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.

Does conduct disorder mediate the development of substance use disorders in adolescents with bipolar disorder? A case-control family study.

BACKGROUND: Recent work has highlighted important relationships among conduct disorder (CD), substance use disorders (SUD), and bipolar disorder in youth. However, because bipolar disorder and CD are frequently comorbid in the young, the impact of CD in mediating SUD in bipolar disorder youth remains unclear. METHOD: 105 adolescents with DSM-IV bipolar disorder (mean +/- SD age = 13.6 +/- 2.50 years) and 98 controls (mean +/- SD age = 13.7 +/- 2.10 years) were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and SUD. The study was conducted from January 2000 through December 2004. RESULTS: Among bipolar disorder youth, those with CD were more likely to report cigarette smoking and/or SUD than youth without CD. However, CD preceding SUD or cigarette smoking did not significantly increase the subsequent risk of SUD or cigarette smoking. Adolescents with bipolar disorder and CD were significantly more likely to manifest a combined alcohol plus drug use disorder compared to subjects with bipolar disorder without CD (chi(2) = 11.99, p < .001). CONCLUSIONS: While bipolar disorder is a risk factor for SUD and cigarette smoking in a sample of adolescents, comorbidity with preexisting CD does not increase the risk for SUD. Further follow-up of this sample through the full risk of SUD into adulthood is necessary to confirm these findings.

A pilot study of the effects of atomoxetine on driving performance in adults with ADHD.

OBJECTIVE: There is a high risk of vehicular crashes, traffic citations, and poorer driving performance in adults with ADHD. This pilot study examines the value of a new nonstimulant (atomoxetine) for improving the driving performance of adults with ADHD. METHOD: Atomoxetine (1.2 mg/kg daily for 3 weeks) and a placebo are studied on 18 adults with ADHD (M age = 37 years) using ratings of ADHD symptoms, impairment, and safe driving behavior; a virtual reality driving simulator; and ratings of simulator performance. RESULTS: Atomoxetine improves self-ratings of ADHD symptoms, impairments, safe driving behavior, and simulator driving performance. No effects of atomoxetine are evident on others' ratings of driving behavior or on the simulator. Practice effects on the simulator may have obscured those drug effects. CONCLUSION: The authors find a mixed pattern of results such that atomoxetine warrants further study for its effects on driving in this high-risk population.

Reduced temporal lobe volume in early onset conduct disorder.

Regional brain volumes derived from magnetic resonance imaging (MRI) scans from 10 youths with early onset conduct disorder and 10 healthy controls matched for age, sex and handedness were compared to determine whether prefrontal or temporal lobe brain volumes differed in the two groups. Right temporal lobe and right temporal gray matter volumes were significantly reduced in subjects with conduct disorder compared with controls. Prefrontal volumes in subjects with conduct disorder were 16% smaller than in controls, but the difference did not reach statistical significance. Early onset conduct disorder without substance abuse comorbidity was also significantly associated with smaller right temporal gray volumes. Further investigation of both the temporal and frontal localizations of the pathophysiology of early onset conduct disorder is warranted in larger samples.

Cigarette smoking and psychiatric comorbidity in children and adolescents.

OBJECTIVE: To review the current state of knowledge of psychiatric comorbidity in adolescent cigarette smokers. METHOD: assisted literature search was conducted and seminal articles were cross-referenced for comprehensiveness of the search. For each disorder, a synopsis of knowledge in adults is provided and compared with the knowledge in adolescents. RESULTS: Psychiatric comorbidity is common in adolescent cigarette smokers, especially disruptive behavior disorders (such as oppositional defiant disorder, conduct disorder, and attention-deficit/hyperactivity disorder), major depressive disorders, and drug and alcohol use disorders. Anxiety disorders are modestly associated with cigarette smoking. Both early onset (<13 years) cigarette smoking and conduct problems seem to be robust markers of increased psychopathology, including substance abuse, later in life. In spite of the high comorbidity, very few adolescents have nicotine dependence diagnosed or receive smoking cessation treatment in child and adolescent psychiatric treatment settings. CONCLUSIONS: There is increasing evidence for high rates of psychiatric comorbidity in adolescent cigarette smokers. Cigarette smoking in adolescence appears to be a strong marker of future psychopathology. Child and adolescent psychiatry treatment programs may be a good setting for prevention efforts and treatment, which should focus on both nicotine dependence and psychiatric disorders.

Hippocampal pathology in two mentally ill paraphiliacs.

Paraphilias or disorders of sexual behavior have markedly increased in prevalence during the last decade. Until now no published neuropathological studies on paraphilia have appeared in the medical literature. A computerized search was done on all available medical and autopsy records of a large urban hospital (St. Elizabeths Hospital, Washington, DC) for any mention of deviant sexual behavior. Cases were then reviewed for presence of a history consistent with DSM-IV diagnoses of paraphilia. Two such cases were identified. Neuropathological examination in both cases revealed simple cell atrophy of pyramidal cells confined to different hippocampal subfields. Reactive astrocytosis was present in the outer strata of the affected regions. The pathological changes in the hippocampus resemble those reported after persistent stress or long-term chronic glucocorticoid administration. The accompanying astrocytosis indicates a reactive, ongoing process. The findings suggest new therapeutic interventions in the treatment of paraphilia.