Pharmacotherapy of Autism Spectrum Disorder: Results from the Randomized BAART Clinical Trial.

The objective of this trial, Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART), was to provide support and guidance for an evidence-based approach for the selection and monitoring of initial pharmacotherapy in patients with autism by assessing predictors of efficacy, tolerability, and safety. This randomized double-blind parallel-group study was conducted in three academic medical centers and a single private pediatric practice. Eighty children or adolescents (aged 6-17 yrs) with autistic disorder were enrolled, and 61 patients were randomized to the study drug. Of those patients, 51 completed the 10-week trial, and 31 completed an optional 12-week blinded extension phase. All patients were treated with 2 weeks of placebo before random assignment to receive aripiprazole (31 patients) or risperidone (30 patients) for 10 weeks. Sixteen placebo responders (20%) were excluded from further analysis. Drug dosing followed U.S. Food and Drug Administration (FDA) labeling, and weekly dosage adjustments were allowed until week 4; patients were then maintained on a fixed dose for 6 additional weeks. Safety, physical, and psychological assessments were recorded weekly or every 2 weeks. No significant differences in severity of illness between the aripiprazole and risperidone groups were noted at baseline. All patients significantly improved on the Aberrant Behavior Checklist-Irritability subscale after 1 week and continued for the remaining 9 weeks and the extension phase. Improvement was greatest in the risperidone group at every assessment period and was statistically significantly better than that in the aripiprazole group at weeks 3 and 6 (p<0.05). No dose-limiting adverse events occurred during the dose-titration period. Mean weight gain in the aripiprazole group was significantly less than that in the risperidone group at week 4 (0.62 vs 1.38 kg, p=0.033) and week 10 (1.61 vs 3.31 kg, p<0.001), but the difference became nonsignificant for the 31 patients completing the 3-month extension phase (4.36 vs 5.55 kg, p=0.26). Pharmacotherapy of patients with autism spectrum disorder resulted in behavioral improvement within 1 week and lasted at least 22 weeks. Weight gain occurred to a greater degree with risperidone than aripiprazole initially, but the differences became nonsignificant by the end of the trial. Our trial supports previous results of drug efficacy and safety in patients with autism spectrum disorder from other trials and extends the evidence-based support for choosing an FDA-approved drug for initial pharmacotherapy for autism spectrum disorder.

Buspirone treatment of cannabis dependence: A randomized, placebo-controlled trial.

BACKGROUND: The purpose of this study was to evaluate the efficacy of buspirone, a partial 5-HT1A agonist, for treatment of cannabis dependence. METHODS: One hundred seventy-five cannabis-dependent adults were randomized to receive either up to 60mg/day of buspirone (n=88) or placebo (n=87) for 12 weeks combined with a brief motivational enhancement therapy intervention and contingency management to encourage study retention. Cannabis use outcomes were assessed via weekly urine cannabinoid tests. RESULTS: Participants in both groups reported reduced cannabis craving over the course of the study; however, buspirone provided no advantage over placebo in reducing cannabis use. Significant gender by treatment interactions were observed, with women randomized to buspirone having fewer negative urine cannabinoid tests than women randomized to placebo (p=0.007), and men randomized to buspirone having significantly lower creatinine adjusted cannabinoid levels as compared to those randomized to placebo (p=0.023). An evaluation of serotonin allelic variations did not find an association with buspirone treatment response. CONCLUSIONS: Buspirone was not more efficacious than placebo in reducing cannabis use. Important gender differences were noted, with women having worse cannabis use outcomes with buspirone treatment. Considerations for future medication trials in this challenging population are discussed.

Concordance of Direct and Indirect Measures of Medication Adherence in A Treatment Trial for Cannabis Dependence.

The current study compared adherence rates as measured by two indirect measurement methods (pill count and daily medication diary) to two direct measurement methods (urine riboflavin and serum 6-OH-buspirone level measurement) among participants (n = 109) in a medication treatment trial for cannabis dependence. Pill count and diary data showed high levels of percent agreement and strong kappa coefficients throughout the study. Riboflavin levels indicated lower level of percent in adherence during the study as compared to both pill count and self-report. In the subset of participants with 6-OH-buspirone levels (n = 58), the kappa coefficient also showed low to moderate agreement between the pill count and medication diaries with 6-OH-buspirone levels. In contrast to pill count and medication diaries, adherence as measured by riboflavin and 6-OH-buspirone significantly decreased over time. The findings from this study support previous work demonstrating that pill count and patient self-report of medication taking likely overestimate rates of medication adherence, and may become less reliable as the duration of a clinical trial increases.