Adverse effects of 21 antidepressants on sleep during acute-phase treatment in major depressive disorder: a systemic review and dose-effect network meta-analysis

Shuzhe Zhou; Pei Li; Xiaozhen Lv; Xuefeng Lai; Zuoxiang Liu; Junwen Zhou; Fengqi Liu; Yiming Tao; Meng Zhang; Xin Yu; Jingwei Tian; Feng Sun

doi:10.1093/sleep/zsad177

Adverse effects of 21 antidepressants on sleep during acute-phase treatment in major depressive disorder: a systemic review and dose-effect network meta-analysis

Sleep. 2023 Oct 11;46(10):zsad177. doi: 10.1093/sleep/zsad177.

Authors

Shuzhe Zhou^{1

2}, Pei Li³, Xiaozhen Lv^{1

2}, Xuefeng Lai³, Zuoxiang Liu³, Junwen Zhou³, Fengqi Liu³, Yiming Tao³, Meng Zhang³, Xin Yu^{1

2}, Jingwei Tian⁴, Feng Sun^{3

5}

Affiliations

¹ Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China.
² NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
³ Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
⁴ School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China.
⁵ Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China.

Abstract

Study objectives: Sleep-related adverse effects during acute treatment with antidepressants undermine adherence and impede remission. We aimed to address subtypes of sleep-related adverse effects and depict the relationship between dose and sleep-related adverse events.

Methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science for double-blind randomized controlled trials of depression published before April 30th, 2023. Eligible studies reporting sleep-related adverse effects during short-term monotherapy were included. The odds ratios (ORs) for sleep-related adverse effects were addressed with network meta-analysis. A Bayesian approach was used to depict the dose-effect relationship. Heterogeneity among studies was assessed using the τ2 and I2 statistics. Sensitivity analyses were performed without studies featuring high risk of bias.

Results: Studies with 64 696 patients were examined from 216 trials. Compared to placebo, 13 antidepressants showed higher ORs for somnolence, of which fluvoxamine (OR = 6.32; 95% CI: 3.56 to 11.21) ranked the top. Eleven had higher risks for insomnia, reboxetine ranked the top (OR = 3.47; 95% CI: 2.77 to 4.36). The dose-effect relationships curves between somnolence or insomnia and dose included linear shape, inverted U-shape, and other shapes. There was no significant heterogeneity among individual studies. The quality of evidence for results in network meta-analyses was rated as very low to moderate by Grading of Recommendations Assessment, Development, and Evaluation.

Conclusions: Most antidepressants had higher risks for insomnia or somnolence than placebo. The diverse relationship curves between somnolence or insomnia and dose of antidepressants can guide clinicians to adjust the doses. These findings suggest clinicians pay more attention to sleep-related adverse effects during acute treatment with antidepressants.

Keywords: adverse effects; antidepressants; insomnia; major depressive disorders; somnolence.

Abstract

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