PEDIATRICS Vol. 123 No. 5 May 2009, pp. e770-e776 (doi:10.1542/peds.2008-2945)
ARTICLE |
Controlled Clinical Trial of Zolpidem for the Treatment of Insomnia Associated With Attention-Deficit/ Hyperactivity Disorder in Children 6 to 17 Years of Age
a Division of Pediatric Pharmacology/Critical Care, Rainbow Babies and Children's Hospital
b Division of Child and Adolescent Psychiatry, University Hospitals, Case Medical Center, Cleveland, Ohio
c Department of Biostatistics, School of Public Health, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey
d Department of Clinical Development, sanofi-aventis, Chilly-Mazarin, France
e Department of Clinical Pharmacology and Toxicology, Children's Hospital Medical Center of Akron, Akron, Ohio
OBJECTIVE. The goal was to evaluate the hypnotic efficacy of zolpidem at 0.25 mg/kg per day (maximum of 10 mg/day), compared with placebo, in children 6 through 17 years of age who were experiencing insomnia associated with attention-deficit/hyperactivity disorder.
METHODS. An 8-week, North American, multicenter, double-blind, placebo-controlled, parallel-group study was conducted. Patients underwent stratification according to age (6–11 years [N = 111] or 12–17 years [N = 90]) and were assigned randomly to receive treatment with the study drug or placebo (in a 2:1 ratio). The primary efficacy variable was latency to persistent sleep between weeks 3 and 6. Secondary efficacy variables also were assessed, and behavioral and cognitive components of attention-deficit/hyperactivity disorder were monitored. Safety was assessed on the basis of reports of adverse events, abnormal laboratory data, vital signs, and physical examination findings. The potential for next-day residual effects also was assessed.
RESULTS. The baseline-adjusted mean change in latency to persistent sleep at week 4 did not differ significantly between the zolpidem and placebo groups (–20.28 vs –21.27 minutes). However, differences favoring zolpidem were observed for the older age group in Clinical Global Impression scores at weeks 4 and 8. No next-day residual effects of treatment were associated with zolpidem, and no rebound phenomena occurred after treatment discontinuation. Central nervous system and psychiatric disorders were the most-frequent treatment-emergent adverse events (>5%) that were observed more frequently with zolpidem than with placebo; these included dizziness, headache, and hallucinations. Ten (7.4%) patients discontinued zolpidem treatment because of adverse events.
CONCLUSION. Zolpidem at a dose of 0.25 mg/kg per day to a maximum of 10 mg failed to reduce the latency to persistent sleep on polysomnographic recordings after 4 weeks of treatment in children and adolescents 6 through 17 years of age who had attention-deficit/hyperactivity disorder-associated insomnia.
Key Words: insomnia • attention-deficit/hyperactivity disorder • zolpidem • latency to persistent sleep
Abbreviations: ADHD—attention-deficit/hyperactivity disorder • AE—adverse event • CGI—Clinical Global Impression • CGI-I—Clinical Global Impression-Improvement • CGI-S—Clinical Global Impression-Severity • CI—confidence interval • CPT-II—Continuous Performance Test II • IP—investigational product • LPS—latency to persistent sleep • LS—least-squares • NAASO—number of awakenings after sleep onset • TST—total sleep time • WASO—wake time after sleep onset
Accepted Jan 12, 2009.
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