A Randomized, Double-Blind, Placebo-Controlled Study of HLD200, a Delayed-Release and Extended-Release Methylphenidate, in Children with Attention-Deficit/Hyperactivity Disorder: An Evaluation of Safety and Efficacy Throughout the Day and Across Settings.

Objectives: HLD200, a once-daily, evening-dosed, delayed-release and extended-release methylphenidate (DR/ER-MPH), was designed to provide therapeutic effect beginning upon awakening and lasting into the evening. This pivotal, randomized, double-blind, multicenter, placebo-controlled, phase 3 trial assessed improvements in functional impairment across the day using multiple validated measures tailored for different settings and time of day in children (6-12 years) with attention-deficit/hyperactivity disorder (ADHD). Methods: Following a 6-week, open-label titration of DR/ER-MPH to an optimal dose (20, 40, 60, 80, or 100 mg/day) and dosing time (8:00 PM ±1.5 hours), participants were randomized to treatment-optimized DR/ER-MPH or placebo for 1 week. The primary endpoint was the model-adjusted average of postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale combined scores (SKAMP CS) over a 12-hour laboratory classroom day (8:00 AM to 8:00 PM). The key secondary endpoint was the Parent Rating of Evening and Morning Behavior-Revised, Morning (PREMB-R AM) subscale. Secondary/exploratory measures included the PREMB-R Evening (PREMB-R PM) subscale and Permanent Product Measure of Performance (Attempted [PERMP-A] and Correct [PERMP-C]). Safety endpoints included treatment-emergent adverse events (TEAEs). Results: After the treatment-optimization phase, the mean optimized dose was 66.2 mg and the most common prescribed dosing time was 8:00 PM. Double-blind DR/ER-MPH treatment significantly improved functional impairment versus placebo in the early morning (PREMB-R AM: p < 0.001), averaged over the classroom day (SKAMP CS: p < 0.001), and in the late afternoon/evening (PREMB-R PM: p = 0.003) in the intent-to-treat population (N = 117). Average PERMP-A (p = 0.006) and PERMP-C (p = 0.009) also indicated improved classroom performance with DR/ER-MPH versus placebo. In the double-blind phase, TEAEs did not differ between DR/ER-MPH and placebo groups and no serious TEAEs or TEAEs leading to discontinuation were reported. Conclusion: DR/ER-MPH was well tolerated and demonstrated significant improvements versus placebo in functional impairment throughout the day across different settings in children with ADHD.

Reliability and Validity of the Daily Parent Rating of Evening and Morning Behavior Scale, Revised.

OBJECTIVE: Children with ADHD frequently manifest behavioral difficulties in the morning prior to school. We sought to assess the reliability and validity of the Daily Parent Rating of Evening and Morning Behavior Scale, Revised (DPREMB-R) morning score as a measure of morning behaviors impaired by ADHD. METHOD: We used data from a clinical trial of HLD200 treatment in pediatric participants with ADHD to address our objectives. RESULTS: The DPREMB-R morning score showed significant internal homogeneity, test-retest reliability ( r = .52-.45), and good concurrent validity ( r = .50-.71). CONCLUSION: The DPREMB-R morning score could be a useful instrument for assessing treatment efficacy in the morning before school.

Aripiprazole in the treatment of pediatric bipolar disorder: a systematic chart review.

BACKGROUND: Pediatric bipolar disorder is a serious neuropsychiatric disorder associated with high levels of morbidity and disability. OBJECTIVE: This is a systematic chart review of all outpatient youth with the diagnosis of bipolar disorder and bipolar spectrum disorder treated with aripiprazole either alone or as add-on to ongoing treatments. METHOD: Medical records were reviewed to identify all subjects with bipolar and bipolar spectrum disorder prescribed aripiprazole in our clinic. During the chart review, the Clinical Global Impression scale was completed by the treating clinicians to determine usefulness. RESULTS: Forty-one youths (mean age+/-SD: 11.4+/-3.5 years) with bipolar spectrum disorder who had been treated with aripiprazole were identified. These children received a mean daily dose of aripiprazole 16.0+/-7.9 mg over an average of 4.6 months. Using a Clinical Global Impression-Improvement scale score of <2 (very much/much improved) to define robust improvement, 71% showed improvement in manic symptoms. Treatment with aripiprazole was well tolerated. CONCLUSION: This study suggests that aripiprazole may be a useful and well-tolerated treatment for youth with bipolar disorder and it supports the need for controlled clinical trials of this compound in juvenile mania.

Prevalence of psychopathology in preschool-age children.

PROBLEM: Little is known about psychopathology in preschool-age children. METHODS: A review of representative studies of psychiatric disorders in preschoolers. FINDINGS: Sample sizes ranged from 104 to 3,860 subjects, ages 1 to 9 years. Prevalence rates of psychiatric disorders varied from 0.1% to 26.4%; high rates of co-morbidity were reported. CONCLUSIONS: Studies addressing psychiatric disorders in preschoolers are extremely limited. Future research is needed to improve the diagnosis, treatment, and outcomes in preschool-age children.