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Evidence summaries

Phenobarbitone Vs. Phenytoin for Partial Onset Seizures and Generalized Onset Tonic-Clonic Seizures

Phenytoin may be a more effective drug than phenobarbitone in terms of treatment retention (treatment failures due to lack of efficacy or adverse events or both). There are probably no differences between the drugs in terms of time to seizure recurrence and seizure remission. Level of evidence: "C"

A Cochrane review [Abstract] 1 included 5 studies with a total of 635 subjects. Four of the studies recruited adults and 3 recruited children. Results for the primary outcome of the review were (pooled HR adjusted for seizure type, n=499): time to treatment failure for any reason related to treatment (1.61, 95% CI 1.22 to 2.12), time to treatment failure due to adverse events (1.99, 95% CI 1.37 to 2.87), time to treatment failure due to lack of efficacy (1.87, 95% CI 1.32 to 2.66), showing a statistically significant advantage for phenytoin compared to phenobarbitone. For secondary outcomes, there were no statistically significant differences between phenytoin and phenobarbitone (pooled HR adjusted for seizure type) for time to first seizure post-randomisation (0.85, 95% CI 0.69 to 1.06; n=624), time to 12-month remission (0.90, 95% CI 0.69 to 1.19; n=588), and time to 6-month remission (0.91, 95% CI 0.71 to 1.15; n=588). For individuals with focal onset seizures (73% of individuals contributing to analysis), numerical results were similar and conclusions the same as for analyses of all individuals and for individuals with generalised onset seizures (27% of individuals contributing to analysis), results were imprecise and no clear differences between the drugs were observed.

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment) and imprecise results (few patients in each study).

References

  • Nevitt SJ, Tudur Smith C, Marson AG. Phenobarbitone versus phenytoin monotherapy for epilepsy: an individual participant data review. Cochrane Database Syst Rev 2019;7():CD002217. [PubMed]

Primary/Secondary Keywords