A Study of the Safety, Efficacy, and Tolerability of Switching From the Standard Delayed Release Preparation of Divalproex Sodium to the Extended Release Formulation in Patients With Schizophrenia.

摘要

OBJECTIVE:: To assess the safety, efficacy, and tolerability of switching from a multiple dose preparation of divalproex sodium delayed release (DR) to once-daily dosing with divalproex sodium extended release (ER) in patients with schizophrenia already receiving the standard DR formulation. METHOD:: Thirty subjects with schizophrenia were switched from divalproex DR to a 4-week open-label treatment trial of the ER formulation. Baseline plasma levels of valproate were obtained 12 hours postdose. Patients were converted from divalproex DR to ER on a 1.0:1.0 mg basis (rounded up to the nearest 500-mg increment) if baseline valproate plasma levels were >/=85 microg/mL; otherwise, the conversion rate was 1.0:1.2 mg rounded up. Measured at baseline and end point were the Brief Psychiatric Rating Scale and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale. End point plasma levels were obtained at both 12 and 24 hours postdose. RESULTS:: Patients who switched from divalproex DR to ER had a small (and probably clinically insignificant) improvement noted on the total Brief Psychiatric Rating Scale at end point (mean change +/- SD = -2.3 +/- 5.4; t = -2.2538; df = 28; P = 0.0322) and on the Udvalg for Kliniske Undersogelser (mean change +/- SD = -2.2 +/- 4.1; t = -2.7361; df = 26; P = 0.0111). Baseline and end point trough plasma levels were 80.1 +/- 20.4 and 73.1 +/- 24.2 microg/mL, respectively. Patients who converted on a 1.0:1.0 mg basis had lower end point valproate trough plasma levels than at baseline but did not experience deterioration on their psychopathology. For all patients, end point valproate peak and trough plasma levels were statistically significantly different (t = -3.8706; df = 27; P = 0.0006), but these differences were small in magnitude (mean +/- SD = 14.6 +/- 19.6 microg/mL). Seven patients experienced spontaneously reported adverse events, but none required early termination from the protocol. CONCLUSIONS:: Switching to a once-daily formulation of ER divalproex can be accomplished without a deterioration in psychopathology. The ER formulation of divalproex sodium appears well tolerated. A parallel group design will be necessary to confirm these findings.