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Psych Congress  

Sleep-Associated Adverse Events During Methylphenidate Treatment of Attention-Deficit/Hyperactivity Disorder in Youth: A Meta-Analysis


Stephen Faraone, PhD – Department of Psychiatry and Department of Neuroscience and Physiology, SUNY Upstate Medical University; Michelle Po, PhD – Highland Therapeutics Inc.; Marina Komolova, PhD – Highland Therapeutics Inc.; Samuele Cortese, MD – University of Southampton

Ironshore Pharmaceuticals & Development, Inc.

Purpose: Sleep disturbances are associated with attention-deficit/hyperactivity disorder (ADHD) and methylphenidate (MPH) treatment. We assessed whether sleep-related adverse event (AE) rates are affected by sample and study design features of trials evaluating MPH in youth with ADHD.

Methods: A meta-analysis was conducted on blinded placebo-controlled studies investigating MPH in youth with ADHD in naturalistic settings. Studies published in English were collected via online databases,, and the FDA website. Data extraction was conducted in duplicate with discrepancies resolved by discussion or by the senior investigator.

Results: Thirty-five studies yielding 75 observations of sleep-related AEs were included. Pooled relative risks (RRs) for sleep-related AEs were significantly increased with MPH treatment. After correcting for confounding sample or study design features, significant differences in mean RR of sleep-related AEs were identified among various MPH formulations. Given the wide range of differences in study methods that can affect absolute AE rates in both drug and placebo groups, their rates were found to be highly correlated (r=0.89; P < 0.0001). Observed placebo rates of sleep-related AEs closely predicted the observed RR of sleep-related AEs, with higher placebo rates associated with a lower RR. This enables the prediction of the expected RR based solely on the observed placebo AE rate.

Conclusion: Sleep-related AEs were associated with MPH and certain study design and sample features significantly influenced RR. By demonstrating that RR and its interpretation are significantly constrained by the placebo sleep-related AE rate, we provide the field with a useful covariate for adjusting RR statistics.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.

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