Clomipramine versus haloperidol in the treatment of autistic disorder: A double-blind, placebo-controlled, crossover study

Clomipramine, haloperidol, and placebo were compared with baseline in the t reatment of autism, and overall outcome, specific symptoms, and side effect s were examined. It was hypothesized that clomipramine would be better tole rated than haloperidol and prove superior on a measure of stereotypy. Indiv iduals with a DSM-TV diagnosis of autistic disorder (mean age, 16.3 years; range, 10-36 years) were randomly assigned, by using a Latin square design, to the following 7-week trials: placebo, clomipramine (mean daily dose, 12 8.4 mg; range, 100-150 mg), or haloperidol (mean daily dose, 1.3 mg; range, 1-1.5 mg). Data on 36 subjects were analyzed and taken together; the resul ts favored haloperidol. In those patients who were able to complete a full therapeutic trial, clomipramine proved comparable to haloperidol in terms o f improvement compared with baseline. However, significantly fewer individu als receiving clomipramine versus haloperidol were able to complete the tri al(37.5% vs. 69.7%,respectively) for reasons related to both side effects a nd efficacy or behavior problems. In the intent-to-treat sample, which is p erhaps more clinically relevant, only haloperidol proved superior to baseli ne on a global measure of autistic symptom severity, as well as specific me asures for irritability and hyperactivity. Clomipramine did not seem more e ffective on a measure of stereotypy, nor was it better tolerated.