{
  "abstract": "Objectives Migraine headaches are common and potentially disabling disorders, with several interventions available for prevention and symptom reduction. We explored the comparative effectiveness and tolerability of pharmacological prophylaxis for migraine through a network meta-analysis of randomised trials (RCTs).Design Our study design was a systematic review and network meta-analysis (PROSPERO registration CRD42023456915).Eligibility criteria We included randomised controlled trials of prophylactic pharmacological interventions that enrolled adults diagnosed with chronic and/or episodic migraine headaches.Data sources Medline, Embase, Cochrane Central, PsycINFO, Web of Science and Scopus from inception to 15 January 2026.Risk of bias and certainty evidence Risk of bias was assessed using the modified Cochrane risk-of-bias tool 2.0 and the certainty evidence was evaluated by using the Grading of Recommendations Assessment, Development and Evaluation approach.Synthesis of results We performed a frequentist network meta-analysis using a random-effects model to compare the efficacy of interventions.Results We included 199 RCTs (47 420 participants). Overall, 29 trials (14.6%) were at low risk of bias; an adequate random allocation sequence generation was reported in 92 trials (46.2%), and missing outcome data was the most common limitation (110 trials, 55.3%). Compared with placebo, calcium channel blockers (mean difference (MD) −1.78 (95% CI −2.96 to −0.60), moderate certainty), calcitonin gene-related peptide (CGRP)-targeted therapies (MD −1.69 (95% CI −2.16 to −1.23), high certainty) and beta-blockers (MD −1.50 (95% CI −2.54 to −0.47), moderate certainty) were the most effective in reducing monthly migraine days. Moderate certainty evidence suggests beta-blockers (MD −1.31 (95% CI −1.76 to −0.85)), calcium channel blockers (MD −1.11 (95% CI −1.65 to −0.57)), anticonvulsants (MD −1.12 (95% CI −1.66 to −0.58)) and CGRP-targeted therapies (MD −0.76 (95% CI −1.49 to −0.02)) probably reduce monthly migraine attacks. However, moderate to high certainty evidence found that patients were more likely to discontinue calcium channel blockers (relative risk (RR) 1.40, 95% CI 1.04 to 1.88) and anticonvulsants (RR 1.14, 95% CI 1.01 to 1.29), compared with placebo.Conclusions When restricted to moderate or high certainty evidence, beta-blockers and CGRP-targeted therapies probably reduce migraine frequency and may be well-tolerated prophylactic options for migraine. Calcium channel blockers and anticonvulsants may also be effective for reducing migraine frequency but are less well tolerated by some patients.PROSPERO registration number CRD42023456915.",
  "authors": [
    {
      "affiliations": [
        "Michael G DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Malahat Khalili"
    },
    {
      "affiliations": [
        "The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia"
      ],
      "name": "Faraidoon Haghdoost"
    },
    {
      "affiliations": [
        "Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Isfahan, Iran"
      ],
      "name": "Amin Liaghatdar"
    },
    {
      "affiliations": [
        "Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Kian Torabiardakani"
    },
    {
      "affiliations": [
        "School of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran"
      ],
      "name": "Fatemeh Mahdian"
    },
    {
      "affiliations": [
        "Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Tal Levit"
    },
    {
      "affiliations": [
        "Michael G DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada",
        "Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Sara Moradi"
    },
    {
      "affiliations": [
        "École d’optométrie, Université de Montréal, Montreal, Quebec, Canada"
      ],
      "name": "Ehsan Hedayati"
    },
    {
      "affiliations": [
        "School of Dentistry, Islamic Azad University Shiraz, Shiraz, Fars, Iran"
      ],
      "name": "Farzaneh Ahmadi"
    },
    {
      "affiliations": [
        "Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Sahar Khademioore"
    },
    {
      "affiliations": [
        "Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Tariq Atkin-Jones"
    },
    {
      "affiliations": [
        "Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Vivek Patil"
    },
    {
      "affiliations": [
        "Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Fatemeh Mirzayeh Fashami"
    },
    {
      "affiliations": [
        "HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Kerman, Iran"
      ],
      "name": "Soheil Mehmandoost"
    },
    {
      "affiliations": [
        "Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada",
        "Michael G. DeGroote National Pain Centre, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Rachel J Couban"
    },
    {
      "affiliations": [
        "Department of Neurology, Fortis Hospital, Sector B1, Vasant Kunj, New Delhi, India"
      ],
      "name": "Kameshwar Prasad"
    },
    {
      "affiliations": [
        "Division of Neurology, University of Toronto, Toronto, Ontario, Canada",
        "Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Seyed-Mohammad Fereshtehnejad"
    },
    {
      "affiliations": [
        "Michael G DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Norman Buckley"
    },
    {
      "affiliations": [
        "Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada",
        "Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Jason W Busse"
    },
    {
      "affiliations": [
        "Michael G DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada",
        "Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada",
        "Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada"
      ],
      "name": "Behnam Sadeghirad"
    }
  ],
  "title": "Effectiveness and tolerability of pharmacological prophylaxis for migraine headaches: a systematic review and network meta-analysis of randomised controlled trials",
  "uid": "fcad9805-b8dd-5d05-a613-8d6fb2867894"
}