Divalproex treatment for youth with explosive temper and mood lability: A double-blind, placebo-controlled crossover design

Columbia University, New York, New York, United States
American Journal of Psychiatry (Impact Factor: 12.3). 06/2000; 157(5):818-20. DOI: 10.1176/appi.ajp.157.5.818
Source: PubMed


The authors sought to replicate open-label findings showing that specific criteria for explosive temper and mood lability identify disruptive youth who improve while receiving the anticonvulsant divalproex sodium.
Twenty outpatient children and adolescents (ages 10-18) with a disruptive behavior disorder (oppositional defiant disorder or conduct disorder) met the specific criteria for explosive temper and mood lability. They received 6 weeks of divalproex treatment and 6 weeks of placebo by random assignment. Independent evaluators blind to group assignment assessed response at the end of each phase.
At the end of phase 1, eight of 10 subjects had responded to divalproex; zero of 10 had responded to placebo. Of the 15 subjects who completed both phases, 12 has superior response taking divalproex.
This preliminary study replicates open-label findings showing that divalproex is an efficacious treatment for explosive temper and mood lability in disruptive children and adolescents.

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    • "They are also already suggesting means of influencing these dispositions in ways that might be thought conducive to rehabilitation in some offenders. For example, some widely used antidepressants have recently shown promise in reducing aggression, while the drug divalproex has been found to reduce impulsiveness in adolescents with explosive temper (Bond 2005; Nevels et al. 2010; Donovan 2000; Khanzode et al.2006). "
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    The Journal of Ethics 06/2014; 18(2):101-122. DOI:10.1007/s10892-014-9161-6
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    • "Lithium was the first mood stabilizer shown to be effective in reducing aggressive behavior in children with CD in the 1980s [17-19], though at least one trial found no difference from placebo over two weeks [20]. Methodologically rigorous studies of divalproex found it to be superior to placebo in treating explosive temper and mood lability [21] and CD [22] in adolescents. Both divalproex and lithium require vigilant blood monitoring, which is unappealing to many patients and professionals. "
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    ABSTRACT: Polypharmacy (the concurrent use of more than one psychoactive drug) and other combination interventions are increasingly common for treatment of severe psychiatric problems only partly responsive to monotherapy. This practice and research on it raise scientific, clinical, and ethical issues such as additive side effects, interactions, threshold for adding second drug, appropriate target measures, and (for studies) timing of randomization. One challenging area for treatment is severe child aggression. Commonly-used medications, often in combination, include psychostimulants, antipsychotics, mood stabilizers, and alpha-2 agonists, which vary considerably in terms of perceived safety and efficacy. In designing our NIMH-funded trial of polypharmacy, we focused attention on the added benefit of a second drug (risperidone) to the effect of the first (stimulant). We selected these two drugs because their associated adverse events might neutralize each other (e.g., sleep delay and appetite decrease from stimulant versus sedation and appetite increase from antipsychotic). Moreover, there was considerable evidence of efficacy for each drug individually for the management of ADHD and child aggression. The study sample comprised children (ages 6-12 years) with both diagnosed ADHD and disruptive behavior disorder (oppositional-defiant or conduct disorder) accompanied by severe physical aggression. In a staged sequence, the medication with the least problematic adverse effects (stimulant) was openly titrated in 3 weeks to optimal effect. Participants whose behavioral symptoms were not normalized received additional double-blind medication, either risperidone or placebo, by random assignment. Thus children whose behavioral symptoms were normalized with stimulant medication were not exposed to an antipsychotic. All families participated in an empirically-supported parent training program for disruptive behavior, so that the actual comparison was stimulant+parent training versus stimulant+antipsychotic+parent training. We hope that the resolutions of the challenges presented here will be useful to other investigators and facilitate much-needed research on child psychiatric polypharmacy. NCT00796302.
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    • "Plusieurs e ´ quipes ont montré leur inté rêt, notamment la fluoxé tine [4] et le citalopram [15]. Selon les ré sultats de deux e ´ tudes randomisé es, le divalproate de sodium serait efficace dans la prise en charge de l'impulsivité et l'hostilité aussi bien chez les adolescents que chez les adultes [5] [7]. Hollander et al. [8] ont publié e ´ galement les ré sultats d'une e ´ tude multicentrique randomisé e dans laquelle ils ont e ´ tudié la dimension d'agressivité dans trois pathologies : les troubles de la personnalité du cluster B, les troubles explosifs intermittents et le syndrome de stress post-traumatique. "
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    ABSTRACT: Drug treatment of personality disorders is less developed than are psychological treatments in this area, but they are a logical prolongation of psychobiological models of personality and temperament, and respond to the need of many clinicians in front of difficult patients. The results obtained in the field of pharmacotherapy of personality disorders can be classified according to DSM-IV axis-II categorization. In anxious personalities (clusterC), some isolated studies suggest a favourable effect of antidepressants on obsessive-compulsive dimension, on avoidant personality disorder, and on inhibition and trait-anxiety, especially when serotoninergic agents are used. Few studies have been conducted in cluster A personality disorders, and some are in favour of the interest of low doses of antipsychotic drugs in this group. Most studies have been conducted in cluster B, and especially in antisocial and borderline personality disorders. Partial positive results have been obtained using various classes of drugs for dealing with aggression and impulsive behaviors, including lithium, beta-blockers, carbamazepine, valproate, antipsychotic drugs, and also SSRIs. Self-harm and suicidal behaviors seem to be partially but significantly improved by antidepressants and low doses of antipsychotics. Overall, the pharmacotherapy of personality disorder may lead in the future to the development of effective treatments, in complement to psychotherapy, for actually severe, chronic, and disabling disorder.
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