Olanzapine, a newer generation "atypical" antipsychotic, is the first drug in its class to be approved by the U.S. Food and Drug Administration (FDA) for long-term (longer than six weeks) schizophrenia therapy and maintenance of treatment response.

The new indication is the third for the powerful antipsychotic introduced by Eli Lilly and Company in 1996 under the trade name Zyprexa. Earlier this year the FDA approved the drug for the short-term treatment of acute manic episodes associated with bipolar disorder.

Olanzapine’s efficacy and long-term safety were demonstrated in studies submitted to the FDA by Lilly comparing it with placebo in the maintenance of treatment response in schizophrenia. According to Lilly’s submission to the FDA, the response to olanzapine was so strong that Lilly terminated the studies early to limit unnecessary patient exposure to the placebo.

Placebo-treated patients were nearly 10 times more likely to relapse over a six-month period compared with those taking olanzapine. Cumulative relapse rates over the six months were 6 percent for olanzapine and 56 percent for placebo.

The Lilly studies followed 326 clinically stable outpatients who were diagnosed with schizophrenia or schizoaffective disorder and who exhibited few or no symptoms for at least six weeks prior to the start of the study. Study subjects received oral olanzapine for six weeks, then were observed to document stability on olanzapine for an additional eight weeks. The group was then randomly assigned to either continuing olanzapine therapy or placebo.

Patients receiving olanzapine were found to be significantly less likely than those on placebo to discontinue treatment as a result of a lack of efficacy. Additionally, patients receiving olanzapine were less likely to report an apparent adverse drug event than those receiving placebo. Olanzapine-treated patients were also found to improve on all quality-of-life measures, while the patients receiving placebo worsened. Patients receiving olanzapine received between 10 mg and 20 mg a day.

Patients taking olanzapine in this latest study exhibited treatment-emergent side effects similar to those seen in the original clinical trials and in postmarketing surveillance. The most common adverse effect associated with olanzapine was somnolence. Also commonly reported were dizziness, weight gain, constipation, restlessness, and postural hypotension.

Although modest elevations of prolactin were also seen, mean changes from baseline to endpoint were not statistically significant between olanzapine and placebo. A small number of patients also exhibited a mild elevation of hepatic transaminase; however, none exhibited symptoms. No cases of jaundice or drug-induced hepatitis were reported.