title: Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management.
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.
authors.affiliation: Division of Mood Disorders, Shanghai Hongkou District Mental Health Center, 159 Tongxin Road, Shanghai, 200083, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Psychology, Weifang Medical University, Shandong, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Sun
authors.affiliation: Division of Mood Disorders, Shanghai Hongkou District Mental Health Center, 159 Tongxin Road, Shanghai, 200083, China. wzwhk@163.com.
authors.forename: Zuowei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurology, Weifang Medical University Affiliated Hospital, Shandong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ren
authors.affiliation: 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.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.affiliation: 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. keming.gao@uhhospitals.org.
authors.forename: Keming
authors.initials: K
authors.lastname: Gao
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015994:Incidence; D001523:Mental Disorders / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012894:Sleep Stages / Q000187:drug effects*; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents