specify:
Early Onset: if onset is before age 21 years
Late Onset: if onset is age 21 years or older
Specify (for most recent 2 years of Dysthymic Disorder):
With Atypical Features
a
Adapted from Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994 (7).
state (i.e., too few symptoms to meet criteria for
a major depressive episode), with a protracted duration of at least 2 years in adults. It was characterized by an insidious onset, often in childhood or
adolescence, and a persistent, intermittent, or
fluctuating course (6). As seen in Table 1, the diagnosis of dysthymic disorder requires the presence
of predominantly depressed mood for at least 2
years (criterion A; irritability and 1-year duration
will satisfy criteria in children and adolescents) and
at least two or more criterion B features (i.e., change
in appetite, change in sleep, decreased energy, low
self-esteem, difficulties concentrating or making
decisions, or hopelessness). The presence of either a
symptom-free period lasting longer than 2 months
or the presence of a major depressive episode during
the first 2 years of the onset of the condition (1 year
for children and adolescents) rule out the diagnosis
(criterion C and D). Although some people with
bipolar disorder also experience longstanding mild
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depressions, the diagnosis of dysthymic disorder
cannot be made when an individual has a history
of mania, hypomania, mixed affective episodes, or
cyclothymia (criterion E). A history of psychotic
symptoms does not rule out a diagnosis of dysthymic disorder as long as mood symptoms are not
exclusively present during psychotic episodes (criterion F). As is true of other DSM-IV affective
disorders diagnoses, the symptoms should not be
a direct consequence of substance abuse or a medical condition, and a significant functional impairment should be present as a consequence of the
symptoms (criterion G and H) (7). In the current
classification, several specifiers can be used to further describe the disorder, including early versus
late onset (21 years being the cutoff point) and
presence of atypical features (7). The distinction
between early- and late-onset dysthymia is thought
to have particularly important prognostic implications (7).
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CRISTANCHO ET AL.
DIFFERENTIAL
DIAGNOSIS
Clinical similarities and frequent coexistence
with the various forms of major depressive disorder
(MDD) can lead to diagnostic difficulties. In this
regard, adults who meet criteria for MDD can be
diagnosed with dysthymic disorder as long as the
dysthymic disorder has been evident for at least 2
years before the onset of the major depressive episode or the major depressive episode has been in
full remission for 2 months before onset of dysthymia. In fact, across a lifetime, most people with
dysthymic disorder will experience superimposed
major depressive episodes and, conversely, at least
20% of people with MDD will have a history of
antecedent dysthymic disorder (8). Whether such
“double depressions” are a truly unique entity or
more simply reflect the waxing and waning of
single condition has been a topic of some interest
to mood disorders nosologists for the past 30
years.
As illustrated above, to diagnose dysthymic disorder one should consider not only the chronicity of
the symptoms but also the characteristic number and
intensity of the symptoms. By convention, a hallmark of dysthymic disorder is that the symptom
burden across any and all 2-week intervals is below
the threshold for diagnosis of MDD. This convention, in turn, is why the specifier “chronic” is used to
describe major depressive episodes that last 2 years
or longer (i.e., chronic major depressive episode) in
people with MDD or bipolar affective disorder (7).
Patients with MDD can also have a chronic course
of illness because of failure to achieve full remission
of symptoms. As such, they would not meet criteria for dysthymia or chronic major depressive
episode, but instead they would be diagnosed as
recurrent major depression without full interepisode recovery (7).
Although the presence of chronic depressive
symptoms is no longer thought of as a form of
personality disorder, axis II conditions are not uncommon among people with early onset chronic
forms of depression, with cluster C or “internalizing”
personality disorders being the most common. In
one study of patients with chronic forms of MDD,
nearly one-half of the patients had at least one cooccurring personality disorder, even though patients
with borderline and more severe antisocial personality disorders were excluded from this study (9).
Not all conditions associated with chronic depressive symptoms are classifiable as mood disorders. For example, entities such as prolonged
grief disorder and chronic adjustment disorder
with depressed mood can also present with protracted depressive symptoms but at this juncture
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are not formally considered forms of chronic depression.
The presence of medical conditions as perpetuating or etiologic factors should always be explored when evaluating a patient with chronic
depression. Such conditions include endocrine
disturbances (e.g., hypothyroidism, low testosterone,
or protracted perimenopausal changes), anemia,
hyponatremia, autoimmune disturbances, tumors
(e.g., pancreatic, brain, and lung cancer), infections
(including human immunodeficiency virus infection), and neurological conditions like epilepsy,
Parkinson’s disease, and multiple sclerosis. Chronic
mood symptoms can be caused or perpetuated by
the abuse of drugs or alcohol and can be induced
iatrogenically by antihypertensives, oral contraceptives, steroids, analgesics, antimicrobials, retinoic acid, benzodiazepines, and other medications
(10, 11).
