Mauricio Silva de Lima, Joanna Moncrieff, Bernardo GO Soares

Dysthymia is a depressive disorder of chronic nature but of lower severity than major depression. Depressive symptoms are more or less continuous for at least two years. Patients with this disorder experience considerable social dysfunction and disability and are more likely than the general population to use general medical services and to take non-specific psychotropic drugs. Examining the use of pharmacotherapy for this condition is of critical importance. The aim of this review was to conduct a systematic review of all randomised controlled trials comparing drugs and placebo for the treatment of dysthymia. Electronic searches of The Cochrane Library, MEDLINE, EMBASE, PsycLIT, biological abstracts and LILACS; reference searching; personal communication; conference abstracts; unpublished trials from the pharmaceutical industry; book chapters on the treatment of depression. All randomised controlled trials that focused on the use of drugs versus placebo for dysthymic patients were included.Exclusion criteria were: non-randomised controlled trials, a mixture of major depression and dysthymia (trials not providing separate data) and depression secondary to other disorders (e.g. substance abuse). The reviewers extracted the data independently. In order to achieve an intention-to-treat analysis it was assumed, when not reported in the trial, 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 and 95% confidence intervals (CI) of dichotomous data were calculated with the random-effects model. Where possible, number needed to treat and number needed to harm were estimated, taking the reciprocal of the absolute risk reduction. Currently the review includes 29 trials, 17 reporting data for the main outcome measures. Similar results were obtained in terms of efficacy for different groups of drugs, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors and other drugs (sulpiride, amineptine, and ritanserin). The pooled relative risk for absence of treatment response was 0.68 (95% CI 0.59 to 0.78) for tricyclic antidepressants and the number needed to treat was 4.3 (95% CI 3.2 to 6.5). Selective serotonin reuptake inhibitors showed similar relative risk for this outcome: 0.68 (95% CI 0.56 to 0.82), the number needed to treat was 5 (95% CI 3.3 to 9). Concerning monoamine oxidase inhibitors, the relative risk was 0.59 (95% CI 0.48 to 0.71) and the number needed to treat was 2.9 (95% CI 2.2 to 4.3). Other drugs (amisulpiride, amineptine and ritanserin) showed similar results in terms of absence of treatment response. Using more stringent criteria for improvement, i.e. full remission, the results were unchanged. Patients treated on tricyclic antidepressants were more likely to report adverse events, compared with placebo. Drugs are effective in the treatment of dysthymia with no differences between and within drug classes. 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.