A Cochrane review included 11 studies with a total of 1401 patients with drug resistant partial epilepsy. The trials tested topiramate doses from 200 to 1000 mg per day vs. placebo. Baseline phases ranged from 4 to 12 weeks and double-blind phases from 11 to 19 weeks. The RR for a 50% or greater reduction in seizure frequency was 2.97 (95% CI 2.38 to 3.72; 11 trials, n=1401). Dose regression analysis shows increasing effect with increasing dose, but found no advantage for doses over 300 or 400 mg per day. The RR for seizure freedom was 3.41 (95% CI 1.37 to 8.51; 5 trials, n=633). The RR for treatment withdrawal was 2.44 (95% CI 1.64 to 3.62; 10 trials, n=1315). The RRs for the following side effects indicate that they are significantly associated with topiramate: ataxia 2.29 (99% CI 1.10 to 4.77; 4 trials, n=757); concentration difficulties 7.81 (2.08 to 29.29); dizziness 1.54 (99% CI 1.07 to 2.22; 6 trials, n=702); fatigue 2.19 (99% CI 1.42 to 3.40; 9 trials, n=1178); paraesthesia 3.91 (1.51 to 10.12; 6 trials, n=822); somnolence 2.29 (99% CI 1.49 to 3.51; 8 trials, n=1813); 'thinking abnormally' 5.70 (99% CI 2.26 to 14.38; 6 trials, n=640) and weight loss 3.47 (1.55 to 7.79; 8 trials, n=821).
Comment: The quality of the evidence is downgraded by indirectness of evidence (short follow-up time).
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