Paroxetine versus clomipramine in adolescents with severe major depression: A double-blind, randomized, multicenter trial

Objective: To date, two randomized, double-blind trials of serotonin reuptake inhibitors (SRIs) have shown that antidepressant drugs are effective in treating adolescent depression. In contrast, tricyclic antidepressants (TCAs) are not superior to placebo. This has led to a serotonin hypothesis In this age group. This study explores this hypothesis and compares paroxetime, a specific SRI, with clomipramine, a TGA with SRI activity. Method. One hundred twenty-one adolescents (aged 12-20 years) with major depression were enrolled and randomized (stratified for age) to 20 or 40 mg at paroxetine or 75 mg or 150 mg of clomipramine for 8 weeks. Primary outcome measurements were the Clinical Global Impression (CGI) scale and the Montgomery and Asberg Depression Rating Scale (MADRS). Results: Of the 121 patients, 58 received clomipramine and 63 paroxetine. Based on intent-to-treat analysis, both agents had similar efficacy, with no effect of age; 48.3%. and 58.2% of the subjects receiving clomipramine and 65.1% and 59.3%. of those receiving paroxetine were rated responders on the MADRS and CGI scales, respectively. Study withdrawals were frequent in both groups (41% and 31%, respectively), but side effects were significantly more frequent with clomipramine (69% versus 49.20%, respectively, p =.027). Conclusion. Paroxetine and clomipramine exhibit similar efficacy in adolescent depression. These data support the serotonin hypothesis but do not confirm it in the absence of a placebo arm. Given the adverse event profile of clomipramine, specific SRIs should be preferred. However, more placebo-controtted studies are needed to establish definitively the efficacy of SRIs in this age group.