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Neuropsychological effects of valproate in traumatic brain injury

A randomized trial

From the Departments of Rehabilitation Medicine (Dr. Dikmen and J.E. Machamer), Neurological Surgery (Drs. Dikmen, Winn, and Temkin), Pharmacy (Dr. Anderson), and Biostatistics (Dr. Temkin), University of Washington, Seattle, WA.

Address correspondence and reprint requests to Dr. Sureyya Dikmen, Department of Rehabilitation Medicine (Box 356490), University of Washington, Seattle, WA 98195-6490; e-mail: dikmen{at}u.washington.edu

OBJECTIVES: To examine the neuropsychological side effects of valproate (VPA) given to prevent post-traumatic seizures.

METHODS: In a randomized, double-masked, parallel group clinical trial, we compared the seizure prevention and neuropsychological effects of 1 or 6 months of VPA to 1 week of phenytoin. We studied 279 adult subjects who were randomized within 24 hours of injury and examined with a battery of neuropsychological measures at 1, 6, and 12 months after injury. We examined drug effects cross-sectionally at 1, 6, and 12 months and longitudinally by examining differential change from 1 to 6 months and from 6 to 12 months as a function of protocol-dictated changes in treatment.

RESULTS: No significant adverse or beneficial neuropsychological effects of VPA were detected.

CONCLUSIONS: Valproate (VPA) appears to have a benign neuropsychological side effects profile, making it a cognitively safe antiepileptic drug to use for controlling established seizures or stabilizing mood. However, based on this study, VPA should not be used for prophylaxis of posttraumatic seizures because it does not prevent posttraumatic seizures, there was a trend toward more deaths in the VPA groups, and it did not have positive effects on cognition.

Key words: Traumatic brain injuries—Valproate—Phenytoin—Neuropsychological side effects—Double-blind method

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