Timolol Eyedrops Ease Migraine Pain
JAMA Ophthalmology, November 2020
Migraine is a debilitating condition and a leading cause of disability worldwide. Oral timolol maleate, a beta-blocker, is an FDA-approved drug for migraine prophylaxis. Although oral beta-blockers cannot ease migraine pain, topical preparations of these drugs have reduced pain in case reports and a small series of patients, warranting larger studies. In a double-masked randomized trial, Kurian et al. evaluated the short-term efficacy and safety of timolol maleate ophthalmic solution in the treatment of acute migraine pain. They found that these eyedrops were superior to placebo in lowering pain scores. No adverse events were noted.
For this single-center study, 50 patients with migraine were assigned randomly to receive either timolol eyedrops (0.5%) or placebo eyedrops. The participants were instructed to instill one drop of solution in each eye as soon as a migraine began. After three months on the initial regimen, there was a washout period of one month, followed by three months of the opposite regimen. Patients graded the pain of each migraine on a scale of 0-10, both before and after use of the eyedrops. The main outcome measure was reduction in pain score by four points (or to zero) 20 minutes after applying the drops.
During the study, there were 619 episodes of migraine. Of these, 284 (46%) were treated with timolol, 271 (44%) received placebo, and 64 (10%) occurred during the washout period. Seven patients withdrew after randomization. Of the timolol-treated migraines, 233 (82%) met the primary end point, compared with 38 (14%) of migraines that received placebo drops. A generalized estimating equation analysis showed that the mean reduction in pain score at 20 minutes was 4.63 points greater in the timolol group (p < .001). No adverse reactions or systemic adverse effects occurred during the study.
These findings indicate that topically applied beta-blockers can quickly alleviate migraine pain in many patients. The drops can, at least theoretically, abolish confounding factors such as high first-pass metabolism, said the authors. Thus, the drugs hold promise as a “welcome addition to existing medications for abortive pharmacotherapy of acute migraine.”
The authors recommend multicenter studies that involve assessments at later time points, including two and four hours after dosing. (Also see related commentary by Bradley J. Katz, MD, PhD, in the same issue.)
The original article can be found here.