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. 2023 Oct 11;46(10):zsad177.
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

Shuzhe Zhou  1   2 , Pei Li  3 , Xiaozhen Lv  1   2 , Xuefeng Lai  3 , Zuoxiang Liu  3 , Junwen Zhou  3 , Fengqi Liu  3 , Yiming Tao  3 , Meng Zhang  3 , Xin Yu  1   2 , Jingwei Tian  4 , Feng Sun  3   5
Affiliations

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 et al. Sleep. .

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.

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Figures

Figure 1.
Figure 1.
The flow diagram for study selection.
Figure 2.
Figure 2.
The result of risk of bias assessment.
Figure 3.
Figure 3.
The network of evidence for main outcomes: (A) Somnolence; (B) Insomnia. The size of the nodes represents the sample size of each treatment group, and the width of the lines connecting different nodes is proportional to the number of RCTs comparing every pair of treatments.
Figure 4.
Figure 4.
Forest plot displaying the result of network meta-analysis for main outcomes. (A) Somnolence; (B) Insomnia.
Figure 5.
Figure 5.
Dose-effect relationship of each drug between dose and sleep-related adverse events. (A) somnolence; (B) insomnia; Y-axis represents the absolute risk for somnolence or insomnia of different doses of antidepressants. X-axis represents doses of antidepressants, 0 represents placebo.
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References

    1. Mathers CD, Loncar D.. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3:e442. doi: 10.1371/journal.pmed.0030442 - DOI - PMC - PubMed
    1. Kennedy SH, Lam RW, Mcintyre RS, et al.; Canadian Network for Mood and Anxiety Treatments (CANMAT). Clinical guidelines for the management of adults with major depressive disorder. Can J Psychiatry. 20162016;61:540–560. doi: 10.1177/0706743716659417 - DOI - PMC - PubMed
    1. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391:1357–1366. doi: 10.1016/S0140-6736(17)32802-7 - DOI - PMC - PubMed
    1. Reichenpfader U, Gartlehner G, Morgan LC, et al. Sexual dysfunction associated with second-generation antidepressants in patients with major depressive disorder: results from a systematic review with network meta-analysis. Drug Saf. 2014;37:19–31. doi: 10.1007/s40264-013-0129-4 - DOI - PubMed
    1. Oliva V, Lippi M, Paci R, et al. Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: a systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2021;109:110266. doi: 10.1016/j.pnpbp.2021.110266 - DOI - PubMed