October 2009

Divalproex for Mania in Children and Adolescents: A Negative Study
The first double-blind study of divalproex (Depakote) in pediatric patients with bipolar disorder found no greater efficacy than placebo.

Chamomile Calms
A double-blind study suggests efficacy for chamomile as an alternative treatment for anxiety.

Quetiapine for GAD and MDD
In a variety of studies, quetiapine (Seroquel) was found to be effective in treating generalized anxiety and major depressive disorders.

In Brief
Valproate Does Not Improve Agitation in Patients with Dementia; Three More Atypical Antipsychotics May Be Approved for Pediatric Patients

Child and Adolescent Topics
Keep an eye out for BTP's new icon denoting articles about children and adolescents.

In Brief

October 2009

Although preparations of valproate (Depakote and others) have been used for at least the past decade to treat agitation in elderly patients with dementia, there is little evidence that valproate provides benefit for this indication (BTP 2008;31:35-36). A 2004 systematic review of three randomized, placebo-controlled trials of valproate in patients with dementia found that low doses (480 mg/day) were ineffective in improving agitation, and higher doses (1000 mg/day) increased the frequency of adverse effects to an unacceptable level. This review was updated in 2008 with two new studies and a meta-analysis of pooled results (Lonergan E, Luxenberg J. Cochrane Database Syst Rev 2009(3):CD003945). Again, investigators found that valproate preparations failed to improve agitation among demented patients compared with control subjects and were associated with a prohibitive rate of adverse events, including falls, infection, gastrointestinal disorders, and decreased platelet counts. The authors conclude that current evidence does not support the use of this medication to control agitation in people with dementia.

Two second-generation antipsychotic drugs—risperidone (Risperdal and others) and aripiprazole (Abilify)—are currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of children and adolescents with bipolar disorder or schizophrenia. In June, an FDA advisory panel recommended the approval of three others for this indication: quetiapine (Seroquel), ziprasidone (Geodon), and olanzapine (Zyprexa) (Kuehn BM, JAMA 2009;302:833-834). However, the panel was divided over the safety of these medications for this age group. Adverse effects associated with these atypical antipsychotics, such as somnolence, weight gain, increases in blood lipids and glucose, and certain movement disorders, could affect growth and development. In particular, there were concerns about the cardiovascular risks of ziprasidone, which can increase the QT interval and lead to sudden death, and the metabolic effects of olanzapine, which has been associated with greater weight gain than the other two agents. A further concern was that since some clinicians use looser criteria to diagnose bipolar disorder in children than they do in adults, some pediatric patients who do not actually have bipolar disorder may be unnecessarily exposed to these medications. The panel recommended and the FDA agreed that bipolar disorder should be narrowly defined based on DSM-IV criteria on the drugs' labels. A final decision about whether quetiapine, ziprasidone, and olanzapine will be labeled for the treatment of bipolar disorder and schizophrenia in pediatric patients will be made by the FDA, but the agency generally follows the advisory committee's advice.

Heather S. Hopkins