Reassessing the lower end of the phenytoin therapeutic range: a review of the literature

OBJECTIVE: To critically review available data on the effective lower end of the phenytoin therapeutic range for the treatment of seizure disorders. DATA SOURCES: Relevant articles were identified from an English-language search of MEDLINE 1982-1992. Additional references were found in bibliographies of these articles. STUDY SELECTION/DATA EXTRACTION: We reviewed articles that included data on serum phenytoin concentrations (SPCs) and seizure control. Data on concurrent anticonvulsants, seizure diagnosis, and seizure severity were extracted when available. DATA SYNTHESIS: The original study defining the phenytoin therapeutic range as 10-20 mg/L is analyzed; it was based on a small, homogeneous sample that cannot be generalized to a more diverse epileptic population. Many studies report patients obtaining seizure control with SPCs below 10 mg/L. Studies including a range of seizure diagnoses and severity have a larger variability in effective SPCs; however, effective SPCs are reproducible. CONCLUSIONS: The therapeutic range of phenytoin is defined on an individual basis. Some patients, especially those with infrequent, primary tonic-clonic seizures, may be controlled with phenytoin concentrations below the recognized reference range of 10-20 mg/L.