Pregabalin versus gabapentin in partial epilepsy: a meta-analysis of dose-response relationships

Abstract

Background: To compare the efficacy of pregabalin and gabapentin at comparable effective dose levels in patients with refractory partial epilepsy.

Methods: Eight randomized placebo controlled trials investigating the efficacy of pregabalin (4 studies) and gabapentin (4 studies) over 12 weeks were identified with a systematic literature search. The endpoints of interest were "responder rate" (where response was defined as at least a 50% reduction from baseline in the number of seizures) and "change from baseline in seizure-free days over the last 28 days (SFD)". Results of all trials were analyzed using an indirect comparison approach with placebo as the common comparator. The base-case analysis used the intention-to-treat last observation carried forward method. Two sensitivity analyses were conducted among completer and responder populations.

Results: The base-case analysis revealed statistically significant differences in response rate in favor of pregabalin 300 mg versus gabapentin 1200 mg (odds ratio, 1.82; 95% confidence interval, 1.02, 3.25) and pregabalin 600 mg versus gabapentin 1800 mg (odds ratio, 2.52; 95% confidence interval, 1.21, 5.27). Both sensitivity analyses supported the findings of the base-case analysis, although statistical significance was not demonstrated. All dose levels of pregabalin (150 mg to 600 mg) were more efficacious than corresponding dosages of gabapentin (900 mg to 2400 mg) in terms of SFD over the last 28 days.

Conclusion: In patients with refractory partial epilepsy, pregabalin is likely to be more effective than gabapentin at comparable effective doses, based on clinical response and the number of SFD.

Figure 1

Flow chart for analysis of responders. CI = confidence interval; GBP = gabapentin; PGB = pregabalin

Figure 2

Dose-response curves for pregabalin and gabapentin for response (base-case analysis). The 450 mg pregabalin and 2400 mg gabapentin doses were not studied in any of the trials; the results plotted here were calculated from the dose-response equations. CI = confidence interval

Figure 3

Dose-response curves for pregabalin and gabapentin for response (sensitivity analyses). CI = confidence interval

Figure 4

Dose-response curves for pregabalin and gabapentin for change from baseline in seizure-free days in last 28 days. The 450 mg pregabalin and 2400 mg gabapentin doses were not studied in any of the trials; these results were calculated from the dose-response equations.