Usage of extended-release Depakote has widened in the USA with new approval for treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. Approximately 2.3 million American adults have bipolar disorder.

“Successful treatment for mania depends upon maintaining steady levels of medication in the blood throughout the day,” said Charles Bowden, MD, Professor of Psychiatry and Pharmacology, University of Texas Health Center at San Antonio. “Depakote extended-release produces consistent concentrations of medication throughout a 24-hour period.”

Approval for the new use was based on a randomized, double-blind, placebo-controlled parallel group, three-week, multi-center study. The primary efficacy measurement was the Mania Rating Scale (MRS) total score evaluated as the mean change from baseline to Day 21.

Extended-release Depakote (Depakote ER) was significantly more effective than placebo in reduction of the total score (mean change of -11.5 vs. -9.0 with placebo). In Depakote ER acute mania trials, adverse events with a frequency of greater than 5 percent and at least twice as frequent as those seen with placebo were dyspepsia (23 percent vs. 11 percent), vomiting (13 percent vs. 5 percent), and abdominal pain (10 percent vs. 5 percent).

As with other valproate formulations, Depakote ER should not be administered to patients with hepatic disease or significant hepatic dysfunction. Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives, usually during the first six months of treatment. Concomitant administration of valproic acid and topiramate has been associated with hyperammonemia with and without encephalopathy.

The frequency of adverse effects, particularly elevated liver enzymes and
thrombocytopenia, may be dose-related.