Use of Beta-Blocker Ophthalmic Solution for the Treatment of Migraine

         In the annals of migraine, one of the most fascinating stories is how, in 1966, a physician named Robert Rabkin observed that the drug propranolol could prevent migraine. Dr. Rabkin was actually conducting a study using a beta-blocker (propranolol) to treat heart pain (angina) and fortuitously observed that one of his research subjects had a remarkable reduction in the frequency of his migraine attacks. A decade later, Drs. Seymour Diamond and John Graham presented their experience treating 86 migraine patients with daily propranolol to the Food and Drug Administration (FDA), and demonstrated that propranolol was indeed efficacious and safe for migraine prophylactic therapy. Subsequently, propranolol became the first FDA-approved medication for the prevention of migraine.

As one of many beta blockers used commonly to prevent migraine, propranolol currently, is probably the most widely prescribed medication in the world for prevention of migraine. Beta blockers are used to treat multiple diseases including high blood pressure, heart pain, and irregularities of the heart as well as conditions such as anxiety and certain types of tremors. Beta blockers have been so successful that they are considered one of the most important medical discoveries of the 20thcentury.

In 1978, a second beta blocker, timolol, also received FDA approval as the first topical beta blocker for the treatment of glaucoma. Although clinical trials demonstrated a very strong benefit from using timolol as a migraine preventive, neither it nor propranolol have demonstrated efficacy as an acute treatment for migraine. However, these previous studies have focused on oral preparations of these drugs and the drug was not absorbed quickly enough to be effective as an acute treatment. Interestingly, since the 1980s, there have been rare case reports of patients with glaucoma being treated with timolol eye drops who experienced migraine relief.

Considering the history of these beta blockers, two ophthalmologists—John Hagen and Carl Migliazzo—recently made a startling observation. During a game of golf, these ophthalmologists had an “eureka” moment while discussing possible treatment options for Dr. Hagen’s daughters who experience migraine. They observed that some of their patients treated for glaucoma with timolol eye drops reported that if the timolol eye drops were instilled during a migraine, the headache would be rapidly terminated.

Following their discussion on the use of beta blocker eye drops for the treatment of acute migraine, Drs. Hagen and Migliazzo reported on a series of seven patients who had successfully treated acute attacks of migraine with timolol eye drops, which was published in The Journal of the Missouri State Medical Association in 2014. The seven patients in these case reports were all female, ages 38 to 76, who presented with migraine syndromes, with and without aura. Five of the seven patients reported complete pain relief, with one patient reporting complete pain relief within 10 minutes of treatment. The two remaining patients reported pain relief of 8 and 9.5 on a 1 to 10 scale, with 10 representing complete relief. These patients were all instructed to use 1 or 2 drops of their beta blocker eye drops as early as possible during their acute migraine attacks. Patients were advised to blink several times to encourage the eye drop to pass into the lacrimal drainage duct. Interestingly, one patient used timolol drops sublingually and reported receiving pain relief. The dye drops were generally well-tolerated with only one reported side effect of shortness of breath which only occurred if eye drops were used in both eyes. Drs. Hagen and Migliazzo stress all patients underwent a complete medical history and ophthalmic examination prior to the initiation of topical beta blockers. Patients were advised to read the package insert and inform their primary care physicians of their acute use of beta blocker eye drops.

Since the publication of these reports, Drs. Hagen and Migliazzo have received multiple messages and phone calls from fellow physicians who have reported success with patients using beta blocker eye drops for migraine relief. Although these represent only a few case reports, they provide additional evidence of the use of topical beta blockers in acute migraine, and the treatment appears to be well-tolerated. The physicians are hopeful to see the development of well-controlled studies to validate the efficacy of beta blocker eye drops for acute migraine relief.