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Evidence summaries

Topiramate Add-on for Drug-Resistant Partial Epilepsy

Topiramate appears to be effective as an add-on treatment for drug-resistant focal epilepsy. It appears to be three times more effective than placebo in reducing seizures at least in a short term, but is associated with side effects. Level of evidence: "B"

Summary

A Cochrane review [Abstract] 1 included 12 studies with a total of 1650 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 2.71 (95% CI 2.05 to 3.59; 12 trials, n=1650). Dose regression analysis showed increasing effect with increasing topiramate dose demonstrated by an OR of 1.45 (95% CI 1.28 to 1.64) per 200 mg/d increase in topiramate dosage. The proportion of patients achieving seizure freedom was also significantly increased with add-on topiramate vs. placebo (RR 3.67, 95% CI 1.79 to 7.54; 8 studies, n=1177). Treatment withdrawal was significantly higher for add-on topiramate vs. placebo (RR 2.37, 95% CI 1.66 to 3.37; 12 studies, n=1650). 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 2.08 (99% CI 1.37 to 3.15; 9 trials, n=1092); paraesthesia 3.65 (1.58 to 8.39; 7 trials, n=1071); somnolence 2.44 (99% CI 1.61 to 3.68; 9 trials, n=1462); 'thinking abnormally' 5.70 (99% CI 2.26 to 14.38; 4 trials, n=640) and weight loss 3.99 (1.82 to 8.72; 9 trials, n=1070).

Comment: The quality of the evidence is downgraded by indirectness of evidence (short follow-up time).

Clinical comments

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    References

    • Bresnahan R, Hounsome J, Jette N et al. Topiramate add-on therapy for drug-resistant focal epilepsy. Cochrane Database Syst Rev 2019;10():CD001417. [PubMed]

Primary/Secondary Keywords