Comparative Efficacy and Safety of Tricyclic Antidepressants (TCAs) Versus Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) for Migraine Prophylaxis: A Systematic Review and Meta-Analysis
Sufyan Shahid1, Abdullah Farooq2, Ayesha Batool3, Umna N/A4, Syed Ali4, Humza Saeed5, Megha Joshi6, Advait Teli7, Japleen Kaur8
1Khawaja Muhammad Safdar Medical College, Sialkot, Pakistan, 2Lahore Medical and Dental College, Lahore, 3Allama Iqbal Medical College, Lahore, Pakistan, 4Jinnah Sindh Medical University, Karachi, 5Rawalpindi Medical University, Rawalpindi, Pakistan, 6Essen Health Care, New York, 7Bharati Vidyapeeth Deemed University and Medical College Pune, India, 8Department of Neurosciences, University of California, San Diego
Objective:
We performed a systematic review and meta-analysis to evaluate the comparative efficacy and safety of TCAs versus SNRIs for migraine prophylaxis.
Background:
Migraine is a leading cause of global disability, yet research on prophylactic interventions remains limited due to unclear underlying mechanisms. Recent trials comparing SNRIs and TCAs provide new hope for advancing prophylactic interventions, but data remain limited.
Design/Methods:
PubMed, Embase, Scopus, and Cochrane Central databases were searched to identify randomized controlled trials (RCTs) involving migraine patients and comparing SNRIs with TCAs. We applied a random effects model and pooled risk ratios (RRs) along with 95% confidence interval (CI) using RevMan 5.4. Quality assessment was performed using the Rob 2 tool.
Results:
Three RCTs involving 333 patients (mean age 32.4 years, 68% female) with a mean follow-up of 10 weeks were included in the analysis. Migraine frequency (attacks per month) was comparable between the SNRI and TCA groups (MD = -0.03, 95% CI: -0.67 to 0.61; p = 0.93). However, patients receiving TCAs experienced slightly longer migraine attack durations compared to those on SNRIs (MD = 0.71, 95% CI: 0.01 to 1.41; p = 0.05). Additionally, adverse events were significantly fewer in the SNRI group than TCA group (RR = 1.47, 95% CI: 1.10 to 1.97; p = 0.009). All trials were rates as low risk.
Conclusions:
SNRIs demonstrated comparable efficacy to TCAs in reducing migraine frequency, with shorter attack duration and fewer adverse events.
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