January 2008

Treating Behavioral Problems in Dementia
No drug is clearly efficacious for behavioral problems in dementia, and all are associated with significant risks.

Prolactin Elevation and Antipsychotics
Risperidone (Risperdal) seems to increase prolactin more than conventional and other second-generation antipsychotics; adjunctive aripiprazole (Abilify) may lower antipsychotic-induced hyperprolactinemia.

In Brief
Atomoxetine Effective for ADHD in Preschool Children; Excessive Body Weight Increases Risk of Dementia

Treating Adolescent Mania
Olanzapine (Zyprexa) effectively treats adolescent bipolar disorder but appears to cause harmful medical consequences in young patients.

Isotretinoin and Depression
Depression is a possible side effect of treatment with isotretinoin (Accutane and others).

Treating Adolescent Mania

January 2008

A carefully designed study demonstrated the good, the bad, and the uncertain in the treatment of adolescents with bipolar mania. Tohen and others enrolled 161 patients, 13 to 17 years old, with an acute manic or mixed episode in a 3-week, double-blind, randomized trial.1 Subjects received either olanzapine (Zyprexa), 2.5 to 20 mg/day, or placebo.

Patients who took olanzapine did substantially better: for example, 44.8% achieved "response" versus only 18.5% of those given placebo (P < .05). But not unexpectedly, the percentage of subjects whose body weight increased by at least 7% was substantially higher with olanzapine: 41.9% versus 1.0%. Similar worsening was seen in a number of laboratory indices: prolactin, fasting glucose, fasting total cholesterol, uric acid, and two hepatic enzymes.

In an accompanying editorial, McClellan points out that pediatric bipolar disorder remains the focus of a hot debate, with both the definition and diagnosis controversial.2 He also highlights the inadequacy of data on treating adolescents with bipolar disorder, referring to the report by Dr Tohen's group as the first adequately powered controlled trial of a second-generation antipsychotic in this population. Adolescents in the Tohen study gained more weight than typically seen in adult patients, increasing an average of 3.6 kg (8 lb) in only 3 weeks. While this study demonstrates olanzapine's efficacy, the weight gain and adverse metabolic indices suggest that longer term use could have harmful medical consequences—perhaps worse in young patients than in adults. The editorial questions the risk-benefit ratio of olanzapine as a first-line treatment in juveniles.

Treating bipolar disorder in adult patients is no easy task. As with so many conditions, data are sparse in young populations, but their need for treatment can be substantial. The clinician is left to face the dilemma, which should be done, if possible, in close collaboration with parents.

1Tohen M, Kryzhanovskaya L, Carlson G, DelBello M, Wozniak J, Kowatch R, Wagner K, Findling R, Lin D, Robertson-Plouch C: Olanzapine versus placebo in the treatment of adolescents with bipolar mania. Am J Psychiatry 2007;164:1547-1556.

2McClellan JM: Olanzapine and pediatric bipolar disorder: Evidence for efficacy and safety concerns. Am J Psychiatry 2007;164:1462-1464.