A Cochrane review included 6 studies with a total of 2009 subjects. Participants were taking between one and four AEDs and had at least three partial seizures per month in the pre-randomization baseline period. Trials tested doses of pregabalin ranging from 50 mg to 600 mg per day, the follow-up for all trials was 12 weeks. For the primary outcome, 50% or higher seizure reduction was significantly more likely in patients randomized to pregabalin than to placebo (RR 2.61; 95% CI 1.70 to 4.01). A dose response analysis suggested increasing effect with increasing dose. Results demonstrate efficacy for doses from 150 mg/day to 600 mg/day, with increasing effectiveness at 600 mg doses. Pregabalin was significantly associated with seizure freedom (RR 2.59; 95% CI 1.05 to 6.36). Patients were significantly more likely to have pregabalin withdrawn for any reason (RR 1.39; 95% CI 1.13 to 1.72) or for adverse effects (RR 2.69; 95% CI 1.88 to 3.86). Ataxia, dizziness, somnolence and weight gain were significantly associated with pregabalin.
Comment: The quality of evidence is downgraded by potential reporting bias (all trials financed by the manufacturer) and by indirectness (short duration of trials). The quality of evidence is upgraded by a clear dose-response gradient.