Evidence-Based Reviews

New uses for atypicals in pediatric patients: How to offer the benefits while minimizing side effects

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References

Olanzapine. Recent interest in olanzapine’s thymoleptic propertities has contributed to its clinical use in bipolar disorder, specifically in psychotic mania. Olanzapine has also been studied as long-term maintenance therapy in bipolar disorder. In a 47-week study, adult patients receiving olanzapine improved significantly more than those receiving valproate (47% vs. 34% by the Young Mania Rating Scale) after 3 weeks. Both medications were effective throughout the long-term, randomized, double-blind study.29

Two case series and one open trial have examined olanzapine as primary or adjunctive treatment for children and adolescents with bipolar disorder. In the open study, Frazier and colleagues gave olanzapine, 2.5 to 20 mg/d, to 23 children ages 5 to 14.30 After 8 weeks, the response rate was 61% (defined as 30% or greater improvement on the Young Mania Rating Scale). Weight gain was the predominant side effect (mean increase 5 kg).

Chang and colleagues demonstrated “marked improvement” in CGI scores when using olanzapine as adjunctive therapy for three youths with bipolar disorder.31 Similar findings were reported when treating seven youths with acute mania.32 Olanzapine’s broad affinity for dopaminergic and serotonergic receptors may explain these positive outcomes.

Other atypicals. No studies have been published on the use of quetiapine, ziprasidone, or aripiprazole in childhood mood disorders.

Psychotic depression

Psychosis can complicate depression in adults and adolescents. In a small study of adolescents with psychotic depression, Gellar et al demonstrated conventional neuroleptics’ benefit in combination with antidepressants.33 We have no data, however, on use of atypicals in childhood depression, and published accounts of depression in bipolar patients treated with atypicals are of some concern.

In one study,34 four of six patients with bipolar disorder developed dysphoric mood within 3 months of starting risperidone. Two met the criteria for major depression and required antidepressant therapy. This finding was somewhat surprising, given risperidone’s antidepressant benefit in some adults, most likely due to its 5-HT2 antagonistic effect. Frazier and colleagues similiarly noted that one patient discontinued treatment during an open-label trial examining the benefit of olanzapine in juvenile bipolar disorder.30

These findings in the adolescent bipolar population should not be ignored when you consider treating a primary depressive disorder with psychosis. Antipsychotics certainly can be useful for treating psychotic depression, especially acutely for stabilization and preventing harm to self. Atypical antipsychotics have consistently been proven to have less adverse side effects than typical antipsychotics and thus would be preferred in children and adolescents. Research is needed to examine possible worsening of dysphoria.

Related resources

  • Hermann RC, Yang D, Ettner SL, et al. Prescription of antipsychotic drugs by office-based physicians in the United States, 1989-1997. Psychiatric Services 2002;53:425-30.
  • Stigler KA, Potenza MN, McDougle CJ. Tolerability profile of atypical antipsychotics in children and adolescents (review). Paediatric Drugs 2001;3(12):927-94
  • American Academy of Child and Adolescent Psychiatry http://www.aacap.org
Drug brand names
  • Clozapine • Clozaril
  • Olanzapine • Zyprexa
  • Quetiapine • Seroquel
  • Risperidone • Risperdal
  • Ziprasidone • Geodon
  • Aripiprazole (investigational)
Disclosure

Dr. Londino reports that she serves as a consultant to Eli Lilly and Co.

Ms. Wiggins reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Buckley reports that he receives grant support from and serves as a consultant and speaker for AstraZeneca Pharmaceuticals, Eli Lilly and Co., Janssen Pharmaceutica, and Novartis Pharmaceuticals Corp.

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