Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis

Questions have been raised regarding the relative efficacy and tolerability of the different serotonin transport inhibitors in the treatment of obsessive-compulsive disorder. We compared the results from four large multicenter placebo-controlled trials of the serotonin transport inhibitors clomipramine hydrochloride (N = 520), fluoxetine hydrochloride (N = 355), fluvoxamine maleate (N = 320), and sertraline hydrochloride (N = 325) for the treatment of obsessive-compulsive disorder.

Effect size was calculated by subtracting the end-point drug treatment mean change from the end-point placebo mean change and dividing by the end-point pooled change standard deviation. A test for overall differences between effect sizes was conducted, followed by all possible pairwise comparisons. The Yale-Brown Obsessive Compulsive Scale was the primary outcome measure for all four studies.

All four agents were significantly more effective than placebo, with clomipramine significantly more effective than the other three treatments, which did not differ in effect size. A significantly greater percentage of patients treated with clomipramine were rated much or very much improved than were patients treated with fluoxetine, fluvoxamine, or sertraline.

While the results of this meta-analysis support the superiority of clomipramine, head-to-head, double-blind comparisons of these compounds would be the best test of comparative efficacy and tolerability.