Effectiveness and acceptability of oral migraine preventives: A prospective, observational study.

OBJECTIVE: To explore the adherence, effectiveness, safety, tolerability, and acceptability of frequently used oral migraine preventive drugs in a real-world setting. BACKGROUND: Oral migraine preventives are previously mainly explored in randomized controlled trials, whereas real-world data on treatment outcomes remain limited. METHODS: MigriNor was a prospective observational cohort study conducted from May 2021 to June 2024 at St. Olav's University Hospital, Trondheim, Norway. The study included participants with migraine who started oral preventive treatment, including candesartan, amitriptyline, metoprolol, or topiramate. Migraine diagnosis, according to the ICHD-3, was verified by a neurologist at inclusion. Participants recorded daily entries in an electronic headache diary during a 4-week baseline period before beginning treatment, followed by a 12-week follow-up period with telephone consultations every 4 weeks. If a change of preventive drug was necessary, participants were allowed to re-enter the study using the same baseline period. Change from baseline in moderate-to-severe headache days was the primary effectiveness endpoint. Drug acceptability outcomes were collected at 12 weeks or at the time of discontinuation. RESULTS: A total of 254 participants were included, 51.2% of them had chronic migraine and 48.8% had episodic migraine. Of all participants, 6.7% had previous treatment failure of at least three preventive drugs and 18.1% had baseline medication overuse. Candesartan and amitriptyline demonstrated similar reductions in moderate-severe headache days from baseline to weeks 9 to 12 (-2.4 days, 95% confidence interval: [-3.0 to -1.9], p < 0.001 for candesartan, and -2.4 days, 95% confidence interval: [-3.1 to -1.6], p < 0.001 for amitriptyline). The study was unable to detect a significant reduction of moderate-severe headache days from baseline to weeks 9 to 12 for metoprolol and topiramate, but both demonstrated effectiveness for several secondary outcomes. High proportions of participants (22.3% to 46.8%, depending on the drug used) discontinued preventive treatment before 12 weeks. Candesartan had the lowest mean number of adverse drug reactions (1.3), the lowest proportion of participants experiencing at least one adverse drug reaction (77.1%), and high acceptability. Topiramate had the highest mean number of adverse drug reactions (4.2), a large proportion of participants experiencing at least one adverse drug reaction (95.7%), and low acceptability. CONCLUSION: Because this was an observational study characterized by imbalanced group sizes and absence of randomization, the comparability across drugs was limited. Candesartan and amitriptyline both significantly reduced the number of moderate-severe headache days with candesartan having fewer adverse events and higher acceptability. A significant reduction in moderate-severe headache days was not detected for topiramate and metoprolol, but both demonstrated effectiveness for several other measured outcomes. Topiramate had severe acceptability issues, whereas metoprolol had intermediate acceptability.