Responders and Non-Responders to Metoprolol, Propranolol and Nifedipine Treatment in Migraine Prophylaxis: A Dose-Range Study Based on Time-Series Analysis

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Abstract
The aim of the present study was to ascertain, on the basis of single case statistics and time-series analysis, responder and non-responder rates for metoprolol, propranolol and nifedipine in migraine prophylaxis. In addition, an attempt was made to identify the dose relationship for the various drugs on headache parameters. In a double-blind dose-finding study, 58 patients were treated in five consecutive dosage steps each lasting 1-3 months. All patients kept a headache diary before, during and after treatment. Serum drug levels were also determined. The data were assessed by time-series analysis, as well as by multiple regression and analysis of variance. A significant improvement was noted in 54.4% of patients with migraine during treatment with metoprolol. The study did not confirm the high success rates in migraine prophylaxis of nifedipine and propranolol quoted in the literature. Administration of nifedipine led to an increase in migraine attacks in 71% of the patients. Nifedipine was of no value in the prophylaxis of migraine. Only 32% of patients showed a reduction in frequency of migraine attacks during administration of propranolol. The analysis of variance failed to show any significant difference between the responder rates for metoprolol and propranolol. Higher doses of propranolol and metoprolol were more effective. Multiple regression analysis explained a considerable part of variance for propranolol (but not for metoprolol) as a result of reduced intake of ergotamine preparations and analgesics. It can therefore be concluded that part of the prophylactic effect of propranolol is attributable to a reduction in the use of migraine medication.

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