Beneficial and harmful effects of tricyclic antidepressants for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis
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Authors
Kamp, Caroline Barkholt
Petersen, Johanne Juul
Faltermeier, Pascal
Juul, Sophie
Siddiqui, Faiza
Barbateskovic, Marija
Kristensen, Andreas Torp
Moncrieff, Joanna
Horowitz, Mark
Hengartner, Michael P.
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Issue Date
22/01/2024
Type
Journal article
Language
Keywords
Mental Health
Alternative Title
Abstract
Question
Tricyclic antidepressants are used to treat depression worldwide, but the adverse effects have not been systematically assessed. Our objective was to assess the beneficial and harmful effects of all tricyclic antidepressants for adults with major depressive disorder. Study selection and analysis We conducted a systematic review with meta-analysis and trial sequential analysis. We searched CENTRAL, MEDLINE, Embase, LILACS and other sources from inception to January 2023 for randomised clinical trials comparing tricyclic antidepressants versus placebo or 'active placebo' for adults with major depressive disorder. The primary outcomes were depressive symptoms measured on the 17-item Hamilton Depression Rating Scale (HDRS-17), serious adverse events and quality of life. The minimal important difference was defined as three points on the HDRS-17. Findings We included 103 trials randomising 10 590 participants. All results were at high risk of bias, and the certainty of the evidence was very low or low. All trials only assessed outcomes at the end of the treatment period at a maximum of 12 weeks after randomisation. Meta-analysis and trial sequential analysis showed evidence of a beneficial effect of tricyclic antidepressants compared with placebo (mean difference −3.77 HDRS-17 points; 95% CI −5.91 to −1.63; 17 trials). Meta-analysis showed evidence of a harmful effect of tricyclic antidepressants compared with placebo on serious adverse events (OR 2.78; 95% CI 2.18 to 3.55; 35 trials), but the required information size was not reached. Only 2 out of 103 trials reported on quality of life and t-tests showed no evidence of a difference.
Conclusions
The long-term effects of tricyclic antidepressants and the effects on quality of life are unknown. Short-term results suggest that tricyclic antidepressants may reduce depressive symptoms while also increasing the risks of serious adverse events, but these results were based on low and very low certainty evidence. PROSPERO registration number CRD42021226161.
Description
Citation
BMJ Mental Health. 2024;27:e300730. https://doi.org/10.1136/bmjment-2023-300730
Publisher
License
Journal
BMJ Mental Health
Volume
27
Issue
1