Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, andcognitive effects

Objective-To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoi n or sodium valproate in patients after craniotomy. Methods-A prospective, stratified, randomised, double blind single centre c linical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were tre ated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg s odium valproate/day. During the study period patients were seen in the outp atient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse ev ents, and drug plasma concentrations were evaluated. Neuropsychological fun ctioning and quality of life were assessed on the last three visits. In cas es of a seizure an EEG was performed, drug plasma concentration assessed, a nd medication subsequently increased. Results-Of the 100 included patients 14 (seven in each group) experienced o ne or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure . Five patients in the phenytoin group and two in the valproate group had t o stop their treatment due to drug related adverse events. Sixty patients c ompleted the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences. Conclusion-For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and val proate prophylaxis. Valproate is an alternative for anticonvulsant prophyla xis in patients after craniotomy.