Recalling My Role in Propranolol Research in Migraine Preventive Therapy
Seymour Diamond, MD Chicago, IL
As my headache practice grew during the 1970s, I was always keen on identifying new options for migraine prevention. An article on the use of the beta blocker, propranolol, in angina pectoris, was published by Rabkin and his colleagues in 1966, and incidentally reported on a patient who had managed to control his migraine attacks while being treated with propranolol. In 1972, in the journal, Neurology, Weber and Reinmuth expanded our knowledge of the topic by describing their work using propranolol for a group of migraine patients. These articles piqued my curiosity and by 1973, I had begun prescribing propranolol for some of my patients, although the drug had not been approved by the Food and Drug Administration( FDA) for migraine prevention.
In my clinical practice, patients treated with propranolol were reporting significant decreases in the frequency and duration of their migraine attacks. Subsequently, I contacted Ayerst Laboratories, the manufacturers of propranolol, and suggested that they undertake clinical studies on propranolol use in migraine, in order to obtain approval by the FDA for that indication. Rudy Widemark, MD, was the physician supervising research at Ayerst, and he visited my office and agreed to initiate these studies. Through our collaboration, Dr. Widemark and I became friends. Later, when Rudy joined the staff at the FDA, he invited me to serve as a headache consultant.
With my colleague, Jose L. Medina, MD, I published the results of a study involving 83 patients who used either propranolol or placebo for migraine prevention. Sixty-two patients completed the study. The article was published in the March, 1976, issue of the journal, Headache. Later that year, I traveled to Bethesda, MD, at the invitation of the FDA to appear before a panel of noted neurologists from across the US. At that meeting, I discussed the results of my study as well as that of John Graham, MD, of Faulkner Hospital, Boston.
Despite the small number of patients involved in the two studies, the indication for propranolol use in migraine prevention was approved. However, the panel limited the indication to non-classical migraine( migraine without aura). At first, I wanted to argue the point because there were few patients in the 1976 study who were diagnosed with classical migraine( migraine with aura). Subsequently, I considered my argument carefully because at that time, there was little consensus in the medical community that both types of migraine acted similarly. Also, I did not want to stall the approval process for propranolol.
During the next decade, we continued to study the long-term use of propranolol as well as a long-acting form of the drug to ensure patient compliance with a once-daily dose. Propranolol is probably the most widely used drug in migraine prevention. In the accompanying article by the group at the Headache Care Center, the suggested novel approach to acute migraine therapy with a beta blocker ophthalmic solution may provide significant help to migraine patients. And it can easily trace its roots back to an incidental finding in 1966. HW
Suggested reading Diamond S, Medina JL. Double blind study of propranolol for migraine prophylaxis. Headache 1976; 16:24-27.
Diamond S, Solomon GD, Freitag FG, Mehta ND. Long-acting propranolol in the prophylaxis of migraine. Headache 1987; 27:70-72.
Rabkin R, Stables DP, Levin NW, et al. The prophylactic value of propranolol in angina pectoris. Am J Cardiol 1966; 18:370-380.
Weber RB, Reinmuth OM. The treatment of migraine with propranolol. Neurology 1972; 366-369.
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