Lamotrigine add-on for drug-resistant partial epilepsy

Ramaratnam S, Marson AG, Baker GA

Published Online:

May 12, 2010

Lamotrigine in combination with other antiepileptic drugs (add-on) can reduce seizures, but with some adverse effects.

Nearly a third of people with epilepsy continue to have seizures despite treatment with presently used (older) antiepileptic drugs (AEDs). The older AEDs also have adverse effects. As a result a range of new AEDs has been developed as 'add-on' treatments. Lamotrigine is one of these. We found that for people who have drug-resistant partial epilepsy, use of lamotrigine in combination with other AEDs can decrease seizures further. There is also an increase in adverse effects such as unsteadiness (ataxia), dizziness, nausea and double vision (diplopia). More research is needed to determine how this drug compares with other newer AEDs.

Abstract (click to read)

Background:

This is an updated version of the original Cochrane review published in Issue 3, 2000.

Epilepsy is a common neurological disorder, affecting almost 0.5% to 1% of the population. Nearly 30% of people with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review.

Objectives:

To examine the effects of lamotrigine on seizures, adverse effects, cognition and quality of life, when used as an add-on treatment for people with drug-resistant partial epilepsy.

Search strategy:

We searched the Cochrane Epilepsy Group Specialised Register (January 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2010), MEDLINE (1950 to January 2010) and reference lists of articles. We also contacted the manufacturers of lamotrigine (GlaxoSmithKline).

Selection criteria:

Randomized placebo controlled trials, of people with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomization was used. The studies may be double, single or unblinded. For cross-over studies, the first treatment period was treated as a parallel trial.

Data collection and analysis:

Two review authors independently assessed the trials for inclusion and extracted data. Primary analyses were by intention-to-treat. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), adverse effects, effects on cognition, and quality of life.

Main results:

We found four parallel add-on studies, one parallel add-on study with responder enriched design in infants and eight cross-over studies, which included 1524 participants (38 infants, 199 children and 1287 adults). The overall Peto odds ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.51 (95% CI 1.86 to 3.4) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR for treatment withdrawal (for any reason) is 1.13 (95% CI 0.83 to 1.54). The adverse events significantly associated with lamotrigine were: ataxia, dizziness, nausea, somnolence and diplopia. The limited data available preclude any conclusions about effects on cognition and quality of life, though there may be minor benefits in affect balance (happiness) and mastery.

Authors' conclusions:

Lamotrigine add-on therapy is effective in reducing the seizure frequency, in people with drug-resistant partial epilepsy. Further trials are needed to assess the long-term effects of lamotrigine, and to compare it with other add-on drugs.Two new trials have been included in this update, but the conclusions are unchanged.

This record should be cited as:

Ramaratnam S, Marson AG, Baker GA. Lamotrigine add-on for drug-resistant partial epilepsy. Cochrane Database of Systematic Reviews 2001, Issue 3. Art. No.: CD001909. DOI: 10.1002/14651858.CD001909

Assessed as up to date:

January 21, 2010

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Primary Review Group:

Epilepsy Group

Health topics:

Neurology > Epilepsy > Drugs for broad populations

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Lamotrigine add-on for drug-resistant partial epilepsy

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