A systematic review by the American Academy of Neurology and American Headache Society in Neurology (August 2026) covered 217 randomised trials of preventive drugs in adults, to June 2024, and graded confidence using a modified GRADE approach. It informs a companion guideline.
For episodic migraine, high-confidence evidence supported galcanezumab and erenumab; moderate confidence supported atogepant, eptinezumab, fremanezumab, propranolol, topiramate and valproate. Amitriptyline, flunarizine, metoprolol, bisoprolol, levetiracetam, fluoxetine, nifedipine, pizotifen and telmisartan had low-confidence evidence of possible benefit. For chronic migraine, high confidence supported fremanezumab, galcanezumab and onabotulinumtoxinA; moderate confidence supported atogepant, eptinezumab, erenumab, topiramate and valproate.
Head-to-head evidence was sparse and low confidence, so the review cannot rank drugs against each other. Several widely used agents — amitriptyline and flunarizine in particular — rest on weaker trial evidence than their place in practice suggests.
In India, cost dominates: CGRP-targeted drugs remain out of reach for most patients, so the moderate-confidence oral options are where most prevention will start.
- Offer prevention to patients with frequent or disabling migraine; several drugs have moderate or high-confidence evidence
- Start with propranolol or topiramate where cost matters; both had moderate-confidence evidence
- Avoid valproate and topiramate in women who may become pregnant
- Consider CGRP monoclonal antibodies or onabotulinumtoxinA for chronic migraine where affordable
- Recognise that amitriptyline and flunarizine rest on low-confidence evidence
Why it matters
It exposes how thin the trial evidence is for some of the most prescribed preventives, including amitriptyline and flunarizine.
Don't overread it
Few trials compared active drugs, so the review does not show one preventive is better than another.
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