title: Unveiling the relative efficacy, safety and tolerability of prophylactic medications for migraine: pairwise and network-meta analysis.
abstract: 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.
authors.affiliation: Department of Neurosurgery, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, 264000, Yantai, Shandong, China.
authors.forename: Aijie
authors.initials: A
authors.lastname: He
authors.affiliation: Department of Radiotherapy, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, 264000, Yantai, Shandong, China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Pharmacy, Yantai Hospital of Traditional Chinese Medicine, 264000, Yantai, Shandong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, Yantai Hospital of Traditional Chinese Medicine, No. 39 Xingfu Road, Zhifu Disctrict, 264000, Yantai, Shandong, China. dqchangzhigang@126.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
mesh_terms: D000328:Adult; D000588:Amines / Q000009:adverse effects / Q000627:therapeutic use; D000639:Amitriptyline / Q000009:adverse effects / Q000627:therapeutic use; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D003509:Cyclohexanecarboxylic Acids / Q000009:adverse effects / Q000627:therapeutic use; D004244:Dizziness / Q000139:chemically induced / Q000175:diagnosis; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000175:diagnosis* / Q000188:drug therapy*; D009325:Nausea / Q000139:chemically induced / Q000175:diagnosis; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D011433:Propranolol / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D000077236:Topiramate; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D000077236:Topiramate; D000639:Amitriptyline; D005632:Fructose; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D000077206:Gabapentin; D011433:Propranolol
keywords: Efficacy; Migraine; Network meta-analysis; Safety; Tolerability