An open-label trial of divalproex sodium extended release for pediatric bipolar spectrum disorder in children age 6 - 12 years

Abstract

Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DSM-IV bipolar disorder with divalproex sodium extended release (ER) monotherapy. Severity of mania was assessed weekly with the Young Mania Rating Scale (YMRS). Results: The sample was 8.9 ± 2.0 years of age and predominantly male (83%). At study entry the mean YMRS score was 26.3 ± 4.5. Of the 18 subjects enrolled, 7 (39%) completed the 8 week course. We failed to find a clinically or statistically significant improvement with divalproex sodium ER. Pre-post comparisons at endpoint (LOCF) indicated an average response reduction of 6.1 ± 2.6 in the YMRS to a mean of 20.3 ± 8.1. Weight increased by 1.36 ± 0.7 kg (p = 0.08) from baseline to endpoint. Conclusion. Divalproex sodium ER monotherapy was associated with poor tolerability, was associated with clinically concerning weight gain but had modest therapeutic benefits in the management of symptoms of mania and depression in children with pediatric bipolar disorder

In Memoriam: Professor Joseph Biederman’s Contributions to Child and Adolescent Psychiatry

“…Our group performed a series of clinical trials for the treatment of pediatric bipolar disorder, examining the effectiveness of second-generation antipsychotics (olanzapine, risperidone, aripiprazole, quetiapine, ziprasidone, and paliperidone; Biederman, McDonnell, Wozniak, Spencer, et al, 2005; Biederman, Mick, Hammerness, Harpold, et al, 2005; Biederman, Mick, Wozniak, Aleardi, Spencer, & Faraone, 2005; Biederman, Mick, Faraone, et al, 2006; Biederman, Mick, Spencer, Dougherty, Aleardi, & Wozniak, 2007; Biederman, Mick, Spencer, Doyle, Joshi, et al, 2007; Frazier et al, 1999; Joshi, Petty, Wozniak, Faraone, et al, 2013; Joshi, Petty et al, 2012; Tohen et al, 2007; Wozniak et al, 2009) as well as anticonvulsants (valproic acid, carbamazepine, and lamotrigine; Biederman, Joshi, Mick, Doyle, et al, 2010; Joshi, Wozniak, Mick, Doyle, et al, 2010; Wozniak, Faraone, Martelon, et al, 2012; Wozniak, Hammerness et al, 2012) and complementary and alternative treatments (Wozniak et al, 2007, 2015; Wozniak, DiSalvo, Farrell, Vaudreuil, Uchida, Ceranoglu, et al, 2022; Wozniak, Farrell, DiSalvo, et al, 2022). These open label trials, some of which included pre-school aged children, provided an early evidence base for addressing symptoms of mania in these severely impaired children.…”