Therapeutic levels of valproate for psychosis

Valproic acid was added to the treatment regimens of 21 psychiatric inpatients whose response to antipsychotic medications had been inadequate, and steady-state serum valproate levels were obtained on 15. The 7 patients who had unequivocal positive therapeutic responses to valproate improved at a mean serum level of 68, with a 95 percent confidence interval of 50 to 86. The 8 nonresponders had a mean serum level of 37.5 with a 95 percent confidence interval of 13 to 62. There was a weak relationship between oral dose and serum level. Two patients never reached therapeutic levels in spite of oral daily dosages of 5 g and 6 g respectively. Therapeutic levels could not be reached by 7 patients (47%) who were taking more than 1,250 mg daily. Our results suggest that the therapeutic serum range for seizures is valid for psychiatric patients but that the usual suggested oral dosage is often inadequate. Drug interactions may account for this.