Clinical trials of dysthymic disorder have been plagued by much variability in duration of treatment, measures of improvement, and patient selection. Overall, however, it appears that response to treatment is better than that seen with placebo and may, in some cases, be as good as is seen in major depression.
In a double-blind, placebo-controlled study of 50 patients with dysthymic disorder lasting seven weeks, both imipramine and ritanserin (not available in the United States) were found to be significantly superior to placebo, with no significant differences between the two active drugs. The dropout rates were 31% for the imipramine group (associated with a high frequency of sedative and anticholinergic side effects), 41% for the placebo group (probably due to lack of response), and only 20% for the ritanserin group.
| Table 2. | |||
| DSM-IV Criteria for Major Depression Episode |
| A. | Five (or more) of the following symptoms have been present during the same two-week period and represent a change from previous functioning; at least one of the symptoms is either depressed mood or loss of interest or pleasure. Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations. | ||||
| (1) | Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful).Note: In children and adolescents, can be irritable mood. | ||||
| (2) | Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others). | ||||
| (3) | Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day.Note: In children, consider failure to make expected weight gains. |
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| (4) | Insomnia or hypersomnia nearly every day | ||||
| (5) | Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) | ||||
| (6) | Fatigue or loss of energy nearly every day | ||||
| (7) | Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) | ||||
| (8) |
Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) |
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| (9) | Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide | ||||
| B. |
The symptoms do not meet criteria for a Mixed Episode. |
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| C. | The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. | ||||
| D. | 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). | ||||
| E. | The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. | ||||
In a randomized, double-blind comparison of fluoxetine and placebo in 35 patients diagnosed with dysthymic disorder, 32 patients completed the eight-week study. Three of the patients in the fluoxetine group dropped out. Ten of the remaining 16 patients (62.5%) receiving fluoxetine (average daily dose of 32.7 mg) responded to treatment; however, only one displayed a complete remission. The others improved but experienced residual symptoms. Only 3 of 16 patients (19%) receiving placebo responded to treatment. Side effects in the fluoxetine group included nervousness and shakiness (29.4%), muscle and joint pain (23.5%), sweating (17.6%), and sexual dysfunction (17.6%).
The most recent large-scale study of dysthymic disorder included 410 patients with a duration of illness of at least five years (average duration of 30 years). Patients having previously failed to respond to imipramine or to adequate trials of any two antidepressants were excluded. Of the 410 patients randomly assigned to receive sertraline, imipramine, or placebo, 310 completed the 12-week study. Fifty-nine percent of the 134 patients receiving sertraline (average daily dose of 140 mg) and 64% of the 136 patients receiving imipramine (average daily dose of 199 mg) were classified as responders (i.e., “much improved” or “very much im-proved”). Of the 140 patients receiving placebo, 44% were considered responders. Complete remission, defined by much more stringent criteria (i.e., no longer meeting the diagnostic criteria for dysthymia and scoring 0 on the depression item of the Hamilton Depression Rating Scale), was seen in 50% of the sertraline group, 44% of the imipramine group, and 28% of the placebo group. In all measures of psychosocial functioning, whether clinician-rated or self-rated, there was greater improvement in the patients receiving sertraline and imi-pramine than those receiving placebo. Following treatment, 61% of patients taking sertraline, 58% of those taking imipramine, and 45% of those taking placebo were assessed as showing little or no psychosocial impairment.
Although long-term studies of chronic depression have included patients with “double depression” as well as pure dysthymic disorder, results indicate that maintenance treatment may be beneficial in reducing relapse rates. When 25 chronically depressed patients who had participated in a six-week trial of imipramine (daily dosage range of 100–300 mg/day) were assessed an average of 40 weeks following entry into the original study, eight of the nine patients who had initially responded to imipramine were still classified as responders. Five of the nine were still taking imipramine. One was taking desipramine, and three were taking no medication. In another study, relapse rates after two years in chronically depressed patients receiving desipramine maintenance were only 11% compared to 52% in patients receiving placebo. In addition, if a patient responds well to a medication and relapse does occur after discontinuation of the agent, it appears that there is a high probability that a second remission can be achieved following reinstitution of the same medication. This was demonstrated in 11 of 12 (92%) dysthymic patients who had responded to a medication and completed a period of maintenance treatment.
Conclusion
Dysthymic disorder is a chronic depressive disorder which has a significant impact on psychosocial and occupational functioning. With an estimated prevalence of between 3% and 6%, it is generally underdiagnosed and undertreated. Availability of data regarding efficacy of antidepressant treatment is limited by relatively small numbers of patients studied, inexact patient selection criteria, high dropout rates, and, at times, relatively high rates of response to placebo. However, overall, it appears that antidepressants are more efficacious than placebo and that both mood and psychosocial functioning can be significantly improved by pharmacotherapy. Although additional large-scale, long-term, diagnosis-specific studies need to be completed and predictors of response need to be identified, it seems that antidepressant therapy should be seriously considered in any patient with dysthymic disorder that is sufficiently severe and persistent to cause impairment in psychosocial functioning.