Divalproex sodium in the treatment of pediatric psychiatric disorders

Abstract

Divalproex sodium is an anticonvulsant that is used extensively in adults with indications for epilepsy, acute mania and migraine prophylaxis. It has been used in children and adolescents as a first-line agent for mania in bipolar disorder. Its efficacy as a mood stabilizer has been established, and there have been studies outlining its efficacy as an agent effective in the treatment of conduct disorder, disruptive behavior disorders, aggression and explosive disorder. Longer-acting formulations are now available that cause less gastrointestinal side effects and can also be taken once a day, thus potentially increasing adherence, an important factor in this patient population. Future directions would include developing a more potent valproic acid formulation with fewer side effects, completing randomized controlled trials to establish the efficacy of divalproex sodium in various other pediatric psychiatric disorders, establishing the relative efficacy of the compound in head-to-head comparisons with other mood stabilizers, examining systematically the value of the compound in multimodal pediatric psychiatric treatment packages, and complete effectiveness trials that demonstrate the short- and long-term effectiveness of the compound in the real world of clinicians. In this drug profile, divalproex sodium and its uses in the pediatric population for psychiatric conditions are reviewed.

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

“…An extended release formulation of divalproex sodium is available. By minimizing sharp fluctuations between peaks and troughs in serum concentration of divalproex sodium administered b.i.d., this once a day formulation may improve tolerabil-ity as well as adherence [16]. In the double blind conditions of divalproex sodium extended release, a treatment effect was not observed and adverse events were similar to those observed with placebo [17].…”

Divalproex Sodium for the Treatment of PTSD and Conduct Disordered Youth: A Pilot Randomized Controlled Clinical Trial

“…Study participants were all males from one particular campus, which tends to treat the youngest offender group in the California Youth Authority. The average length of stay at time of participation in the study was 3 months (range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. From this sample of 71 youth, 12 subjects (Mean age = 15.9 years, SD = 1.1, ethnicity = more whites, few minorities) had active ongoing PTSD as established by the open managing clinician according to the PDI-R [21] and had completed all study variables.…”

“…side effects) of sodium valproate and valproic acid [18], are effective in the treatment of PTSD in adults. However, for psychiatric applications in underage populations, the majority of studies using DVP addressing any diagnosis have been neither blinded nor controlled; nevertheless, the medication is extensively prescribed ''off-label'' in youths of all ages for psychiatric targets such as aggression and mania [19].…”

Evidence for Interventions for Young Offenders

“…Two classes of medication, however, deserve mention because of their recent and emerging data. Research indicates that anti‐convulsants (Khanzode et al., 2006; Rana et al., 2005; Saxena et al., 2005; Steiner et al., 2003) and atypical antipsychotics (Findling et al., 2005; Pappadopulos et al., 2003; Schur et al., 2003) appear to show early efficacy and potential for helping RADI youth to gain better control of their behaviours. Consensus guidelines exist for the use of these agents in the treatment of aggression and conduct disorder (Pappadopulos et al., 2003; Steiner, 1997; Steiner & Dunne, 1997).…”