FDA Advises Caution in Olanzapine Use in Teens

The approval of olanzapine for two pediatric indications—the treatment of schizophrenia and of manic or mixed episodes associated with bipolar I disorder in adolescents aged 13 to 17 years—comes with a precaution.

The Food and Drug Administration is advising clinicians to consider the increased potential for weight gain associated with the antipsychotic in adolescents, compared with adults.

Olanzapine (Zyprexa) was approved in December for the two indications based on two short-term studies—one, a 6-week trial of 107 adolescents with schizophrenia; the other, a 3-week study of 161 adolescent inpatients and outpatients with manic or mixed episodesassociated with bipolar I disorder.

The indications section of the revised label for both bipolar I disorder and schizophrenia includes the following statement: “When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and hyperlipidemia. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases, this may lead them to consider prescribing other drugs first in adolescents.”

In clinical trials, sedation and greater increases in prolactin and hepatic transaminase levels were higher in adolescents, compared with those in adults.

The label also includes a statement that says that the diagnosis of pediatric schizophrenia and bipolar I disorder “can be challenging” and recommends that medication therapy for these disorders “be initiated only after a thorough diagnostic evaluation has been performed and careful consideration given to the risks associated with medication treatment.” It also says that medication treatment for these disorders should “be part of a total treatment program that often includes psychological, educational, and social interventions.”

The statements reflect comments made at a meeting of the agency's Psycho-pharmacologic Drugs Advisory Committee in June, when the panel reviewed short-term data on olanzapine for these two indications, on quetiapine (Seroquel) for treating schizophrenia in adolescents aged 13–17 years and bipolar mania in children and adolescents aged 10–17, and on ziprasidone (Geodon) for manic or mixed episodes associated with bipolar disorder in children and adolescents aged 10–17.

For olanzapine, the panel voted 11 to 5, with 2 abstentions, that the drug had been shown to be an effective treatment for schizophrenia in patients aged 13–17. Ten voted that it had been shown to be “acceptably safe” for this indication.

However, four panelists voted no on the safety question, and four abstained, citing concerns that included the well-known metabolic effects of olanzapine.

The panel also voted 17 to 0, with 1 abstention, that the drug had been shown to be effective for treating bipolar mania for the same age group and 11 to 4, with 3 abstentions, that it had been shown to be acceptably safe in this age group for this indication. Those voting in the affirmative on safety and efficacy for both indications said they considered the drug as a second-line treatment because of its metabolic effects.

At the June meeting, Dr. Thomas Laughren, head of the FDA's Division of Psychiatry Products, said the olanzapine label would advise clinicians to consider other drugs before this one, because of concerns about its metabolic effects.

At a December meeting of the Pediatric Advisory Committee, Dr. Laughren noted that as a result of a comprehensive review of the weight gain associated with the atypical anti-psychotics currently underway at the agency, information about the metabolic effects of the atypical antipsychotics probably would be moved to the boxed warning of the labels.

The panel unanimously agreed at that meeting that the current labeling does not adequately address the risk of weight gain associated with these agents.