This is an updated version of the Cochrane Review previously published in 2013. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked
seizures. It is believed that with effective drug treatment, up to 70% of individuals with active
epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting
drug therapy with a single
antiepileptic drug in monotherapy.Worldwide,
phenytoin is a commonly used
antiepileptic drug. It is important to know how newer drugs, such as
oxcarbazepine, compare with commonly used standard treatments.
OBJECTIVES: We searched the following databases on 20 August 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane
Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 August 2018), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA: Individual participant data were available for 480 out of a total of 517 participants (93%), from two out of three included trials. For remission outcomes, a HR of less than one indicated an advantage for
phenytoin; and for first seizure and treatment failure outcomes, a HR of less than one indicated an advantage for
oxcarbazepine.The results for
time to treatment failure for any reason related to treatment showed a potential advantage of
oxcarbazepine over
phenytoin, but this was not statistically significant (pooled HR adjusted for
epilepsy type: 0.78 95% CI 0.53 to 1.14, 476 participants, two trials, moderate-quality evidence). Our analysis showed that treatment failure due to adverse events occurred later on with
oxcarbazepine than
phenytoin (pooled HR for all participants: 0.22 (95% CI 0.10 to 0.51, 480 participants, two trials, high-quality evidence). Our analysis of
time to treatment failure due to lack of efficacy showed no clear difference between the drugs (pooled HR for all participants: 1.17 (95% CI 0.31 to 4.35), 480 participants, two trials, moderate-quality evidence).We found no clear or statistically significant differences between drugs for any of the secondary outcomes of the review: time to first seizure post-randomisation (pooled HR adjusted for
epilepsy type: 0.97 95% CI 0.75 to 1.26, 468 participants, two trials, moderate-quality evidence); time to 12-month remission (pooled HR adjusted for
epilepsy type 1.04 95% CI 0.77 to 1.41, 468 participants, two trials, moderate-quality evidence) and time to six-month remission (pooled HR adjusted for
epilepsy type: 1.06 95% CI 0.82 to 1.36, 468 participants, two trials, moderate-quality evidence).The most common adverse events reported in more than 10% of participants on either drug were
somnolence (28% of total participants, with similar rates for both drugs),
headache (15% of total participants, with similar rates for both drugs),
dizziness (14.5% of total participants, reported by slightly more participants on
phenytoin (18%) than
oxcarbazepine (11%)) and gum
hyperplasia (reported by substantially more participants on
phenytoin (18%) than
oxcarbazepine (2%)).The results of this review are applicable mainly to individuals with focal onset
seizures; 70% of included individuals experienced
seizures of this type at baseline. The two studies included in IPD meta-analysis were generally of good methodological quality but the design of the studies may have biased the results for the secondary outcomes (time to first seizure post-randomisation, time to six-month and 12-month remission) as seizure recurrence data were not collected following treatment failure or withdrawal from the study. In addition, misclassification of
epilepsy type may have impacted on results, particularly for individuals with generalised onset
seizures.
AUTHORS' CONCLUSIONS: High-quality evidence provided by this review indicates that treatment failure due to adverse events occurs significantly later with
oxcarbazepine than
phenytoin. For individuals with focal onset
seizures, moderate-quality evidence suggests that
oxcarbazepine may be superior to
phenytoin in terms of treatment failure for any reason, seizure recurrence and seizure remission. Therefore,
oxcarbazepine may be a preferable alternative treatment than
phenytoin, particularly for individuals with focal onset
seizures. The evidence in this review which relates to individuals with generalised onset
seizures is of low quality and does not inform current treatment policy.We recommend that future trials should be designed to the highest quality possible with regards to choice of population, classification of seizure type, duration of follow-up (including continued follow-up after failure or withdrawal of randomised treatment), choice of outcomes and analysis, and presentation of results.