Clomipramine-induced mania in unipolar depression

Manic behavior during randomly assigned treatment with clomipramine (chlorimipramine) or amitriptyline hydrochloride developed in seven of 50 hospitalized unipolar depressed patients. Six of the 25 clomipramine-treated patients became manic. Only one patient in the amitriptyline-treated group developed manic behavior. The switch into mania occurred at the mean age of 63, much later than the reported age of risk for mania. Significant correlations were observed between the age at onset of mania, the number of days of clomipramine treatment, and the duration of the manic episode. We hypothesize that such a switch into mania in unipolar patients is triggered by the psychopharmacological effect of clomipramine through an alleged change in activity of the central dopamine and serotonin systems.