Phenytoin: EEG effects and plasma levels in volunteers.

The electroencephalographic (EEG) and behavioral effects of oral doses of phenytoin from 100 mg to 1 g in normal male volunteers were measured. The electroencephalogram exhibited decreases in power in the slow frequencies and increases in the fast frequencies, accompanied by an increase in mean frequency. These changes are similar to those seen with psychostimulants. They occurred at average plasma levels of 8 micrograms/ml and above. The time course and the intensity of EEG effects parallel plasma levels. Drug-related EEG changes were bilaterally symmetric. EEG changes at plasma levels of 8--12 micrograms/ml were not associated with behavioral toxic signs. These findings suggest that future psychiatric studies of phenytoin as a psychostimulant should include monitoring for plasma levels, with a minimum of 8 micrograms/ml as a guide to clinical efficacy.