Fluoxetine for migraine prophylaxis: a double-blind trial

Headache. Nov-Dec 1999;39(10):716-9. doi: 10.1046/j.1526-4610.1999.3910716.x.


Selective serotonin reuptake inhibitors have recently been used in the treatment of migraine.

Objective: We studied the safety and efficacy of fluoxetine in the prevention of migraine.

Patients: Between February 1997 and December 1997, we examined 52 patients (33 women) at the Headache Diagnosis and Therapy Service of the Second University of Naples. Ages ranged from 18 to 65 years, and all patients suffered from migraine without aura according to IHS 1988 criteria. The sample was divided into two groups: group A included 32 patients (19 women; mean age, 36.8 years [SD 12.4]) who received fluoxetine at a dosage of 20 mg per day; group B included 20 patients (14 women; mean age, 38.8 years [SD 15.6]) who received placebo.

Methods: Our study was a single-center, randomized, double-blind, parallel study of fluoxetine for the prophylactic control of migraine and consisted of two phases: 30 days of pharmacological wash out and 6 months of therapy with monthly follow-up. Patients were randomly assigned to two groups: A, fluoxetine or B, placebo. At the first visit, patients provided a detailed history and underwent neurological evaluation and a Zung test for depression. No pathological values were revealed. In order to monitor symptomatology, all patients received a form for the calculation of the total pain index at monthly follow-up.

Results: A comparison of the total pain index between basal values (calculated during the period of wash out) and monthly follow-up (calculated monthly during the period of 6 months of the therapy) showed significant reduction (P < .05) beginning from the third month of treatment in the fluoxetine group and no significant reduction in the placebo group.

Conclusion: Even if preliminary and to be confirmed, these data seem to support the use of fluoxetine in the treatment of migraine.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Double-Blind Method
  • Female
  • Fluoxetine / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / prevention & control*
  • Preventive Medicine / methods*
  • Serotonin Uptake Inhibitors / therapeutic use*


  • Serotonin Uptake Inhibitors
  • Fluoxetine