Timolol Eyedrops Evaluated for Acute Migraine Treatment

During the study, 50 migraine patients randomly received either topically applied timolol maleate ophthalmic solution, 0.5%, or placebo eyedrops.

Timolol maleate ophthalmic solution was found to be effective in managing acute migraine pain suggesting that topically applied β-blockers may be a promising therapeutic option for the management of acute migraine attacks, according to a recently published randomized crossover trial.

To investigate the safety and short-term efficacy of topically applied β-blockers for the treatment of acute migraine pain, the study authors conducted a masked, placebo-controlled study between May 27, 2015 and August 28, 2017 at the Chaithanya Eye Hospital and Research Institute in Trivandrum, India.

During the study, 50 migraine patients randomly received either timolol maleate ophthalmic solution, 0.5%, or placebo eyedrops (carboxymethyl cellulose, 0.5%) and were instructed to use 1 drop of the medication in each eye at the onset of their migraine. The primary outcome of the study was pain score reduction by 4 points, or to zero, 20 minutes following the instillation of the eyedrop.

The average (SD) age of the patients included in the study was reported to be 27.3 (11.3) years and 84% (n=42) were female. Of the total 619 migraine attacks reported to have occurred during the study, 46% (n=284) were treated with timolol, 44% (n=271) were treated with placebo, and 10% (n=64) were not treated by a study medication since they occurred during the washout period; 14% (n=7) of patients withdrew from the study following randomization.

The study authors reported that at 20 minutes after the instillation of the eyedrops, 82% (n=233) of timolol-treated migraine attacks were associated with a pain score reduction of 4 points, or to zero, compared with 14% (n=38) of placebo-treated attacks, which correlated to a difference of 68 percentage points (95% CI, 62-74).  It was noted that timolol eyedrops were administered again 10 minutes after the first administration in 42% (n=120) of the attacks.

Additionally, an analysis using generalized estimating equations revealed a greater reduction in the pain score at 20 minutes for patients who received timolol compared to those who received placebo by a mean (SE) of 4.63 (0.34) points (P <.001).

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“The study supports consideration of timolol eyedrops in aborting acute migraine attacks compared with placebo eyedrops,” the study authors concluded. “Use of topical β-blockers can at least theoretically abolish confounding factors such as high first-pass metabolism and holds the promise to be a welcome addition to existing medications for abortive pharmacotherapy of acute migraine.”


  1. Kurian A, Reghunadhan I, Thilak P, Soman I, Nair U. Short-term efficacy and safety of topical β-Blockers (timolol maleate ophthalmic solution, 0.5%) in acute migraine [published online October 1, 2020]. JAMA Ophthalmol. 2020. doi: 10.1001/jamaophthalmol.2020.3676.