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Background  A large number patients struggle with migraine which is classified as a chronic disorder. The relative efficacy, safety and tolerability of prophylactic medications for migraine play a key role in managing this disease.    Methods  We conducted an extensive literature search for popular prophylactic medications that are used for migraine patients. Pairwise meta-analysis and network meta-analysis (NMA) were carried out sequentially for determining the relative efficacy, safety and tolerability of prophylactic medications. Summary effect for migraine headache days, headache frequency, at least 50% reduction in headache attacks, all-adverse events, nausea, somnolence, dizziness, withdrawal and withdrawal due to adverse events were produced by synthesizing both direct and indirect evidence.    Results  Patients with three interventions exhibited significantly less average migraine headache days compared with those treated by placebo (topiramate, propranolol, divalproex). Moreover, topiramate and valproate exhibited a significantly increased likelihood of at least 50% reduction in migraine headache attacks compared to placebo. Patients with topiramate and propranolol also exhibited significantly reduced headache frequency compared to those with placebo. On the other hand, patients with divalproex exhibited significantly higher risk of nausea compared to those with placebo, topiramate, propranolol, gabapentin and amitriptyline. Finally, divalproex was associated with an increased risk of withdrawal compared to placebo and propranolol.    Conclusions  Topiramate, propranolol and divalproex may be more efficacious than other prophylactic medications. Besides, the safety and tolerability of divalproex should be further verified by future studies.    Electronic supplementary material  The online version of this article (doi:10.1186/s10194-017-0720-7) contains supplementary material, which is available to authorized users.

Unveiling the relative efficacy, safety and tolerability of prophylactic medications for migraine: pairwise and network-meta analysis