Lamotrigine vs Carbamazepine Monotherapy for Epilepsy Treatment

Lamotrigine vs Carbamazepine Monotherapy for Epilepsy Treatment

Lamotrigine vs Carbamazepine Monotherapy for Epilepsy Treatment


Is lamotrigine or carbamazepine more effective as first-line treatment for epilepsy?


A systematic review of 14 trials, but data was available for only 2,572 people in nine of the trials.


Epilepsy is a neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions associated with abnormal electrical activity in the brain. Focal onset seizures are those generated in and affecting one part of the brain, and generalized onset seizures are those that begin in one part of the brain and move throughout the brain.

Evidence suggests that up to 70% of people with active epilepsy may achieve long-term remission shortly after starting drug therapy. Thus, the choice of first-line drug therapy is crucial. Antiepileptic drugs suppress seizures by reducing neuronal excitability. Lamotrigine, a second-generation antiepileptic drug, and carbamazepine, widely used for over 30 years, are broad-spectrum antiepileptics. Both are recommended by the National Institute for Health and Care Excellence as first-line treatment for new-onset focal seizures and as second-line treatment for generalized onset tonic–clonic seizures. Evaluating the time to treatment failure, remission, and first seizure for both drugs was the goal of this review.


This review included randomized controlled trials involving adults or children with focal onset seizures or generalized onset tonic–clonic seizures, with or without other generalized seizure types. The primary outcomes were time to treatment failure for any treatment-related reason, such as noncompliance; time to treatment failure due to adverse events; and time to treatment failure due to lack of efficacy, such as continued seizures. The secondary outcomes included time to first seizure; time to achieve a six-month, 12-month, and 24-month remission; and incidence of adverse events.

The authors reported a significant advantage of lamotrigine over carbamazepine in terms of time to treatment failure for any treatment-related reason or because of adverse events; however, no difference was noted between the drugs for time to treatment failure due to lack of efficacy.

A significant advantage was noted in the use of carbamazepine compared with lamotrigine for the secondary outcomes of time to first seizure and time to achieve six-month remission. There were no differences between the drugs for the outcomes time to 12-month and 24-month remission; however, the authors cautioned that the evidence was based on only two trials. The rate and types of adverse events were consistent for both drugs and included dizziness, fatigue, gastrointestinal disturbances, headache, and skin problems.


The authors found that lamotrigine is likely to be more effective than carbamazepine in the treatment of new-onset focal seizures (moderate-quality evidence). However, they also found that earlier remission and later seizure recurrence are more likely with carbamazepine compared with lamotrigine (high-quality evidence).


It’s important that future trials be long enough to measure the long-term effectiveness of antiepileptic drugs (treatments will be lifelong for many people with epilepsy), as well as psychosocial, quality-of-life, and health economic outcomes. The International League Against Epilepsy recommends that monotherapy trials should have a primary outcome of time to treatment failure and should last 48 weeks to allow for assessment of longer-term outcomes, such as remission.

Nevitt SJ, et al. Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual participant data review. Cochrane Database Syst Rev 2018;6:CD001031.
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