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Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management

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Abstract

Somnolence is a common side effect of antipsychotics. To assess the incidence of this side effect, we performed a MEDLINE search for randomized, double-blinded, placebo- or active-controlled studies of adult patients treated with antipsychotics for schizophrenia, mania, bipolar depression, or bipolar disorder. We extracted rates of somnolence from original publications and pooled them based on the dose of each antipsychotic in the same psychiatric condition, then estimated the absolute risk increase (ARI) and the number needed to harm (NNH) of an antipsychotic relative to placebo or an active comparator in the same psychiatric condition. According to the ARI in acute schizophrenia, bipolar mania, and bipolar depression, antipsychotics can be classified as high somnolence (clozapine), moderate somnolence (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone), and low somnolence (aripiprazole, asenapine, haloperidol, lurasidone, paliperidone, cariprazine). The risk of somnolence with blonanserin, brexpiprazole, chlorpromazine, iloperidone, sertindole, and zotepine needs further investigation. The rates of somnolence were positively correlated to dose and duration for some antipsychotics, but not for others. Many factors, including antipsychotic per se, the method used to measure somnolence, patient population, study design, and dosing schedule, might affect the incidence of antipsychotic-induced somnolence. The mechanisms of antipsychotic-induced somnolence are likely multifactorial, although the blockade of histamine 1 receptors and α1 receptors may play a major role. The management of antipsychotic-induced somnolence should include sleep hygiene education, choosing an antipsychotic with a lower risk for somnolence, starting at a lower dose with a slower titration based on psychiatric diagnoses, adjusting doses when necessary, and minimizing concurrent somnolence-prone agents. Since most cases of somnolence were mild to moderate, allowing tolerance to develop over at least 4 weeks is reasonable before discontinuing an antipsychotic.

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Acknowledgments

The authors express their gratitude to Mrs. Mary Beth Serrano, MA, a research manager in the Mood Disorders Program of University Hospitals Case Medical Center/Case Western Reserve University for her proofreading of the manuscript.

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    Authors and Affiliations

    1. Division of Mood Disorders, Shanghai Hongkou District Mental Health Center, 159 Tongxin Road, Shanghai, 200083, China

      Fang Fang & Zuowei Wang

    2. Department of Psychology, Weifang Medical University, Shandong, China

      Hongwei Sun

    3. Department of Neurology, Weifang Medical University Affiliated Hospital, Shandong, China

      Ming Ren

    4. Mood and Anxiety Clinic in the Mood Disorders Program of University Hospitals Case Medical Center/Case Western University School of Medicine, 10524 Euclid Avenue, 12th floor, Cleveland, OH, 44106, USA

      Joseph R. Calabrese & Keming Gao

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    Correspondence to Zuowei Wang or Keming Gao.

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    Conflict of interest

    Dr. Calabrese has received lecture honoraria thorough speaking engagements from AstraZeneca, Benecke, CME Outfitters, Dainippon Sumitomo Pharma, Elan, Forest, Health & Wellness Partners, Lundbeck, Medwiz, Otsuka, ProMedica, Spirant Communication Private Limited, Sunovion, Takeda, Teva, and Wenckebach Institute, American Foundation Suicide Prevention, University of Florida, and Western Psychiatric Institute. He has acted as consultant to Biomedical Development Corporation, Convergent Health Solutions, Dainippon Sumitomo Pharma, Elan, Forest, Health and Wellness Partners, Lilly, Lundbeck, Otsuka, Scientia, Takeda, and Teva. He has received research support from the US National Institutes of Health (NIH). Dr. Gao has received grant support from AstraZeneca, the Brain and Behavior Research Foundation, and the Cleveland Foundation and has been on a speakers’ bureau for Sunovion. Dr. Wang has received grant support from the National Natural Science Foundation of China (grant number 81301159); Shanghai Key Medicine Specialties Program (grant number ZK2012A12); and the Training Plan for Excellent Academic Leaders of Shanghai Health System (grant number XBR2013087). Drs. Fang, Sun, and Ren have no conflicts of interest to disclose.

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    F. Fang and H. Sun contributed equally.

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    Fang, F., Sun, H., Wang, Z. et al. Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management. CNS Drugs 30, 845–867 (2016). https://doi.org/10.1007/s40263-016-0352-5

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