Most antidepressants have a higher risk for somnolence and insomnia compared with placebo, according to study findings published in the journal Sleep.
Sleep-related adverse events have previously been reported in patients taking antidepressants. Researchers conducted a study to assess the association between sleep-related adverse effects and antidepressant dosage.
The researchers included double-blind, randomized control trials from PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science in the analysis. All studies assessed the sleep-related adverse effects of certain antidepressants.
The inclusion criteria for studies were adult patient aged 18 years and older with a diagnosis of major depressive disorder (MDD). These studies compared antidepressants with either placebo, different antidepressants, or different doses of antidepressants.
Exclusion criteria are studies that have patients with postpartum depression, post-stroke depression, concomitant illnesses, and studies with more than 20% of the patient population being diagnosed with bipolar or psychotic depression. The primary outcomes were insomnia and somnolence.
Of the 999 studies reviewed, 216 were included in this study, with 163 included in the meta-analyses for somnolence and 166 included in the meta-analyses for insomnia. There were 64,696 patient records extracted from these studies.
The average age of study participants was 45.5 years and 63.2% were women. A total of 127 (58.8%) studies used placebo control individuals and 45 (20.8%) studies included a group treated with paroxetine.
A majority (85; 39.4%) of studies were conducted in North America, 58 (26.9%) were conducted in Europe, 20 (9.7%) were from Asia, and 32 (14.8%) were carried out across multiple continents.
Across the 163 studies in the somnolence analysis, there was a 4.5% prevalence of somnolence reported. When compared with the placebo group, there were 13 antidepressants with higher odds ratios (OR) for somnolence, with fluvoxamine reporting the highest OR of 6.32 (95% CI, 3.56-11.21). The researchers reported lower OR for somnolence in bupropion (OR, 0.50; 95% CI, 0.30-0.82) when compared with placebo.
Of the 166 studies assessing insomnia, the prevalence was approximately 5.4%. When compared with the placebo group, 11 antidepressant medications had higher insomnia risks, with reboxetine reporting the highest OR of 3.47 (95% CI, 2.77-4.36). The researchers found that compared with placebo, amitriptyline (OR, 0.63; 95% CI, 0.42-0.92) was associated with a lower insomnia risk.
The quality of evidence for the results was reported as very low to moderate according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment.
“The diverse relationship curves between somnolence or insomnia and dose of antidepressants can guide clinicians to adjust the doses,” the researchers wrote. “These findings suggest clinicians pay more attention to sleep-related adverse effects during acute treatment with antidepressants.”
Study limitations are the exclusion of patients with postpartum and post-stroke depression, the lack of analysis on other sleep disorders, and somnolence and insomnia not being the primary or secondary endpoint in most studies.
Zhou S, Li P, Lv X, et al. 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. Published online July 9, 2023. doi:10.1093/sleep/zsad177