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Evidence summaries

Pregabalin Add-on for Drug-Resistant Partial Epilepsy

Pregabalin, when used as an add-on drug for treatment-resistant focal epilepsy, appears to be significantly more effective than placebo at producing a 50% or greater seizure reduction and seizure freedom. The efficacy appears to increase at 600 mg doses, however, issues with tolerability were noted at higher doses. Level of evidence: "B"

A Cochrane review [Abstract] 1 included 9 studies with a total of 3327 patients. Median follow-up was 12 weeks.

  • Pregabalin vs. placebo (7 trials): For the primary outcome, patients randomised to pregabalin were significantly more likely to attain a 50% or greater reduction in seizure frequency compared to placebo (RR 2.28, 95% CI 1.52 to 3.42; 7 trials, n=2193). The odds of response doubled with an increase in dose from 300 mg/day to 600 mg/day (OR 1.99, 95% CI 1.74 to 2.28), indicating a dose-response relationship. Pregabalin was significantly associated with seizure freedom (RR 3.94, 95% CI 1.50 to 10.37; 4 trials, n=1125). Patients were significantly more likely to withdraw from pregabalin treatment than placebo for any reason (RR 1.35, 95% CI 1.11 to 1.65; 7 trials, n=2193) and for adverse effects (RR 2.65, 95% CI 1.88 to 3.74; 7 trials, n=2193).
  • Pregabalin vs. active-control drugs (3 trials): Patients allocated to pregabalin were significantly more likely to achieve a 50% or greater reduction in seizure frequency than those allocated to lamotrigine (RR 1.47, 95% CI 1.03 to 2.12; 1 trial, n=293) but not those allocated to levetiracetam (RR 0.94, 95% CI 0.80 to 1.11; 1 trial, n=509) or gabapentin (RR 0.96, 95% CI 0.82 to 1.12; 1 trial, n=484). There were no significant differences between pregabalin and lamotrigine (RR 1.39, 95% CI 0.40 to 4.83) for seizure freedom, however, significantly fewer participants achieved seizure freedom with add-on pregabalin compared to levetiracetam (RR 0.50, 95% CI 0.30 to 0.85). There were no significant differences between pregabalin and lamotrigine (RR 1.07, 95% CI 0.75 to 1.52), levetiracetam (RR 1.03, 95% CI 0.71 to 1.49), or gabapentin (RR 0.78, 95% CI 0.57 to 1.07) for treatment withdrawal due to any reason or due to adverse effects (pregabalin vs. lamotrigine: RR 0.89, 95% CI 0.53 to 1.48; vs. levetiracetam: RR 1.29, 95% CI 0.66 to 2.54; vs. gabapentin: RR 1.07, 95% CI 0.54 to 2.11). Ataxia, dizziness, somnolence, weight gain, and fatigue 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 follow-up time). The quality of evidence is upgraded by a clear dose-response gradient.

    References

    • Panebianco M, Bresnahan R, Hemming K et al. Pregabalin add-on for drug-resistant focal epilepsy. Cochrane Database Syst Rev 2019;7():CD005612. [PubMed]

Primary/Secondary Keywords