ADELPHI, MD. — The majority of a Food and Drug Administration advisory panel agreed that the data on the atypical antipsychotic olanzapine indicated that it was effective and had an acceptable safety profile for treating two pediatric indications: schizophrenia and bipolar mania in patients aged 13-17 years.
At a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, the panel voted 11-5, with 2 abstentions, that olanzapine had been shown to be effective as a treatment for schizophrenia in this age group, with the majority—10 panelists—voting that it had been shown to be “acceptably safe” for this indication. However, four of the 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 17-0, with 1 abstention, that the drug had been shown to be effective for treating bipolar mania, and voted 11-4, with 3 abstentions, that it had been shown to be acceptably safe in this age group for this indication.
Those voting positively on safety and efficacy for both indications said that they considered the drug as a second-line treatment, because of its metabolic effects. If approved, the label would advise clinicians to consider drugs before this one, because of concerns over its metabolic effects, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, said at the meeting.
Olanzapine is marketed as Zyprexa by Eli Lilly and Co., and is approved for treating schizophrenia and bipolar disorder in adults.
Eli Lilly presented the results of a short-term study of 107 patients aged 13-17 with schizophrenia, comparing 2.5 mg to 20 mg per day of olanzapine to placebo over 4 weeks. The primary efficacy end point—the changes in the Brief Psychiatric Rating Scale-for Children (BPRS-C) total score from baseline to end point—found a significantly greater effect among those on olanzapine, with an effect size comparable to that seen in adult studies, according to the company.
In another study of 161 patients aged 13-17 years with bipolar disorder who were in an acute manic or mixed episode, those who received 2.5 mg to 20 mg per day of olanzapine had reductions in the Young Mania Rating Scale (YMRS) total score (the primary efficacy end point) that were significantly greater than the reductions seen among those on placebo, after 3 weeks of treatment.
In the two studies combined, sedation-related events were the most common adverse events associated with treatment (44% among those on olanzapine, compared with 9% of those on placebo), followed by increases in weight (almost 30%, compared with almost 6%, respectively), and increased appetite (24%, compared with 5.6%, respectively). Among those on olanzapine, 8% had elevated liver enzymes, compared with 1% of those on placebo.
The differences in these adverse events were all significantly greater among the patients who were taking olanzapine.
In addition to weight gain, increases in fasting glucose, fasting total cholesterol, fasting triglycerides, and prolactin levels have been documented in adolescents treated with olanzapine for 12 weeks or less, and for longer durations, according to Eli Lilly.
The increased risks of weight gain, hyperlipidemia, hyperglycemia, and hyperprolactinemia associated with olanzapine use in adolescents are included in the drug's label, even though the drug has not been approved for this age group.