Propranolol and amitriptyline in prophylaxis of migraine. Pharmacokinetic and therapeutic effects
D. K. Ziegler, A. Hurwitz, S. Preskorn, R. Hassanein and J. Seim
Department of Neurology, University of Kansas Medical Center, Kansas City, 66160-7314.
OBJECTIVES--To determine if the effectiveness of propranolol hydrochloride
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 other
medication. DESIGN--Three-month modules of treatment with each drug and
placebo in a randomized crossover design. Headache scores from daily
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--Thirty
consecutive patients with a history of frequent migraine. MAIN OUTCOME
MEASUREMENTS--From headache scores, patients were classified as either
propranolol responders, amitriptyline responders, or nonspecific
responders. Clinical variables as predictors of response to medications
were studied, as were effects on frequency, duration, and/or severity of
headache. RESULTS AND CONCLUSIONS--No significant correlations were found
between changes in headache score and blood level of drug or change in any
of the physiologic measurements. Amitriptyline significantly reduced the
severity, frequency, and duration of headache attacks; propranolol reduced
the severity of attacks only. Amitriptyline response was correlated with
female gender and baseline headaches of shortest duration and of highest
frequency. Propranolol response was associated with attacks of greatest
duration at baseline and with low pulse rise with exercise at baseline.
Nonspecific response was associated with male gender and most frequent
headaches by history.
