Abstracts

Divalproex sodium (Depakote[reg]) is an effective anticonvulsant, anti-manic, and migraine prophylaxis agent. Recently, a new extended-release formulation of divalproex sodium became available which allows for once-daily dosing and provides prolonged therapeutic serum levels. Divalproex sodium extended-release (Depakote ER[reg]) is indicated for the treatment of various seizure types and for the prophylaxis of migraine headaches. Many investigators are conducting their own small-scale studies to evaluate the safety and efficacy of this improved formulation.
A review of Med-Line and abstract booklets from neurology symposia, identified five presented and/or published clinical trials which evaluated the safety and efficacy of converting a total of 212 epilepsy patients from the delayed-release formulation of divalproex to the new, extended-release formulation (Zielinski and Smith, [italic]Epilepsia[/italic] 42 Suppl 7: 92 (Abstract 1.291), 2001; McCabe et al., [italic]Epilepsia[/italic] 42 Suppl 7: 90 (Abstract 1.284), 2001; Thompson et al., [italic]Epilepsia[/italic] 42 Suppl 7: 87 (Abstract 1.273), 2001; Thibault et al., [italic]Epilepsy Res[/italic] 50: 243-249, 2002; and Uthman et al. Fifth Europ Congr of Epileptology, Madrid, Spain, 2002). This meta-analysis conducted risk assessments comparing the rates of reported side effects and seizures in these studies.
Prior to conversion the mean dose of delayed-release divalproex was 1620 mg (range: 500-4500 mg), and after the conversion the mean dose of extended-release divalproex was 1800 mg (range: 500-5000 mg). A risk assessment analyzing the reported adverse events in each of the five trials indicated that the relative risk of an adverse event while being treated with the extended-release formulation of divalproex was 40% lower than while being treated with the delayed-release formulation (p=0.025). Two of the five trials reported comparative seizure rates, and when analyzed by logistic regression for paired data, indicated that significantly fewer patients experienced seizures while being treated with the extended-release formulation (19%) than while being treated with the delayed-release formulation (39%; p = 0.02).
Extended-release divalproex is equally or more effective than the delayed-release divalproex in controlling seizures, and is significantly better tolerated. Although the results of this analysis are limited by the open-label, and in many cases, retrospective nature of the studies included in this meta-analysis, the results presented here do demonstrate the improved tolerability and efficacy of the extended-release formulation of divalproex sodium as evaluated by several clinicians in a naturalistic setting. The improved efficacy may be due to better patient compliance, and fewer sub-therapeutic serum concentrations. Likewise, the improved tolerability may be due to fewer supra-therapeutic serum concentrations, and will also likely aid in improved patient compliance.
[Supported by: Abbott Laboratories]