Abstracts

Fatty acids reduce seizures in animal models, but there is little human data. In a recent randomized trial (Epilepsy and Behavior 2005;7:253-8), patients with intractable epilepsy showed only a transient response. We are reporting the second such trial., Adults with uncontrolled epilepsy (at least 4 seizures/mo) were randomized 1:1, double-blinded, to PUFA (eicosapentanoic acid (EPA) plus docosahexanoic acid (DHA), 2.2 mg/d in a 3:2 ratio) or placebo (mineral oil). Following a 4-wk prospective baseline and 1-wk titration phase, subjects entered a 12-wk treatment period. Quality of life was assessed (QOLIE-31) before and after treatment. Upon completion, subjects had the opportunity to participate in a 1-mo open-label PUFA trial. Nonparametric statistics were used., 27 subjects were randomized; 4 decided not to participate before entering baseline (3 had been randomized to placebo and 1 to PUFA). 2 other subjects, both randomized to placebo, were dropped during baseline, 1 because of noncompliance and the other because of increased seizures. Completers included 12 PUFA subjects (7F, 5M; ages 25-55 (mean 37)), vs 9 on placebo (5F, 4M; ages 22-62 (mean 39)). 10 on PUFA and 6 on placebo had focal epilepsy, while 2 and 3 had generalized epilepsy (cryptogenic/symptomatic in 2 and 1, idiopathic in 2 on placebo). Subjects took from 1 to 3 antiepileptic drugs, with no significant group differences.
2 on placebo vs. 0 on PUFA had [gt]50% decrease in seizure frequency from baseline during the 12-week treatment (p=0.17). Seizure frequency increased 6% on PUFA and decreased 12% on placebo (p=0.21). On the other hand, of 19 subjects completing the 4-wk open-label PUFA trial, 15 experienced fewer seizures than during baseline (p=0.02), 5 by at least 50%; 4 of these 5 had previously been on placebo. QOLIE-31 scores increased an average of 1 point among PUFA subjects, and decreased 6 points among placebo subjects (p=0.23).
PUFA subjects during the randomized trial and all subjects during the open-label phase showed no differences in serum drug concentrations other than lamotrigine, which declined by a mean of 17% among 6 patients., In this trial, PUFA was not superior to placebo as a treatment for intractable epilepsy. Given PUFA[apos]s absence of adverse effects and efficacy in animal models, additional trials of different doses or EPA:DHA ratios could be justified, particularly a longer, larger trial including children as well as adults. Adequate controls will be needed to account for what can be a strong placebo effect., (Supported by CURE Foundation; The General Clinical Research Center of Brigham and Women[apos]s Hospital, supported by the National Center for Research Resources (5M01 RR-02635); Carlson Laboratories, suppliers of the treatment and placebo capsules.)