DIAGNOSTIC
VALIDITY
The diagnostic validity of chronic forms of depression has been an area of controversy, with most
of the work done in patients with dysthymia. Biological research initially was used to help establish
the validity of dysthymia as a subtype of depressive
disorder. Findings that support a biological basis for
this condition included sleep cycle abnormalities that
are characteristic of MDD (reduced rapid eye movement [REM] latency, increased REM sleep, and abnormal theta bursts) and abnormalities in central
nervous system electrophysiological functions (electroencephalogram during waking state, electrodermal
activity, and evoked potentials) (12). Other markers
suggesting its biological independence from major
depressive disorder include differences in growth
hormone secretion and in hypothalamic pituitary
axis function (12). However, little has been found
when exploring for differences in demographic
variables, symptom patterns, treatment response or
family history between the different forms of
chronic depression (13). In light of that, the depressive disorders work group for DSM-5 has proposed the substitution of dysthymia for a broader
category named “chronic depression” (2). The
proposed criteria for DSM-V chronic depression are
the same as the DSM-IV criteria for dysthymic
disorder except for minor modifications to criteria
D and E, which are intended to decrease the impact
of the chronically depressed patient’s recall bias. The
proposed DSM-5 criteria focuses in the last 2 years
of symptoms (instead of the first 2) when exploring
the presence of chronic major depressive episode or
cyclothymia (2).
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PREVALENCE, IMPACT, AND COMORBIDITY
TREATMENT
Given the significant potential for deleterious
effects, chronic forms of depression should be
promptly recognized by healthcare and mental
health providers and aggressively treated.
As part of the zeitgeist to validate dysthymic disorder and other forms of chronic depression as mood
disorders, a number of randomized clinical trials of
antidepressants were conducted in the 1980s and
1990s. The first large-scale, randomized, placebocontrolled trial of an antidepressant for chronic
forms of depression was published in the late 1980s
by Kocsis et al. and reported an encouraging 59%
response rate with imipramine (as compared with
a 13% response rate with placebo) in a sample of 76
subjects in which 84% had courses greater than 5
years (25). Significant benefits were subsequently
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CLINICAL
SYNTHESIS
It is estimated that chronic forms of depression
affect 3%–6% of adults in the United States (14,
15). Chronic courses are expected in up to 20% of
patients with major depressive disorder (14, 15).
Prevalence of dysthymic disorder is relatively high in
primary care settings (7%) (16) and even higher in
psychiatric outpatient clinics (36%) (17). Chronic
courses of depressive symptoms are associated with
a higher degree of occupational and psychosocial
maladjustment and more frequent suicide attempts
than the more episodic forms of depression (18).
For example, although by definition dysthymia is
a condition of low-grade severity, it is associated
with significant functional impairment. In fact,
patients with dysthymia are more likely to have
supplemental social security income and Medicaid
status and less likely to work full time than individuals with nonchronic forms of MDD (19). Patients with dysthymic disorder are more likely to
have coexisting axis I conditions with a comorbidity
rate of up to 75% in which major depressive disorder, anxiety disorders, and substance abuse are more
frequently present (20). By itself, dysthymia is a risk
factor for the development of a major depressive
episode and (21) its presence is associated with poorer
prognosis and more treatment resistance in patients
with major depressive disorder (22).
The presence of chronic depressive symptoms,
even when subthreshold for major depressive episode, is associated with worse prognosis in patients
with coronary heart disease (23) and pregnancy.
Newborns of mothers with dysthymia are more
likely to have shorter gestational age, a lower birth
weight, shorter birth length, and less optimal obstetric outcomes (24).
reported in a large scale, placebo-controlled multicenter study contrasting imipramine and the selective serotonin reuptake inhibitor (SSRI) sertraline
(26). In that study, both types of antidepressants
were effective, with the SSRI showing better tolerability. The advantage of active pharmacotherapy
over placebo in the treatment of chronic forms of
depression has been replicated by other investigators
and most recently confirmed by meta-analyses. In
one recent meta-analysis, for example, Levkovitz
et al. reported response rates of up to 52.4% and
a number needed to treat of 4.4 was calculated in
a sample of 1,454 dysthymic patients receiving
monotherapy with a broad range of antidepressants
agents including imipramine, fluoxetine, sertraline,
and moclobemide (a reversible inhibitor of monoamine oxidase A that, although available in many
countries, is not approved for use in the United
States), as well as the experimental compounds
ritanserin and amisulpride (27). Antidepressant response rates in dysthymia are comparable to those of
patients with major depressive disorder even in the
presence of negative prognostic indicators such as
axis II comorbidities (9). Although the available
evidence does not identify a single best type of antidepressant for the treatment of chronic depression,
the evidence is strongest for tricyclic antidepressants
and selective serotonin reuptake inhibitors (28).
