Safety and efficacy of switching psychiatric patients from a delayed-release to an extended-release formulation of divalproex sodium.

Abstract

This study evaluated the safety and efficacy of divalproex sodium extended-release (ER) when patients were switched from therapy with divalproex sodium delayed-release (DR) to divalproex sodium ER. This open-label, 7-day study included 55 patients with bipolar disorder, major depression, schizophrenia, schizoaffective disorder, Alzheimer's disease, dementia, or intermittent explosive disorder. Baseline plasma valproate concentrations were determined, and patients received their usual morning dose of divalproex sodium DR. At 9:00 p.m. the same day, they received divalproex sodium ER at a dose equal to their total daily dose of divalproex sodium DR. Valproate concentrations were monitored, and efficacy was measured with the Positive and Negative Syndrome Scale (PANSS). Side effects were assessed using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale. Valproate concentrations for 52 patients remained within the therapeutic range. Inpatient PANSS scores significantly improved from baseline to final evaluation on all subscales. For the combined inpatient and outpatient populations, a small but statistically significant improvement from baseline to final evaluation was seen for positive, general, and total PANSS subscale scores. At study's end, patients reported a significant decrease in the number and severity of adverse events; 54 of 55 patients elected to continue therapy with once-daily divalproex sodium ER. This study suggests that divalproex sodium ER is at least as effective as the DR formulation for treating patients with psychiatric illness and may be better tolerated. The ER formulation offers the advantage of once-daily dosing, which may help improve compliance.