Systematic Review and Meta-Analysis: The Association Between Newer-Generation Antidepressants and Insomnia in Children and Adolescents With Major Depressive Disorder
Türkmen, Cagdas Machunze, Noah Lee, Alycia M Bougelet, Emilie Ludin, Nicola M de Cates, Angharad N Vollstädt-Klein, Sabine Bach, Patrick Kiefer, Falk Burdzovic Andreas, Jasmina
Türkmen, Cagdas
Machunze, Noah
Lee, Alycia M
Bougelet, Emilie
Ludin, Nicola M
de Cates, Angharad N
Vollstädt-Klein, Sabine
Bach, Patrick
Kiefer, Falk
Burdzovic Andreas, Jasmina
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Affiliation
University of Heidelberg; University of Auckland; University of Oxford; Coventry and Warwickshire NHS Partnership Trust; German Center for Mental Health (DZPG); Norwegian Institute of Public Health; University of Oslo; University Medical Center Groningen; University of Texas Southwestern Medical Center, Dallas; Children's Medical Center, Dallas; Maastricht University
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Publication date
2025-01
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Abstract
Objective: To examine the association between newer generation antidepressants and insomnia as an adverse event (AE) in the treatment of children and adolescents with major depressive disorder (MDD).
Method: A systematic search was performed in major databases (inception to August 31, 2023) to retrieve double-blind, placebo-controlled, randomized controlled trials (RCTs) evaluating the safety of 19 antidepressants in the acute treatment (initial 6-12 weeks) of children and adolescents ≤18 years of age with MDD (primary analyses). RCTs in anxiety disorders and obsessive-compulsive disorder (OCD) were retrieved from a recent meta-analysis and included in complementary analyses. A mixed-effects logistic regression model was used to compare the frequency of insomnia in the antidepressant relative to the placebo group. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool.
Results: In total, 20 trials in MDD (N = 5,357) and 8 trials in anxiety disorders and OCD (N = 1,271) evaluating selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) were included. In MDD, antidepressant treatment was associated with a modest increase in the odds of insomnia compared with placebo (odds ratio [OR] = 1.65, 95% CI = 1.21-2.27, p = .002), with no significant difference between SSRIs and SNRIs. The RCTs showed low risk of bias or minor concerns for the assessment of insomnia. The odds of treatment-emergent insomnia were significantly lower in MDD (OR = 1.62; 95% CI = 1.21-2.15) compared to anxiety disorders and OCD (OR = 2.89; 95% CI = 1.83-4.57) for treatment with SSRIs (p = .03). Among individual antidepressants with evidence from ≥3 studies, sertraline had the highest OR (3.45; 95% CI = 1.91-6.24), whereas duloxetine had the lowest OR (1.38; 95% CI = 0.79-2.43).
Conclusion: Children and adolescents are at a modestly increased risk for experiencing insomnia during the first 6 to 12 weeks of treatment with SSRIs and SNRIs. Antidepressant- and disorder-specific variability in the risk of treatment-emergent insomnia may be relevant to consider in clinical decision making.
Study preregistration information: The association between newer generation antidepressants and insomnia in children and adolescents with major depressive disorder: a meta-analysis of randomized controlled trials; https://www.crd.york.ac.uk; CRD42023330506.
Citation
Türkmen C, Machunze N, Lee AM, Bougelet E, Ludin NM, de Cates AN, Vollstädt-Klein S, Bach P, Kiefer F, Burdzovic Andreas J, Kamphuis J, Schoevers RA, Emslie GJ, Hetrick SE, Viechtbauer W, van Dalfsen JH. Systematic Review and Meta-Analysis: The Association Between Newer-Generation Antidepressants and Insomnia in Children and Adolescents With Major Depressive Disorder. J Am Acad Child Adolesc Psychiatry. 2025 Jan 17:S0890-8567(25)00013-9. doi: 10.1016/j.jaac.2025.01.006. Epub ahead of print. PMID: 39828036.
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Article