June 1993

A Double-blind Comparison of Clomipramine, Desipramine, and Placebo in the Treatment of Autistic Disorder

Author Affiliations

From the Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Md.

Arch Gen Psychiatry. 1993;50(6):441-447. doi:10.1001/archpsyc.1993.01820180039004

Objective:  To determine whether clomipramine hydrochloride, a serotonin reuptake blocker with unique antiobsessional properties, is differentially effective for obsessivecompulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent, desipramine hydrochloride.

Design:  Following a 2-week, single-blind placebo washout phase, 12 autistic subjects completed a 10week, double-blind, crossover comparison of clomipramine and placebo, and 12 different subjects completed a similar comparison of clomipramine and desipramine.

Setting:  Outpatient clinic.

Patients:  A referral sample of 30 male and female autistic patients were enrolled, and 24 completed the study.

Measures:  Key outcome measures were the Autism Relevant Subscale of the Children's Psychiatric Rating Scale, the Modified Comprehensive Psychopathological Rating Scale—Obsessive-Copulsive Disorder Subscale, and the Clinical Global Impressions Scale.

Results:  Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms (including stereotypies), anger, and compulsive, ritualized behaviors (P<.05), with no differences between desipramine and placebo. Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity.

Conclusion:  Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.