Lamotrigine add-on for drug-resistant partial epilepsy.
BACKGROUND
Epilepsy is a common neurological disorder, affecting almost 0.5 to 1% of the population. Nearly 30% of patients with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review.


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


METHODS
We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2000), MEDLINE (January 1966 to December 1999) and reference lists of articles. We also contacted the manufacturers of lamotrigine (Glaxo-Wellcome).


METHODS
Randomized placebo controlled trials, of patients 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 crossover studies, the first treatment period was treated as a parallel trial.


METHODS
Two reviewers 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), side effects, effects on cognition, and quality of life.


RESULTS
We found three parallel add-on studies and eight cross-over studies, which included 1243 patients (199 children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR (95%CI) for treatment withdrawal (for any reason) is 1.12 (0.78, 1. 61). The 99% CIs for ataxia, dizziness, nausea, and diplopia do not include unity, indicating that they are significantly associated with lamotrigine. 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.


CONCLUSIONS
Lamotrigine add-on therapy is effective in reducing the seizure frequency, in patients 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.
Ramaratnam
S
S
Department of Neurology, Apollo Hospitals, 21 Greams Lane, Off Greams Road, Madras, Tamil Nadu, India, 600006. rsridharan@vsnl.com
Marson
A G
AG
Baker
G A
GA
D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D000077213:Lamotrigine; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D014227:Triazines / Q000008:administration & dosage* / Q000009:adverse effects
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine