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 eye 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 case reports, Drs. Hagen and Migliazzo have received multiple messages and phone calls from fellow physicians who have reported success with patients using beta blocker eyes 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 wellcontrolled studies to validate the efficacy of beta blocker eye drops for acute migraine relief.
How Would Beta Blockers Work in Acute Treatment of Migraine? The exact mechanism of beta blockers in the treatment or prevention of migraine is unknown. Beta blockers work primarily by blocking the stimulating or activating effects of adrenalin. Considering that individuals with migraine have inherited a nervous system that is more excitable than those without migraine, it is easy to assume that beta blockers may in some way reduce this inherent excitability. In other words, the beta blockers may make the nervous system less vulnerable to migraine. While this likely explains the migraine prevention benefits, it also may provide a rationale for their use in the acute treatment of migraine headaches.
One can imagine that during a migraine, the threshold for nervous system activation has already been surpassed and hence the process of migraine occurs. Beta blocker eye drops enter the nasal cavity through the lacrimal duct( a small passageway from the eye to the nose that drains tears from the eye) very quickly. Once in the nose, the eye drops are rapidly absorbed into the blood. Conceivably, they could block the activating effects of adrenaline and allow the nervous system to reverse migraine. Beyond the speed of entry into the blood, another major advantage of nasal absorption is that medications do not have to pass through the liver before entering the systemic circulation, thus avoiding their metabolism by the liver and allowing a much smaller dose of medication to be effective. Beta blockers have also been found to reduce the electrical excitability of nerve cells, and this too may be part of their potential mechanism.
When oral preparations of beta blockers are used to prevent migraine, levels build up slowly in the blood. This action works well for prevention but during migraine, these levels would increase too slowly to be effective. Using an eye drop with rapid absorption through the nose circumvents that problem. Also, nerves in the nasal cavity may become activated and potentially, beta blockers could act directly on these nerves. Finally, it is possible that some of the beta blocker eye drop could be absorbed into the brain and exert their beneficial effect in that manner.
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