Neuropsychological effects of valproate in traumatic brain injury - A randomized trial

Objectives: To examine the neuropsychological side effects of valproate (VP A) given to prevent posttraumatic seizures. Methods: In a randomized, doubl e-masked, parallel group clinical trial, we compared the seizure prevention and neuropsychological effects of 1 or 6 months of VPA to 1 week of phenyt oin. We studied 279 adult subjects who were randomized within 24 hours of i njury and examined with a battery of neuropsychological measures at 1, 6, a nd 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 ch anges in treatment. Results: No significant adverse or beneficial neuropsyc hological effects of VPA were detected. Conclusions: Valproate (VPA) appear s to have a benign neuropsychological side effects profile, making it a cog nitively safe antiepileptic drug to use for controlling established seizure s or stabilizing mood. However, based on this study, VPA should not be used for prophylaxis of posttraumatic seizures because it does not prevent post traumatic seizures, there was a trend toward more deaths in the VPA groups, and it did not have positive effects on cognition.