PROPRANOLOL FOR MIGRAINE PROPHYLAXIS Bengt Forssman, M.D. K-G Henriksson, M.D. Valur Johannsson, M.D. Lars Lindvall, B.A. Hakan Lundin, M.D. From University Hospital, Linköping, Sweden. Accepted for publication: 8/6/76 SYNOPSIS The preventive effect of propranolol on migraine attacks was compared to placebo in a double-blind cross-over trial. Thirty-two patients with serious and prolonged migraine participated in the 12-week study. The effect of propranolol was significantly better than that of placebo. The number of migraine attacks during the propranolol period was reduced in 22 patients (69%), and in 11 of these (34%) a reduction of more than 50% was seen. The intensity of headache was significantly reduced during the propranolol period. The intake of analgesics and preparations containing ergotamine was significantly reduced during the propranolol period also. No serious side effects were noted. (Headache 16:238-245) NO UNIVERSALLY effective prophylactic therapy is available for migraine; nor is preventive medication indicated in all migraineurs. The choice of drugs for prophylaxis is a question of trial and error. Serotonin antagonists (methysergide, pizotifen, cyproheptadine) and progestagens (flumedroxone) have been used for a number of years.1,2,3 Recently, clonidine has also been tried as a migraine prophylactic.4,5 In 1966, Rabkin et al.6 published a report on a patient who was relieved of his attacks of migraine when treated with propranolol for angina pectoris. Since then the effect of propranolol in migraine has been described by investigators in different parts of the world, but only a small number of double-blind studies on the prevention of migraine with propranolol have been published (Table 1). All but one7 of these investigations were performed on adults. Our own investigation is a double-blind study in which we have compared the results of placebo and propranolol therapy using a cross-over technique. METHODS Initially, the study included 40 patients. In addition to a diagnosis of migraine, the following criteria were established for participation in the investigation: 1) Age between 16 and 55 years; 2) At least three attacks per month; 3) No pregnancy or suspicion of pregnancy; 4) No indication of renal or heart disease, hypertension, diabetes or asthma; 5) No history of earlier treatment of migraine with propranolol. Four patients dropped out because of side-effects (two patients during the course of propranolol therapy, one during placebo therapy and one during placebo therapy with side-effects which were the same during both propranolol and placebo periods). Four patients were excluded from the final assessment because of incomplete records. Of the 32 patients who completed the trial, 28 were females and 4 males. The ages ranged between 17 and 51 years (mean: 37.4 years). Five patients had "classic" migraine (migraine with neurologic symptoms during the aura) and 27 had "common" migraine (attacks without aura).8 The duration of migraine in those completing the trial ranged between 2 and 40 years (mean: 18.9 years). Thirty-nine patients had family histories of migraine. All but one had nausea and vomiting with the attacks. The headaches were hemilateral in all patients.
INVESTIGATORS Weber, Reinmuth (1972)18 Malvea, Gwon, Graham (1973)19
Børgesen, Lanng, Nielsen, Mailer (1974)20
TABLE I DOUBLE-BLIND CROSS-OVER TRIALS (PLACEBO/PROPRANOLOL) NO OF PERIOD PERIOD PERIOD PATIENTS 1 2 3 DOSE/DAY RESULTS 19 missing 12 wks. 12 wks. 80 mg 15 patients better on propranolol than placebo 12 patients with reduction of attacks by >50%. 29 30 days 6 wks. 6 wks. ? Number of "headache units"/day during observation period: 25.4; during placebo period: 23.3; during propranolol period: 18.6. In patients with a preference for propranolol (16) the "headache unit"/day figure was 0.68 during the observation and placebo periods and 0.25 during the propranolol period. Headache units: 1 unit: slight headache; 2 units: moderate headache; 3 units: severe headache. 30 4 wks. 8 wks.* 8 wks.* 120 mg Attack frequency: Compared with placebo, 9 patients showed a reduction by 50% or more, 9 patients a reduction by less than 50%. Attack frequency unchanged or increased in 12 patients. 28 missing 13 wks. 13 wks. Weight Study on children (7-16 35kg years). 20 patients free 60mg from attacks on Weight propranolol, reduction of >35kg 120mg attacks by at least 2/3 in 3 patients, reduction of attacks by