Efficacy of the 5-HT1A agonist, buspirone hydrochloride, in migraineurs with anxiety: a randomized, prospective, parallel group, double-blind, placebo-controlled study

OBJECTIVE: To examine the efficacy of buspirone, a 5-HT1A agonist, for migraine combined with anxiety disorder. BACKGROUND: Modulation of the 5-hydroxytryptamine (5-HT) system is used for the neuropharmacology of migraine treatment; however, the involvement of the 5-HT1A system in migraine is not fully understood. METHODS: Seventy-four outpatients aged 20 to 70 years (mean, 46.4; SD, 12.8) were analyzed. All subjects were diagnosed to have migraine according to the International Headache Society criteria and anxiety disorder according to DSM-IV. Subjects were randomly assigned to treatment with either buspirone (10 mg/day) or placebo for 6 weeks. Efficacy variables included changes in headache frequency, headache intensity, Hamilton Anxiety Rating Scale (HAM-A), Headache Self-Efficacy Scale (HMSE), and Headache Disability Inventory (HDI). The correlation between the headache improvement and the anxiolytic effect was analyzed. RESULTS: Headache frequency showed a 43.3% reduction in the buspirone-treated group, but by only 10.3% in the placebo group. HAM-A and HDI were also significantly more lowered in buspirone-treated patients than in placebo-treated patients. However, headache intensity and HMSE score were unchanged. Correlation analysis of the relation between headache frequency reduction and HAM-A improvement, revealed no significant association. CONCLUSIONS: In this study, buspirone showed a prophylactic effect in migraine with anxiety disorder, which was not secondary to its anxiolytic effect. This suggests that the agonistic action for 5-HT1A can be directly effective in migraine prophylaxis. However, more long-term study is warranted before concluding the efficacy.