Clomipramine in Adults with Pervasive Developmental Disorders: A Prospective Open-Label Investigation

Abstract

The purpose of this investigation was to determine the short-term efficacy and tolerability of clomipramine in a consecutive series of adults with pervasive developmental disorders (PDDs). Thirty-five adults with PDDs (DSM-IV), 16 of whom were nonverbal, entered a 12-week prospective 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 specified (PDDNOS). Behavioral ratings were obtained at baseline and after 4, 8, and 12 weeks of clomipramine. Eighteen (55%) of the 33 patients who completed the trial were categorized as treatment responders based on scores of "much improved" or "very much improved" on the Clinical Global Impression (CGI) global improvement item (p < 0.001). Ten (63%) of 16 patients with autistic disorder, 2 (33%) of 6 patients with Asperger's disorder, and 6 (55%) of 11 patients with PDDNOS were considered responders to clomipramine treatment. In those 18 patients, clomipramine significantly reduced total repetitive thoughts and behavior (p < 0.001) and also aggression (p < 0.001), and improved some aspects of social relatedness, such as eye contact and verbal responsiveness (p < 0.001). Change in these specific symptom clusters over time was not related to DSM-IV subtype of PDD. The level of autistic behavior, as measured by the Autism Behavior Checklist (ABC) score, and full-scale intelligence quotient (IQ) were not significantly associated with global treatment response. Whereas clomipramine was well tolerated by most patients, 13 had clinically significant adverse effects. Three patients had seizures during clomipramine treatment, including 2 who had prior seizure disorders and were taking anticonvulsants. Of the 32 patients who had no history of prior seizures, only 1 had a seizure during clomipramine treatment. There were no adverse cardiovascular or extrapyramidal 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 thoughts and actions and aggressive behavior and for improving some elements 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 recommend that patients with PDD and a history of seizures be treated initially with a selective serotonin uptake inhibitor rather than with clomipramine. The findings of this study require replication in a double-blind placebo-controlled investigation before definitive statements of efficacy and tolerability can be made.

Medications for Adolescents and Young Adults With Autism Spectrum Disorders: A Systematic Review

“…Four studies were fair quality, 5-7,11 and 4 were poor. 4,[8][9][10] The most consistent findings were identified for antipsychotic medications. An RCT studying risperidone found improvements in aggression, repetitive behavior, sensory motor behaviors, and overall behavioral symptoms.…”

“…Of these, 5 were randomized controlled trials (RCTs) and 3 were case series. We located 3 studies addressing antipsychotic medications [4][5][6] ; 5 studies addressing serotonin reuptake inhibitor (SRI) medications 5,[7][8][9][10] ; and 1 study addressing the opioid receptor antagonist naltrexone. 11 Tables 3 and 4 summarize study characteristics and key results.…”

“…5,[7][8][9][10] One fair-quality RCT 7 investigated the efficacy of fluvoxamine in adults with autistic disorder. Participants were not receiving any psychotropic medications for at least 6 weeks before starting the trial.…”

“…One poor-quality study 9 agitation (n = 5), insomnia (n = 4), elated affect (n = 4), decreased appetite (n = 4), and increased screaming (n = 2).…”

“…5 Three case series of SRIs were also identified, including sertraline, fluoxetine, and clomipramine, with each study reporting some benefit to treatment. [8][9][10] A recent study not meeting criteria for this review also contributes to the limited data on SRIs. Hollander et al 14 reported a placebo-controlled RCT of fluoxetine that included 37 individuals with ASD (mean age: 34.31 years).…”