Clonidine in Migraine Prophylaxis T. Kallanranta, H. Hakkarainen, E. Hokkanen, T. Tuovinen Department of Neurology, University Central Hospital, Oulu and Department of Neurology, University Central Hospital, Tampere, Finland (Drs. Kallanranta, Hakkarainen, Hokkanen, Tuovinen). Reprint requests to: Dr. Tapani Kallanranta, Department of Neurology, University of Central Hospital of Oulu, 90220 Oulu 22, Finland. Accepted for Publication: 6/21/77 SYNOPSIS Clonidine chloride, 25 ug three times per day, decreased the mean number of headache attacks per month to 2.26 compared to 3.94 before treatment and 2.98 during placebo use in 50 migraineurs. Fifty ug clonidine t.i.d. decreased mean number of attacks from 4 before treatment to 1.88 during treatment and 2.49 during placebo. Frequency of attacks decreased in 44% of patients, were unchanged in 46% of patients and increased in 10% of patients on 25 ug t.i.d., and 50 ug clonidine t.i.d. decreased attacks in 58% of patients, frequency was unchanged in 40% of patients and increased in 1%. Practolol, a beta adrenergic blocker, decreased frequency of attacks in 41% of patients, attack frequency was unchanged in 42% of patients, and increased frequency in 16% of patients receiving it 50 mg t.i.d. Mean duration of attacks decreased from 3.86 hours before treatment to 2.16 hours after clonidine in the 25 ug t.i.d. dosage and to 1.86 after clondine in the 50 ug t.i.d. dose. Attack duration was 2.37 hours after practolol therapy and 3.36 hours after placebo. The duration of attacks were decreased in 38% of patients receiving 25 ug of clonidine t.i.d., were unchanged in 60% and increased in 2%. In those patients receiving 50 ug clonidine t.i.d. duration of attacks were decreased in 52%, unchanged in 46% and increased in 2%. With practolol 50 mg t.i.d. duration of attacks were decreased in 41%, unchanged in 43% and increased in 16% of patients. Prodromal symptoms were not reduced by clonidine in the 25 or 50 ug t.i.d. dose nor with practolol. Medication was not clearly effective in improving general well-being or ability to work of patients receiving clonidine in either dose nor practolol. Practolol was associated with sedation in 21% of patients. Increased clonidine dose was associated with sedation in 21% of patients. Increased clonidine dose was associated with increased nausea and sedation. It was concluded that practolol has insufficient anti-migraine effect to justify its use as a routine prophylactic agent. Clonidine is useful in the prophylactic treatment of migraine. (Headache 17:169-172, 1977) CLONIDINE, an imidazolene derivative, is widely used as an antihypertensive drug. Several investigators have reported favorable results with its use in the prophylaxis of migraine in doses ranging from 50 to 150 ug/day.1-4 Reduced frequency and severity of attacks, especially in so-called tyramine-sensitive subjects5 were observed in 25% to 65% of patients depending upon methods and length of follow-up. The purpose of our study was to determine the effect of clonidine compared with placebo in the prophylaxis of migraine, to evaluate the effect of increasing the daily dose from 50 ug to 150 ug/day, and to answer the questions, does extension of treatment from one to two months affect the results?, does the beta-blocker practolol, have anti-migraine activity? PATIENTS AND METHODS The study consisted of two parts, which were separated by one and one-half years. Patients were fifty migraineurs who were seen in the Neurology Polyclinics of Oulu University Central Hospital and Tampere Central Hospital and who had at least one attack of migraine during the month preceding the study. There were 36 women and 14 men, 20 to 49 years of age, mean age 31.6 years, 24 with classic migraine and 26 with common migraine in the first study. Six of this group had dietary migraine. Mean frequency of attacks in the month preceding the study was 3.94 (sd 2.19 pl 10). Thirty-two women and 18 men, 22 to 55 years of age, mean age 36.3 years, were in the second study. Fourteen patients had classic migraine and 36 common migraine. Three patients had dietary migraine. Frequency of attacks in the month preceding the study was 4 (sd 2.20 pl 11). The patients kept a record of time and duration of each attack, associated symptoms, and possible side effects of the drug. They were allowed to use their usual analgesic treatment for headache attacks. In the first part of the study every patient used clonidine chloride 25 ug three times per day for one month and an identical placebo tablet also 3 times per day for one month. There was a one week cross-over period. Every other patient received first clonidine and then placebo and every other patient received the drugs in reversed order.

In the second part of the study the clonidine dose was 50 ug three times per day for two months and an identical tablet, practolol was used, 50 mg three times per day. The cross-over period and administration of the drug were the same as in the first part of the study. Table 1 indicates the frequency of migraine attacks per month. A statistically significant therapeutic effect of clonidine vs placebo (p