A recent 3-month double-blind, placebo-controlled study demonstrated efficacy and safety of pediatric prolonged-release melatonin (PedPRM) for insomnia in children with autism spectrum disorder. This study examined the long-term effects of PedPRM treatment on sleep, growth, body mass index, and pubertal development. Eighty children and adolescents (2-17.5 years of age; 96% with autism spectrum disorder) who completed the double-blind, placebo-controlled trial were given 2 mg, 5 mg, or 10 mg PedPRM nightly up to 104 weeks, followed by a 2-week placebo period to assess withdrawal effects. Improvements in child sleep disturbance and caregiver satisfaction with child sleep patterns, quality of sleep, and quality of life were maintained throughout the 104-week treatment period (p < .001 versus baseline for all). During the 2-week withdrawal placebo period, measures declined compared with the treatment period but were still improved compared with baseline. PedPRM was generally safe; the most frequent treatment-related adverse events were fatigue (6.3%), somnolence (6.3%), and mood swings (4.2%). Changes in mean weight, height, body mass index, and pubertal status (Tanner staging done by a physician) were within normal ranges for age with no evidence of delay in body mass index or pubertal development. Nightly PedPRM at optimal dose (2, 5, or 10 mg nightly) is safe and effective for long-term treatment in children and adolescents with autism spectrum disorder and insomnia. There were no observed detrimental effects on children's growth and pubertal development and no withdrawal or safety issues related to the use or discontinuation of the drug. Efficacy and Safety of Circadin in the Treatment of Sleep Disturbances in Children With Neurodevelopment Disabilities; https://clinicaltrials.gov/; NCT01906866.

BACKGROUND: Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolar I disorder (BP-I) are lacking. METHODS: This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7–17 years) with BP-I/manic or mixed episodes compared lithium (n = 53) versus placebo (n = 28) for up to 8 weeks. The a priori primary efficacy measure was change from baseline to the end of study (week 8/ET) in the Young Mania Rating Scale (YMRS) score, based on last-observation-carried-forward analysis. RESULTS: The change in YMRS score was significantly larger in lithium-treated participants (5.51 [95% confidence interval: 0.51 to 10.50]) after adjustment for baseline YMRS score, age group, weight group, gender, and study site (P = .03). Overall Clinical Global Impression–Improvement scores favored lithium (n = 25; 47% very much/much improved) compared with placebo (n = 6; 21% very much/much improved) at week 8/ET (P = .03). A statistically significant increase in thyrotropin concentration was seen with lithium (3.0 ± 3.1 mIU/L) compared with placebo (–0.1 ± 0.9 mIU/L; P < .001). There was no statistically significant between-group difference with respect to weight gain. CONCLUSIONS: Lithium was superior to placebo in reducing manic symptoms in pediatric patients treated for BP-I in this clinical trial. Lithium was generally well tolerated in this patient population and was not associated with weight gain, distinguishing it from other agents commonly used to treat youth with bipolar disorder.

To evaluate the efficacy and safety of aripiprazole versus placebo in preventing relapse of irritability symptoms associated with autistic disorder in pediatric patients. This multicenter, double-blind, randomized, placebo-controlled, relapse-prevention trial enrolled patients (6-17 years) who met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DMS-IV-TR) criteria for autistic disorder and who also had serious behavioral problems (ie, tantrums, aggression, self-injurious behavior, or a combination of these behavioral problems) between March 2011 and June 2012. In phase 1, single-blind aripiprazole was flexibly dosed (2-15 mg/d) for 13-26 weeks. Patients with a stable response (≥ 25% decrease in Aberrant Behavior Checklist-irritability subscale score and a rating of "much improved" or "very much improved" on the Clinical Global Impressions-Improvement scale) for 12 consecutive weeks were randomized into phase 2 to continue aripiprazole or switch to placebo. Treatment was continued until relapse or up to 16 weeks. The primary end point was time from randomization to relapse. Eighty-five patients were randomized in phase 2. The difference in time to relapse between aripiprazole and placebo was not statistically significant (P = .097). Kaplan-Meier relapse rates at week 16 were 35% for aripiprazole and 52% for placebo (hazard ratio [HR] = 0.57; number needed to treat [NNT] = 6). The most common adverse events during phase 1 were weight increase (25.2%), somnolence (14.8%), and vomiting (14.2%); and, during phase 2 (aripiprazole vs placebo), they were upper respiratory tract infection (10.3% vs 2.3%), constipation (5.1% vs 0%), and movement disorder (5.1% vs 0%). In this study, there was no statistically significant difference between aripiprazole and placebo in time to relapse during maintenance therapy. However, the HR and NNT suggest some patients will benefit from maintenance treatment. Patients receiving aripiprazole should be periodically reassessed to determine the continued need for treatment. ClinicalTrials.gov identifier: NCT01227668.

Quetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania. Large, placebo-controlled studies of interventions in pediatric bipolar depression are lacking. The current study investigated the efficacy and safety of quetiapine extended-release (XR) in patients 10-17 years of age, with acute bipolar depression. This multicenter, double-blind, randomized, placebo-controlled study investigated quetiapine XR (dose range, 150-300 mg/day) in pediatric outpatients with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I or bipolar II disorder (current or most recent episode depressed) treated for up to 8 weeks (ClinicalTrials.gov identifier: NCT00811473). The primary study outcome was mean change in Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary efficacy outcomes included CDRS-R-based response and remission rates. Of 193 patients randomized to treatment, 144 patients completed the study (75.3% of quetiapine XR group [n=70]; 74.0% of placebo group [n=74]). Least squares mean changes in CDRS-R total score at week 8 were: -29.6 (SE, 1.65) with quetiapine XR and -27.3 (SE, 1.60) with placebo, a between-treatment group difference of -2.29 (SE, 1.99; 95% CI, -6.22, 1.65; p=0.25; mixed-model for repeated measures analysis). Rates of response and remission did not differ significantly between treatment groups. The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release (IR). Potentially clinically significant elevations in clinical chemistry values included triglycerides (9.3%, quetiapine XR; 1.4%, placebo group) and thyroid stimulating hormone (4.7%, quetiapine XR; 0%, placebo group). An adverse event potentially related to diabetes mellitus occurred in 3.3% of the quetiapine XR versus no adverse events in the placebo group. Quetiapine XR did not demonstrate efficacy relative to placebo in this 8 week study of pediatric bipolar depression. Quetiapine XR was generally safe and well tolerated.