Amitriptyline versus amitriptyline combined with fluoxetine in the preventative treatment of transformed migraine: a double-blind study.

Background and Objectives: Antidepressants are often used to treat chronic daily headache disorders such as transformed migraine, in part because of the high prevalence of associated mood disorder. We conducted this study to evaluate the efficacy and tolerability of combined treatment with amitriptyline and fluoxetine compared with amitriptyline alone for chronic daily headache due to transformed migraine.
Patients and Methods: Thirty-nine patients, 26 women and 13 men, aged 20 to 69 years (mean, 36.4; SD, 2.5) who fulfilled criteria for transformed migraine proposed by Silberstein et al were studied prospectively. Amitriptyline was dosed as follows: 8 mg/day for 6 days, 8 mg twice a day for 6 days, 20 mg/day for 6 days, and 20 mg twice a day for 45 days. In the group receiving combination therapy, fluoxetine was dosed and administered identically. The initial and end of the study (9 weeks) headache indices (frequency x intensity) were compared between groups.
Results: Twenty-seven patients completed the study, 13 in the amitriptyline-alone group (group 1) and 14 in the combination-therapy group (group 2). The most frequent adverse event in both groups was dry mouth, and there was no significant difference in the occurrence of this or other adverse events between the two groups. Initial headache indices were similar for groups 1 and 2. The mean difference between the initial and final headache index for group 1 was 513.5 (P<.0005) and 893 (P<.0017) for group 2. The difference between the final headache index for the two groups was not significant (P>.207).
Conclusions: We were unable to demonstrate any significant benefit from amitriptyline plus fluoxetine over amitriptyline alone in the treatment of chronic daily headache/transformed migraine. Because of the small number of subjects involved and the short duration of our study, a type II error cannot be excluded.