Fluvoxamine is more effective than placebo in the short-term treatment of the symptoms of autistic disorder in adults. Controlled studies of fluvoxamine and other potent and selective serotonin uptake inhibitors seem warranted in children and adolescents with autism.
The short-term efficacy and tolerability of sertraline for adults with pervasive developmental disorders (PDDs) were assessed in this investigation. Forty-two adults with PDDs (autistic disorder, N = 22; Asperger's disorder, N = 6; and PDD not otherwise specified [NOS], N = 14) participated in a 12-week, open-label, systematic trial of sertraline. Behavioral ratings of repetitive symptoms, aggression, and social relatedness were obtained at baseline and after 4, 8, and 12 weeks of sertraline administration. Twenty-four (57%) of 42 patients showed significant improvement, primarily in repetitive and aggressive symptoms. Statistically significant changes in measures of social relatedness did not occur. Patients with autistic disorder and PDD NOS did significantly better than those with Asperger's disorder. Based on global improvement item criteria from the Clinical Global Impression Scale, 15 of 22 (68%) patients with autistic disorder, none of six (0%) patients with Asperger's disorder, and 9 of 14 (64%) patients with PDD NOS were categorized as treatment responders. Sertraline was well tolerated; no adverse cardiovascular effects, extrapyramidal symptoms, or seizures were identified. These findings suggested that sertraline may be an effective treatment for interfering repetitive and aggressive symptoms in adults with PDDs. Definitive statements about the efficacy and tolerability of sertraline for treating adults with PDDs must await results from double-blind, placebo-controlled trials. These preliminary results should not be generalized to include children and adolescents with PDDs.
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.
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