Cognitive Effects of Risperidone in Children with Autism and Irritable Behavior

Objective: The objective of this research was to explore the effects of risperidone on cognitive processes in children with autism and irritable behavior. Method: Thirty-eight children, ages 5-17 years with autism and severe behavioral disturbance, were randomly assigned to risperidone (0.5 to 3.5 mg/day) or placebo for 8 weeks. This sample of 38 was a subset of 101 subjects who participated in the clinical trial; 63 were unable to perform the cognitive tasks. A double-blind placebo-controlled parallel groups design was used. Dependent measures included tests of sustained attention, verbal learning, hand-eye coordination, and spatial memory assessed before, during, and after the 8-week treatment. Changes in performance were compared by repeated measures ANOVA. Results: Twenty-nine boys and 9 girls with autism and severe behavioral disturbance and a mental age ≥18 months completed the cognitive part of the study. No decline in performance occurred with risperidone. Performance on a cancellation task (number of correct detections) and a verbal learning task (word recognition) was better on risperidone than on placebo (without correction for multiplicity). Equivocal improvement also occurred on a spatial memory task. There were no significant differences between treatment conditions on the Purdue Pegboard (hand-eye coordination) task or the Analog Classroom Task (timed math test). Conclusion: Risperidone given to children with autism at doses up to 3.5 mg for up to 8 weeks appears to have no detrimental effect on cognitive performance

Extended-Release Guanfacine Does Not Show a Large Effect on Tic Severity in Children with Chronic Tic Disorders

Objective: To evaluate the tolerability, safety, and preliminary efficacy of extended-release guanfacine in children with chronic tic disorders, including Tourette's disorder (collectively referred to as CTD). Methods: This was a multisite, 8-week, randomized, double-blind, placebo-controlled trial. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS) total score. Key secondary outcomes included the Improvement item of Clinical Global Impressions-Improvement (CGI-I) scale and the Tic Symptom Self-report (TSSR). Adverse events were monitored at each visit. Results: Thirty-four subjects (23 boys and 11 girls) of ages 6 to 17 years (mean = 11.1 ± 3.1) with CTD were randomly assigned to extended-release guanfacine ( n  = 16) or placebo ( n  = 18). At baseline, the mean YGTSS total score was 26.3 ± 6.6 for the guanfacine group versus 27.7 ± 8.7 for the placebo group. Within the guanfacine group (mean final daily dose of 2.6 ± 1.1 mg, n  = 14), the mean YGTSS total score declined to 23.6 ± 6.42 [ t (15) = 1.84, p  = 0.08; effect size = 0.35]. The results were similar in the placebo group with a score of 24.7 ± 10.54 at week 8 [ t (17) = 1.83, p  = 0.08; effect size = 0.38]. There was no significant difference in the rate of positive response on the CGI-I between the guanfacine group and placebo (19% [3/16] vs. 22% [4/18], p  = 1.0). The most common adverse events were fatigue, drowsiness, dry mouth, headache, and irritability. Two subjects in the guanfacine group discontinued early—one because of an adverse event (depressed mood) and one because of lack of efficacy; two subjects in the placebo group discontinued because of lack of efficacy. Conclusions: This pilot study did not confirm a clinically meaningful effect size within the guanfacine group. These results do not support the launch of a larger efficacy trial for tics in children and adolescents with CTD