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

The Journal of Headache and Pain, Feb 2017

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.

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

He et al. The Journal of Headache and Pain Unveiling the relative efficacy, safety and tolerability of prophylactic medications for migraine: pairwise and network-meta analysis Aijie He 3 Dehua Song 2 Lei Zhang 1 Chen Li 0 0 Department of Anesthesia, Yantai Hospital of Traditional Chinese Medicine , No. 39 Xingfu Road, Zhifu Disctrict, 264000 Yantai, Shandong , China 1 Department of Pharmacy, Yantai Hospital of Traditional Chinese Medicine , 264000 Yantai, Shandong , China 2 Department of Radiotherapy, the Affiliated Yantai Yuhuangding Hospital of Qingdao University , 264000 Yantai, Shandong , China 3 Department of Neurosurgery, the Affiliated Yantai Yuhuangding Hospital of Qingdao University , 264000 Yantai, Shandong , China 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. Migraine; Efficacy; Safety; Tolerability; Network meta-analysis - Background Migraine is a chronic neurological disorder with high prevalence. Females appeared to have a higher morbidity of migraine than males in developed countries [1]. Although a relatively small number of migraine cases were reported in Asia, the morbidity of migraine attack in this region can reach up to 9.3% [2]. Throbbing headache is usually accompanied with migraine, resulting in both poor productivity and unstable emotional state [3, 4]. Migraine patients are often managed by medications which are convenient and efficient. However, side effects such as nausea and dizziness resulted from these medications have been observed in patients who exhibited poor level of tolerance [5]. Two types of medications have been introduced to patients: abortive and preventative medications [6]. The above two types of medications differ considerably in their mechanisms: abortive treatments attenuate symptoms arise from acute migraine attacks whereas preventative medications specifically aim at reducing attack severity and frequency. Although several prophylactic medications have been developed for migraine patients, © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. no consensus has been reached with respect to their relative efficacy, safety and tolerability [7]. Furthermore, some medications appear to provide inadequate relief since they are not effective to all migraine patients [8]. As a result, some meta-analysis has been designed to compare the relative efficacy between different medications and some conclusions have been obtained in the current literature. For instance, patients treated by sodium valproate were associated with a lower risk of headache compared to the control group [9]. Furthermore, triptans and non-triptans appear to provide patients with different levels of relief [10]. Nevertheless, the current literature does not contain adequate studies that are able to identify the most preferable prophylactic medication for migraine patients and there is an increasing demand for discriminating the availa (...truncated)


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Aijie He, Dehua Song, Lei Zhang, Chen Li. Unveiling the relative efficacy, safety and tolerability of prophylactic medications for migraine: pairwise and network-meta analysis, The Journal of Headache and Pain, 2017, pp. 26, Volume 18, Issue 1, DOI: 10.1186/s10194-017-0720-7