Dextroamphetamine Pilot Crossover Trials and n of 1 Trials in Patients With Chronic Tension-Type and Migraine Headache


  • David C. Haas MD,

  • Paul R. Sheehe ScD

  • From the Department of Neurology (Dr. Haas) and the Department of Neuroscience and Physiology (Dr. Sheehe), State University of New York Upstate Medical University, Syracuse, NY.

Address all correspondence to Dr. David Haas, Department of Neurology, University Health Care Center, 90 Presidential Plaza, Syracuse, NY 13202.


Objective.—To examine the preventive effects of dextroamphetamine in select small groups of patients with chronic tension-type and migraine headache.

Background.—Neither amphetamine nor methylphenidate is used as a headache preventive. This study was undertaken after a chance observation led one of us to prescribe dextroamphetamine with apparent successes in specific patients with chronic tension-type or migraine headaches.

Methods.—Two pilot trials were done. Trial 1 tested patients who were taking dextroamphetamine, while Trial 2 tested patients who had never taken this drug. Each trial obtained full data on eight subjects with chronic tension-type headache and eight subjects with migraine headache. A randomized, double-blinded, controlled, multiple-crossover design was used. Subjects took capsules containing dextroamphetamine or equi-stimulatory caffeine (the control) during four alternating 20-day periods. Trial 1 subjects took their pretrial dextroamphetamine dose at breakfast and lunch. Trial 2 subjects took 10 mg at these times. Subjects recorded the integer from 0 to 3 that represented their headache intensity during the previous 24 hours. The subject's data were the average daily headache grade for the two dextroamphetamine periods and for the two caffeine periods. The differential effect of amphetamine and caffeine on each group of eight subjects and on each individual was analyzed by t-tests.

Results.—In both trials, the tension-type and migraine groups had lower mean daily headache grades in the amphetamine than in the caffeine periods. P values for these differences indicated that there were real drug effects, on the average, in the migraine groups (P < .05) and suggestive but inconclusive effects in the tension-type groups (P < .10). The individual n of 1 analyses showed that five tension-type and three migraine subjects in Trial 1 and three tension-type and three migraine subjects in Trial 2 had considerably lower mean daily headache grades on amphetamine with P values indicating, at various levels of significance (from P < .05 to P < .001), real amphetamine effects. Twelve of the remaining 18 patients had lower, albeit not significant, mean daily grades with amphetamine. No subject in either trial had a significantly lower mean daily headache grade on caffeine.

Conclusions.—Dextroamphetamine had real preventive effects on chronic tension-type and migraine headaches in some subjects. These results should encourage other investigators to study its effects on these headaches.