Phenytoin Versus Valproate Monotherapy for Partial Onset Seizures and Generalized Onset Tonic-Clonic Seizures

A Cochrane review [Abstract] 1 included 5 studies with a total of 669 subjects. Results apply to partial onset seizures (simple, complex and secondary generalised tonic-clonic seizures), and generalised tonic-clonic seizures, but not other generalised seizure types (absence or myoclonus seizure types). For remission outcomes: HR > 1 indicates an advantage for phenytoin; and for first seizure and withdrawal outcomes: HR > 1 indicates an advantage for valproate.The main overall results (pooled HR adjusted for seizure type) were time to: (a) withdrawal of allocated treatment 1.09 (95% CI 0.76 to 1.55); (b) achieve 12-month remission 0.98 (95% CI 0.78 to 1.23); (c) achieve six-month remission 0.95 (95% CI 0.78 to 1.15); and (d) first seizure 0.93 (95% CI 0.75 to 1.14). The results suggest no overall difference between the drugs for these outcomes. We did not find any statistical interaction between treatment and seizure type (partial versus generalised).

There was no evidence supporting the policy of using valproate in generalized tonic-clonic seizures and phenytoin in partial onset seizures.

Comment: The quality of evidence is downgraded by inconsistency (heterogeneity in patients: children and adults) and indirectness (differences in seizure types).

References

• Nolan SJ, Marson AG, Weston J et al. Phenytoin versus valproate monotherapy for partial onset seizures and generalised onset tonic-clonic seizures: an individual participant data review. Cochrane Database Syst Rev 2016;(4):CD001769. [PubMed]