PROPRANOLOL AND AMITRIPTYLINE IN PROPHYLAXIS OF MIGRAINE - PHARMACOKINETIC AND THERAPEUTIC EFFECTS

objectives.-To determine if the effectiveness of propranolol hydrochlo ride and amitriptyline hydrochloride are correlated with blood levels and/or with standardized test of pharmacologic effect and to determine which clinical variables are predictors of response to one or the oth er medication. Design.-Three-month modules of treatment with each drug and placebo in a randomized crossover design. Headache scores from da ily diaries were calculated at monthly intervals, as were simultaneous blood levels of drug, supine and standing blood pressure, pulse rise with exercise, and salivary flow. Setting.-Outpatient headache clinic at the University of Kansas Medical Center, Kansas City. Patients.-Thi rty consecutive patients with a history of frequent migraine. Main Out come Measurements.-From headache scores, patients were classified as e ither propranolol responders, amitriptyline responders, or nonspecific responders. Clinical variables as predictors of response to medicatio ns were studied, as were effects on frequency, duration, and/or severi ty of headache. Results and Conclusions.-No significant correlations w ere found between changes in headache score and blood level of drug or change in any of the physiologic measurements. Amitriptyline signific antly reduced the severity, frequency, and duration of headache attack s; propranolol reduced the severity of attacks only. Amitriptyline res ponse was correlated with female gender and baseline headaches of shor test duration and of highest frequency. Propranolol response was assoc iated with attacks of greatest duration at baseline and with low pulse rise with exercise at baseline. Nonspecific response was associated w ith male gender and most frequent headaches by history.