Efficacy of gabapentin in migraine prophylaxis

Objective.-To compare gabapentin with placebo for use as a prophylactic age nt in patients with migraine (with or without aura). Study Design and Treatment.-After screening, a 4-week, single-blind, placeb o baseline period was followed by a 12-week, double-blind, treatment period . The 12-week treatment period consisted of a 4-week titration phase and an 8-week stable-dosing phase. During the 4-week titration phase, patients we re started on one 300-mg capsule of gabapentin or matching placebo. Patient s were titrated weekly from 900 mg/day (end of week 1) to 2400 mg/day (end of week 4) and had to be receiving a stable dose of study medication by the end of the titration period. Study medication was to be given on a three-t imes-a-day dosing regimen. Methods.-The study hypothesis was defined a priori as a lower 4-week migrai ne rate during the second stabilization period for the gabapentin-treated p atients as compared with the placebo-treated patients. The analyses were pe rformed with the 4-week migraine rate at baseline as a covariate and center as a blocking factor. Results.-At seven participating centers, 143 patients with migraine were ra ndomized in a 2:1 ratio and received either gabapentin (n = 98) or matching placebo (n = 45). Thirty-three patients (24.1%) discontinued prematurely f rom the study, including 24 (24.5%) of 98 gabapentin-treated patients and 9 (20.0%) of 45 placebo-treated patients; the majority of patients discontin ued due to adverse events (16 [16.3%] of 98 gabapentin-treated patients; 4 [8.9%] of 45 placebo-treated patients). Patients included in the analysis w ere evenly balanced for age, sex, race, weight, and height. The majority of these patients were white (80 [92.0%] of 87) and women (72 [82.8%] of 87), with a mean age of approximately 39.4 years and a history of migraine epis odes for a mean of about 21 years. At the end of the 12-week treatment phas e, the median 4-week migraine rate was 27 for the gabapentin-treated patien ts maintained on a stable dose of 2400 mg/day and 3.5 for the placebo-treat ed patients (P = .006), compared with 4.2 and 4.1, respectively, during the baseline period. Additionally, 26 (46.4%) of 56 patients receiving a stabl e dose of 2400 mg/day gabapentin and 5 (16.1%) of 31 patients receiving pla cebo showed at least a 50% reduction in the 4-week migraine rate (P = .008) . The average number of days per 4 weeks with migraine was also statistical ly significant and favored gabapentin (P = .006) during stabilization perio d 2. The median change in 4-week headache rate was statistically significan t as wed (P = .013). The most frequently reported adverse events for both t reatment groups,were asthenia, dizziness, somnolence and infection. Adverse events determined by the investigator to be associated with study drug res ulted in patient,withdrawal in 13 (13.3%) of 98 gabapentin-treated patients and 3 (6.7%) of 45 placebo-treated patients. Somnolence and dizziness acco unted for many of the premature withdrawals among those taking gabapentin. Conclusion.-Gabapentin is an effective prophylactic agent for patients with migraine. In addition, gabapentin appears generally well tolerated with mi ld to moderate somnolence and dizziness.