Faculty Bibliography

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

OBJECTIVE: To assess critically the short-term efficacy and safety of carbamazepine in the reduction of aggressiveness in children with diagnosed conduct disorder. METHOD: Subjects were children aged 5 to 12 years who were hospitalized for treatment-resistant aggressiveness and explosiveness and who had diagnosed conduct disorder. The study was double-blind and placebo-controlled, using a parallel-groups design. Following a 2-week placebo baseline period, children who met the aggression criteria were randomly assigned to treatments for 6 weeks; the study ended with a 1-week posttreatment placebo period. Multiple raters rated the children independently, using multiple rating scales under four conditions. The main outcome measures included the Overt Aggression Scale, the Global Clinical Judgments (Consensus) Scale, and the Children's Psychiatric Rating Scale. RESULTS: Twenty-two children, aged 5.33 to 11.7 years, completed the study. Carbamazepine was not superior to placebo at optimal daily doses ranging from 400 to 800 mg, mean 683 mg, at serum levels of 4.98 to 9.1 micrograms/mL. Untoward effects associated with administration of carbamazepine were common. CONCLUSIONS: In this modest sample of children, the superiority of carbamazepine over placebo in reducing aggressive behavior was not demonstrated