CLOMIPRAMINE IN ADULTS WITH PERVASIVE DEVELOPMENTAL DISORDERS - A PROSPECTIVE OPEN-LABEL INVESTIGATION

The purpose of this investigation was to determine the short-term effi cacy and tolerability of clomipramine in a consecutive series of adult s with pervasive developmental disorders (PDDs). Thirty-five adults wi th PDDs (DSM-IV), 16 of whom were nonverbal, entered a 12-week prospec tive open-label trial of clomipramine. The initial sample included 18 patients with autistic disorder, 6 patients with Asperger's disorder, and 11 patients with pervasive developmental disorder not otherwise sp ecified (PDDNOS). Behavioral ratings were obtained at baseline and aft er 4, 8, and 12 weeks of clomipramine. Eighteen (55%) of the 33 patien ts who completed the trial were categorized as treatment responders ba sed on scores of ''much improved'' or ''very much improved'' on the Cl inical Global Impression (CGI) global improvement item (p < 0.001). Te n (63%) of 16 patients with autistic disorder, 2 (33%) of 6 patients w ith Asperger's disorder, and 6 (55%) of 11 patients with PDDNOS were c onsidered responders to clomipramine treatment. In those 18 patients, clomipramine significantly reduced total repetitive thoughts and behav ior (p < 0.001) and also aggression (p < 0.001), and improved some asp ects of social relatedness, such as eye contact and verbal responsiven ess (p < 0.001). Change in these specific symptom clusters over time w as not related to DSM-IV subtype of PDD. The level of autistic behavio r, as measured by the Autism Behavior Checklist (ABC) score, and full- scale intelligence quotient (IQ) were not significantly associated wit h global treatment response. Whereas clomipramine was well tolerated b y most patients, 13 had clinically significant adverse effects. Three patients had seizures during clomipramine treatment, including 2 who h ad prior seizure disorders and were taking anticonvulsants. Of the 32 patients who had no history of prior seizures, only 1 had a seizure du ring clomipramine treatment. There were no adverse cardiovascular or e xtrapyramidal effects. All responders continued on clomipramine after completion of the study. The results of this open-label trial suggest that clomipramine may be an effective drug for reducing repetitive tho ughts and actions and aggressive behavior and for improving some eleme nts of social behavior, such as eye contact and verbal responsivity in adults with PDDs, Careful monitoring of adverse effects, particularly seizures, is warranted. Although an electroencephalogram (EEG) is not mandatory in patients with PDD prior to clomipramine treatment, we re commend that patients with PDD and a history of seizures be treated in itially with a selective serotonin uptake inhibitor rather than with c lomipramine. The findings of this study require replication in a doubl e-blind placebo-controlled investigation before definitive statements of efficacy and tolerability can be made.