Memantine in the preventive treatment of refractory migraine

Objectives.-To assess the efficacy and tolerability of memantine (MEM) in the preventive treatment of refractory migraine. Background.-Glutamate is of importance in migraine pathophysiology and may be related to progression from episodic to chronic mirgraine. Furthermore, individuals with chronic pain often report cognitive problems. MEM has the potential to address both issues, justifying this pilot study. Methods.-We included subjects with refractory migraine (episodic migraine with 8-14 days of headache per month or transformed migraine, who had previously failed at least 2 trials of adequate preventive therapy). Other preventive drugs were allowed if the patient had been on a stable dose for more than 30 days. MEM dose ranged from 10 mg to 20 mg per day. The treatment phase lasted 3 months. The primary endpoint was number of days with headache at month 3. Cognitive performance was assessed with the trail making tests A and B (TMT-A and B). Statistical analyses were performed on the intent-to-treat (ITT) population, using data subjected to the last observation carried forward algorithm. We also conducted per protocol analyses. Results.-In the ITT population (n = 28),monthly headache frequency was reduced from 21.8 days at baseline to 16.1 (P<.01) at 3 months. The mean number of days with severe pain was reduced from 7.8 to 3.2 at 3 months (P <.01). The mean disability scores were significantly reduced at 3 months, compared with baseline (36.6 vs 54.9, P<.01). There was a significant reduction in the time to complete TMT-A at termination vs baseline (28.4 vs 23.2, P=.02) and also TMT-B (70.1 vs 50.4, P=.04). Side effects were present in 37.5% of the patients; 5.5% dropped out the study because of poor tolerability. Most adverse events were mild. Conclusion.-This study offers preliminary evidence for the use of MEM in the prevention of refractory migraine. Double-blind studies are now required.