In the randomized, masked placebo-controlled crossover trial involving 50 patients, pain levels were reduced at 20 minutes by four points, or to zero, in 233 migraines (82%) treated with the eye drops compared with 38 (14%) of the placebo-treated attacks, researchers report in JAMA Ophthalmology.
"The factor precluding the use of oral beta-blockers in acute migraine attacks is proposed to be its high first-pass metabolism and time taken to achieve peak plasma levels," the researchers, led by Dr. Abraham Kurian of the Chaithanya Eye Hospital and Research Institute, write. "Unlike oral administration, ophthalmically administered beta-blockers bypass first-pass metabolism by the liver. Because the pharmacokinetics of nasopharyngeal absorption may be similar to those of an intravenous bolus, plasma levels are achieved very quickly with topical administration."
Used daily, oral beta-blockers have been shown to successfully prevent migraine attacks.
To explore the possibility that timolol might alleviate migraine pain, Dr. Kurian and his colleagues recruited 50 patients, including 42 who were female. The patients' average age was 27.3 years. The plan was to randomize the 50 to get either timolol, 0.5%, or placebo over a three-month treatment period, and then, after a one-month washout period, have the patients cross-over to the opposite group.
After the randomization visit, seven patients dropped out of the study. Of the remaining 43 patients, 38 completed the seven-month follow-up.
The patients were instructed to use one drop of their assigned medication in each eye at the earliest onset of migraine aura or headache and to use another drop at 10 minutes if there was no pain relief with the first drops. If after 20 minutes the patients had no pain relief, they were free to use any other oral medication to treat their migraine. Prophylactic anti-migraine medications were not allowed.
For each migraine attack, patients were asked to record the details in a diary that was collected at each visit. Patients were asked about adherence to treatment and to report any serious medical event or adverse event during the intervening period.
During the course of the study, the patients experienced a total of 619 migraine attacks, 284 (46%) of which were treated with timolol, 271 (44%) were treated with placebo and 64 (10%) occurred during the washout period and were untreated. The average pain score at the onset of migraine attacks was 6.01 for the 284 treated with timolol and 5.93 for the 271 treated with placebo.
The average reduction in pain scores in the timolol treated migraines was 5.98. The average reduction in the placebo treated attacks was 0.93.
The new study is "very interesting," said Dr. Robert Kanieki, an associate professor of neurology at the University of Pittsburgh School of Medicine and director of the UPMC Headache Center. "As headache specialists we are always looking for tools," Dr. Kanieki added. "This is more than preliminary, but still far short of being confirmatory."
For a timolol eye drop study to be confirmatory, there would need to be pain data at two hours and 24 hours after treatment was taken, Dr. Kanieki said. That's the only way to know whether the migraines returned, he explained.
Most likely the eye drops are working through the serotonin circuits, Dr. Kanieki said. That is the circuitry impacted by drugs approved to acutely treat migraine attacks, he added.
The good news is that timolol eye drops are widely available as they are used to treat glaucoma, Dr. Kanieki said.
By Linda Carroll
SOURCE: https://bit.ly/2GgYmJz and https://bit.ly/3jyjqJK JAMA Ophthalmology, online October 1, 2020.
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