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Neurobehavioral Effects of Phenytoin and Carbamazepine in Patients Recovering From Brain Trauma: A Comparative Study

Kenneth R. Smith Jr, MD; Peggy M. Goulding, PhD; Diane Wilderman, RN; Peggy R. Goldfader, MA; Patricia Holterman-Hommes; Feifei Wei, PhD
Arch Neurol. 1994;51(7):653-660. doi:10.1001/archneur.1994.00540190029012.
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Objective:  To compare the effects of prophylactic anticonvulsant use of phenytoin and carbamazepine on the cognitive and emotional status of the patient after brain injury.

Design:  Double-blind, placebo-controlled study with assessments before and after withdrawal from drug treatment.

Setting:  Patients had been initially treated by neurosurgeons at a university hospital and were followed up during the study on an outpatient basis.

Patients:  Forty of 64 patients receiving phenytoin and 42 of 127 patients receiving carbamazepine from 6 to 44 months for seizure prophylaxis after brain injury met study criteria and were assigned to continue or discontinue treatment. Groups were balanced for age, sex, race, weight, intelligence, type of injury, duration of therapy, and drug plasma concentration at screening.

Intervention:  A battery of neuropsychological tests was administered twice during a 4-week baseline period, at the end of a 4- to 5-week period of continued drug treatment or placebo, and after 4 weeks of not receiving medication.

Main Outcome Measures:  Attention and concentration, psychomotor speed, memory, verbal fluency, and emotional state.

Results:  No significant differences were found in the performance of patients in medication and placebo groups for either drug at the end of the placebo phase. Patients in the combined groups showed significant improvement (P<.01) on several measures of motor and speeded performance following cessation of drug treatment. Multivariate analyses showed additional differences between phenytoin and carbamazepine and also suggested a significant practice effect on some measures used.

Conclusions:  Both phenytoin and carbamazepine seem to have negative effects on cognitive performance, particularly on tasks with significant motor and speed components. Practice effects were noted and may account for much of the improvement when patients stopped taking the drugs. Overall effects of the drugs were small and of limited clinical significance, but differences among subjects were noted that may affect selection of a particular drug for the individual patient.

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The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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