Pregabalin add-on for drug-resistant partial epilepsy

  • Review
  • Intervention




Epilepsy is a common chronic neurological disease with an estimated prevalence of 1% in the UK. Approximately one third of these people continue to have seizures despite drug treatment. In order to try to improve outcomes a number of new antiepileptic drugs have been developed and pregabalin is one of these. This review is an update of a previous Cochrane review (Lozsadi 2008).


To summarise evidence from randomised controlled trials regarding the efficacy and tolerability of pregabalin when used as an add-on antiepileptic drug in treatment-resistant partial epilepsy.

Search methods

We searched the Cochrane Epilepsy Group Specialized Register (May 2012), CENTRAL (the Cochrane Central Register of Controlled Trials issue 5 of 12, The Cochrane Library 2012), MEDLINE (Ovid, 1946 to May week 4 2012) and contacted Pfizer Ltd. (the manufacturers of pregabalin) to identify published, unpublished and ongoing trials.

Selection criteria

We included randomised controlled double-blind trials comparing pregabalin with placebo for people with drug-refractory partial epilepsy. Outcomes included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal for any reason, treatment withdrawal for adverse events and nature of adverse events.

Data collection and analysis

Two review authors (JP and AGM) independently selected and assessed suitable trials and extracted data. Primary analyses were by intention-to-treat (ITT). Results are presented as risk ratios (RR) with 95% confidence intervals (CI).

Main results

Six suitable industry-sponsored trials (2009 participants) were identified and included in the analysis. Trials tested doses of pregabalin ranging from 50 mg/day to 600 mg/day. For the primary outcome, 50% or higher seizure reduction was significantly more likely in patients randomised 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. Pregabalin was significantly associated with seizure freedom (RR 2.59; 95% CI 1.05 to 6.36). Patients were significantly more likely to have withdrawn from pregabalin treatment than placebo treatment for any reason (RR 1.39; 95% CI 1.13 to 1.72) or for adverse effects (RR 2.69; 95% CI 1.88 to 3.86).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. The odds of response doubled with an increase in dose from 300 mg/day to 600 mg/day (OR 2.12; 95% CI 1.76 to 2.54).

Authors' conclusions

Pregabalin, when used as an add-on drug for treatment-resistant partial epilepsy, is significantly more effective than placebo at achieving a 50% or greater seizure reduction and significantly increasing seizure freedom. Results demonstrate efficacy for doses from 150 mg/day to 600 mg/day, with increasing effectiveness at 600 mg doses. The trials included in this review were of short duration and longer-term trials are needed to inform clinical decision making better.

Plain language summary

Pregabalin add-on for drug-resistant partial epilepsy

Use of pregabalin in combination with other antiepileptic drugs can reduce the frequency of seizures, but has some adverse effects.

Approximately one in 400 people have epileptic seizures that continue despite antiepileptic drug treatment. This review summarises data from six trials that included a total of 2009 participants. In addition to their usual antiepileptic drugs, participants were randomised to take pregabalin (an antiepileptic drug) or control drug. Results showed that patients taking pregabalin were two to three times more likely to reduce their seizure frequency by more than 50% than those taking placebo and two to three times more likely to increase seizure freedom over a 12-week interval. Pregabalin was shown to be effective across a range of doses (150 mg to 600 mg) with increasing effectiveness at higher doses. Side effects associated with pregabalin included co-ordination problems, dizziness, sleepiness, and weight gain. There are no data regarding the longer-term effectiveness of pregabalin; this should be investigated in future studies.