Pregabalin add-on for drug-resistant partial epilepsy.

Abstract

BACKGROUND:

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 (Pulman 2008); no further studies have been added since the previous update in 2012 and only one study has been identified as an ongoing trial.

OBJECTIVES:

To summarise evidence from randomised controlled trials regarding the efficacy and tolerability of pregabalin when used as an add-on antiepileptic treatment in drug-resistant partial epilepsy. The definitions of drug resistance used were those employed by the authors of the included trials.

SEARCH METHODS:

We searched the Cochrane Epilepsy Group Specialized Register (Jan 2014), CENTRAL (the Cochrane Central Register of Controlled Trials, The Cochrane Library 2013, Issue 12), MEDLINE (Ovid, 1946 to 09/01/2014) and contacted Pfizer Ltd. (the manufacturers of pregabalin) to identify published, unpublished and ongoing trials.

SELECTION CRITERIA:

We included randomised controlled trials comparing pregabalin with placebo or an alternative antiepileptic drug for people with drug-resistant 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). Included studies were assessed for risk of bias by two authors using the Cochrane 'Risk of bias' tool.

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). Overall, the evidence was rated as low/unclear risk of bias due to the possibility of publication bias. The quality of the evidence was rated as moderate using the GRADE approach.

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.

• Authors: Jennifer Pulman, Karla Hemming, Anthony G Marson
• Journal: The Cochrane database of systematic reviews (Cochrane Database Syst Rev) Issue 3 Pg. CD005612 (Mar 12 2014) ISSN: 1469-493X [Electronic] England
• PMID: 24623260 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review, Systematic Review)

Chemical References

• Anticonvulsants
• Pregabalin
• gamma-Aminobutyric Acid

Topics

• Anticonvulsants (adverse effects, therapeutic use)
• Drug Resistance
• Epilepsies, Partial (drug therapy)
• Humans
• Pregabalin
• Randomized Controlled Trials as Topic
• gamma-Aminobutyric Acid (adverse effects, analogs & derivatives, therapeutic use)