Pharmacotherapy of dysthymic and chronic depressive disorders: overview with focus on moclobemide

Chronic depression was once considered untreatable pharmacologically. Open studies conducted around 1980 demonstrated efficacious results with tricyclics, classical MAOIs and lithium in 45% of cases. The subsequent delineation of dysthymia in DSM-III and its future editions as well as ICD.10, facilitated controlled trials in subjects with "pure dysthymia" and those with superimposed major depression (so-called "double-depression"). TCAs, SSRIs, RIMA, and benzamides have all proven effective in an average of 65% vs. an average of 25% with placebo. Well tolerated compounds--e.g. moclobemide, sertraline and desipramine--may permit the long-term clinical management of this spectrum of dysthymic and related conditions. Patients with "lifetime pure dysthymia" tend to respond more slowly to antidepressants than those with concurrent major depression ("double-depression") or those with "pure dysthymia" but with history of major depressive episodes. Chronicity is now well established: indeed discontinuation of antidepressants in a 4-year maintenance study has resulted in 89% rate of relapse. Dysthymia is a disabling condition and high doses of antidepressants are needed to achieve full recovery.