TY - JOUR
T1 - Beneficial and harmful effects of tricyclic antidepressants for adults with major depressive disorder
T2 - a systematic review with meta-analysis and trial sequential analysis
AU - Kamp, Caroline Barkholt
AU - Petersen, Johanne Juul
AU - Faltermeier, Pascal
AU - Juul, Sophie
AU - Siddiqui, Faiza
AU - Barbateskovic, Marija
AU - Kristensen, Andreas Torp
AU - Moncrieff, Joanna
AU - Horowitz, Mark Abie
AU - Hengartner, Michael Pascal
AU - Kirsch, Irving
AU - Gluud, Christian
AU - Jakobsen, Janus Christian
N1 - © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.
PY - 2024/1/22
Y1 - 2024/1/22
N2 - 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.
AB - 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.
KW - Humans
KW - Antidepressive Agents, Tricyclic/adverse effects
KW - Depressive Disorder, Major/drug therapy
KW - Adult
KW - Quality of Life
KW - Randomized Controlled Trials as Topic
UR - http://www.scopus.com/inward/record.url?scp=85197852383&partnerID=8YFLogxK
U2 - 10.1136/bmjment-2023-300730
DO - 10.1136/bmjment-2023-300730
M3 - Review
C2 - 39093721
SN - 2755-9734
VL - 27
JO - BMJ mental health
JF - BMJ mental health
IS - 1
M1 - bmjment-2023-300730
ER -