ORAL migraine preventives reduced headache burden in real world care, but tolerability varied sharply across commonly used drugs.
Oral Migraine Preventives Compared in Practice
A prospective observational study has shown that oral migraine preventives can deliver meaningful benefits in clinical practice, although effectiveness and acceptability differed across commonly used therapies.
The MigriNor study followed 254 participants with migraine who began oral preventive treatment with candesartan, amitriptyline, metoprolol, or topiramate at St. Olav’s University Hospital in Trondheim, Norway. Migraine diagnosis was verified by a neurologist according to ICHD-3 criteria. Participants completed daily entries in an electronic headache diary during a 4-week baseline period before starting treatment, followed by 12 weeks of follow-up with telephone consultations every 4 weeks.
Just over half of the cohort had chronic migraine, while 48.8% had episodic migraine. Medication overuse was present at baseline in 18.1% of participants, and 6.7% had previously failed at least three preventive drugs.
Candesartan and Amitriptyline Show Similar Benefit
Candesartan and amitriptyline produced comparable reductions in moderate-to-severe headache days from baseline to weeks 9 to 12. Both were associated with a mean reduction of 2.4 days, with statistically significant improvement reported for each drug.
The study did not detect a significant reduction in moderate-to-severe headache days for metoprolol or topiramate over the same period. However, both drugs showed effectiveness across several secondary outcomes, suggesting that treatment benefit may not be fully captured by the primary endpoint alone.
Acceptability Remains a Key Migraine Treatment Barrier
Discontinuation before 12 weeks was common, ranging from 22.3% to 46.8% depending on the drug used. This finding reinforces tolerability as a central issue in migraine prevention, particularly when oral migraine preventives are used in real world settings rather than tightly controlled trials.
Candesartan had the lowest mean number of adverse drug reactions, at 1.3, and the lowest proportion of participants reporting at least one adverse drug reaction, at 77.1%. It also showed high acceptability. Topiramate had the highest mean number of adverse drug reactions, at 4.2, with 95.7% of participants reporting at least one adverse drug reaction, alongside low acceptability.
Because the study was observational, lacked randomization, and included imbalanced group sizes, direct comparison between drugs remains limited. Still, the findings suggest that candesartan and amitriptyline may offer meaningful reductions in headache burden, while tolerability and patient acceptability should remain central to migraine prevention decisions.
Reference
Riise HS et al. Effectiveness and acceptability of oral migraine preventives: A prospective, observational study. Headache. 2026;10.1111/head.70061.
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