This is an updated version of the Cochrane Review previously published in Issue 11, 2016 of the Cochrane Database of Systematic Reviews.

Background

Epilepsy is a common neurological disorder in which abnormal electrical discharges from the brain cause recurrent seizures. We studied two types of epileptic seizures in this review: generalised onset seizures, in which electrical discharges begin in one part of the brain and move throughout the brain; and focal onset seizures, in which the seizure is generated in and affects one part of the brain (the whole hemisphere of the brain or part of a lobe of the brain). Focal seizures may become generalised (secondary generalisation) and move from one part of the brain throughout the brain. For around 70% of people with epilepsy, a single antiepileptic medication can control generalised onset or focal onset seizures.

This review applies to people with focal seizures (with or without secondary generalisation) and people with generalised tonic-clonic seizures, a specific generalised seizure type. This review does not apply to people with other generalised seizure types such as absence seizures or myoclonic seizures, as the recommended treatments for these seizure types are different.

Objective

Carbamazepine and lamotrigine are first-choice treatments for individuals with recently diagnosed epilepsy. The aim of this review was to compare how effective these drugs are at controlling seizures, to find out if they are associated with side effects that may result in individuals stopping the medication, and to inform a choice between these medications.

Methods

The last search for trials was in February 2018. We assessed the evidence from 14 randomised controlled trials comparing lamotrigine with carbamazepine. We were able to combine information for 2572 people from nine of the 14 trials; for the remaining 1215 people from five trials, information was not available to use in this review.

Results

The results of the review suggest that people are more likely to withdraw earlier from carbamazepine than lamotrigine treatment. The most common medicine-related reason for withdrawal was side effects: 52% of total withdrawals in participants on carbamazepine and 36% of total withdrawals in participants on lamotrigine. The second most common medicine-related cause for withdrawal was seizure recurrence: 58 of 719 total withdrawals (8%) on carbamazepine and 105 of 697 total withdrawals (15%) on lamotrigine.

The results suggest that recurrence of seizures after starting treatment with lamotrigine may happen earlier than treatment with carbamazepine. They also suggest that freedom from seizures for a period of six months may occur earlier on carbamazepine than lamotrigine. The majority of the people included in the 14 trials (88%) experienced focal seizures, so the results of this review apply mainly to people with this seizure type.

The most common side effects reported by participants during the trials were dizziness, fatigue, gastrointestinal problems, headaches and skin problems. These side effects were reported a similar number of times by people taking lamotrigine or carbamazepine.

Quality of the evidence

For people with focal onset seizures, we judged the quality of the evidence to be high for the outcomes of seizure recurrence and remission of seizures and we judged the quality of the evidence to be moderate for the outcome of treatment failure. The design of the trials (specifically, whether the people and treating clinicians knew which medication they were taking) may have influenced the rates of withdrawal from treatments. Up to 50% of people in the trials used in our results may have been wrongly classified as having generalised seizures; for people with generalised onset seizures, we judged the quality of the evidence to be moderate for the outcomes of seizure recurrence and remission of seizures and low quality for the outcome of treatment failure.

Conclusions

For people with focal onset seizures, lamotrigine and carbamazepine are effective treatments and a choice between these two treatments must be made carefully. More information is needed for people with generalised onset seizures. We recommend that all future trials comparing these medications, or any other antiepileptic medications, should be designed using high-quality methods. Seizure types of people included in trials should also be classified very carefully to ensure that the results are also of high quality.