Risperidone in children and adolescents with pervasive developmental disorder: pilot trial and follow-up

Dopamine receptor antagonists, particularly haloperidol, have been the most effective medications in currently available double-blind placebo-controlled studies for treating the disruptive behaviors often associated with pervasive developmental disorder (PDD). The rationale for trying risperidone in this population includes its dopamine-blocking activity; its seemingly lower incidence of tardive dyskinesia when compared to standard neuroleptics; the possibility that risperidone may ameliorate the social withdrawal of PDD, as it does the negative symptoms in schizophrenia; and substantial effects on serotonergic neurotransmission, which has been shown to be dysregulated in some patients with PDD. This study was an open-label pilot trial of risperidone in 6 subjects (aged 7-14 years, mean = 10.7) who met DSM-III-R criteria for a PDD diagnosis. The mean optimal dose was 2.7 mg daily (range 1-6). Mean duration of risperidone administration was 5.2 months (range 1-8). Despite the small sample size, risperidone treatment appeared to be associated with significant improvements in ratings of angry affect (p = 0.04) and lability of affect (p = 0.03) and with a trend (p = 0.10) toward a reduction of mean hyperactivity scores. Clinical Global Improvement scale ratings were statistically significant (p < 0.001). Increased sociability was reported in 3 subjects by their parents and family following the study. Three patients continued on risperidone for over 2 years, and none showed any loss of its apparent therapeutic effects. Weight gain was observed in 5 of 6 patients, with a median increase of 5.4 kg (12 lbs) in 7 weeks. Other side effects included transient sedation, increased salivation, and stereotypies. One child showed a worsening of pre-existing tic and phobic symptoms after 5 months of successful monotherapy. No loss of therapeutic effect was noted in the 3 subjects who remained on risperidone for over 2 years, but 1 patient developed hepatotoxicity and another developed withdrawal dyskinesia, similar to her prior experience with haloperidol. Overall, 5 of the 6 patients derived significant clinical benefits from risperidone. Pharmacologic alternatives for treating behavioral symptoms in PDD are need, and risperidone may be a promising possibility.