European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention-part 1

OBJECTIVE: The aim of this paper is to critically re-appraise the published trials assessing amitriptyline for migraine prophylaxis.

METHODS: We report our methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared amitriptyline with placebo for migraine prophylaxis in adults. Our outcomes of interest were informed by the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in migraine days per month, migraine days per month, and adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB 2.0 tool and the certainty of evidence by using the GRADE approach.

RESULTS: Our search yielded 10.826 unique records, of which three trials (n = 622) were eligible for data synthesis and analysis. We found moderate certainty evidence that amitriptyline increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo (relative risk: 1.60 (95% CI 1.17 to 2.19); absolute risk difference: 165 more per 1,000 (95% CI 47 more to 327 more). We found moderate certainty evidence that amitriptyline increases the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.05 (95% CI 0.01 to 0.10); absolute risk difference: 50 more per 1,000 (95% CI 10 more to 100 more).

CONCLUSIONS: Our meta-analysis showed that amitriptyline may have a prophylactic role in migraine patients, however these results are far from robust. This warrants further large-scale research to evaluate the role of amitriptyline in migraine prevention.