These classes of antidepressants may benefit different patients and those who do not respond to one
type may still benefit from an adequate trial of the
other class of medication. For example, in one study
of chronic forms of depression (average duration .6
years), patients showed similar response rates to an
initial, 12-week course of double-blind treatment
with either sertraline or imipramine monotherapy
(52% with sertraline and 51% with imipramine)
(29). Nonresponders were then switched to the alternate medications and over one-half responded
and about one-quarter remitted (29). As expected,
given its more favorable safety and tolerability profile, selective serotonin reuptake inhibitors are more
frequently used.
When antidepressants are effective, continuation
of treatment beyond acute response and remission is
necessary to lower the risk of relapse in patients with
chronic depression (30–32). It is not known whether treatment should be continued indefinitely or
can be tapered after an extended period of recovery without great hazard of recurrence. In practice, such decisions should be made on a case-by-case
basis, considering both the costs and side effects of
ongoing pharmacotherapy and the potential risks of
a recurrence following withdrawal of the antidepressant.
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CRISTANCHO ET AL.
Frequent comorbid personality disorders as well as
possible changes in personality resulting from years
or even decades of depression have long made psychotherapy an important consideration for individuals with chronic forms of depression. The
general range of response rates in small studies of
patients with double depression and dysthymia receiving cognitive behavioral therapy has been reported to be above 30% (33), and there is ample clinical
experience that many patients with longstanding
depressions can benefit from cognitive, behavioral,
interpersonal, and psychodynamic psychotherapies.
However, meta-analyses of randomized clinical
trials suggest that antidepressant medications (including sertraline, fluoxetine, and nortriptyline)
may—on average—convey greater symptomatic
benefits over psychotherapies across the first 3-4
months of treatment (34–36).
Although widely practiced and often recommended, combination therapy (i.e., medication plus
psychotherapy) has not always been shown in randomized controlled trials to convey a significant
advantage compared with medications alone in
randomized controlled trials. For example, in two
large trials of dysthymic disorder conducted in
Canada, no advantages for combining interpersonal
psychotherapy (IPT) (37) or group cognitive behavioral (38) therapies with sertraline were found in
comparison to pharmacotherapy with sertraline
alone. An advantage was found in a large study of
patients with chronic forms of MDD (681 subjects). In this trial, patients were randomly assigned
to 12 weeks of treatment with the antidepressant
nefazodone, a form of psychotherapy developed
specifically for chronic depression known as CBASP
(cognitive behavioral analysis system of psychotherapy), or their combination. Patients receiving
the monotherapies had a 48% response rate (i.e.,
drug and psychotherapy were almost identically
effective at week 12), whereas there was a 73% response rate in combination treatment group (18).
A similarly large advantage was shown for chronically depressed inpatients in a German study that
contrasted the combination of interpersonal psychotherapy (IPT) and treatment as usual (i.e.,
pharmacotherapy and milieu therapies) as compared with treatment as usual alone (39). However,
no advantage for combined treatment was observed
in a third trial known by the acronym REVAMP
(Research Evaluating the Value of Augmenting
Medication With Psychotherapy). This outpatient
study, which randomly assigned 491 patients with
chronic forms of major depression who had not
remitted with an initial prospective course of
algorithm-guided course of pharmacotherapy,
found that the addition of psychotherapy (either
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brief supportive psychotherapy or CBASP) to
medications did not result in significantly better
outcomes as compared with pharmacotherapy
alone (40). Nonetheless, psychotherapy remains
and important element when treating chronic
depression, and combination therapy continues
to be an appropriate option for many patients
with persistent and disabling depressive disorders
that have not responded to pharmacotherapy
alone (41).
CONCLUSIONS
As illustrated by this brief review and based on the
available evidence and our clinical experience,
chronic forms of depression are prevalent and even
those with low grade severity can lead to significant
functional impairment if untreated. Therefore
chronic depression should be considered when
evaluating patients with dysphoria even in the presence of significant characterological traits. Clinical
benefit from using psychopharmacologic agents
alone or in combination with psychotherapy for
the treatment of chronic depression is supported in
the literature and should be pursued when taking
care of patients with chronic depressive symptoms.
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NOTES
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