After much negotiation with the Food and Drug Administration (FDA), Eli
Lilly and Co. has recently updated the labeling information of its atypical
antipsychotic drug olanzapine (Zyprexa) to highlight its effect on glucose
The labeling for olanzapine had carried the class warnings for the risks of
diabetes mellitus and weight gain as mandated by the FDA since 2003
(Psychiatric News, October 17, 2003).
Clinical reports have accumulated in recent years to suggest that
olanzapine has a greater effect on weight gain and glucose metabolism than do
other atypical antipsychotics. In the package insert for olanzapine, dated
October 1, the warnings section has been expanded to include hyperglycemia,
hyperlipidemia, and weight gain. Data in adults and adolescents are presented
separately (olanzapine is not approved for use in patients under age 18).
Notably, the warnings acknowledge that "the association between atypical
antipsychotics and increases in glucose levels appears to fall on a continuum,
and olanzapine appears to have a greater association than some other atypical
antipsychotics." The warnings also contain wordings about"
significant, sometimes very high (>500 mg/dL) elevations of
triglyceride levels" and "modest mean increases in total
cholesterol" associated with olanzapine use.
The drug-label changes reflect pooled adverse-event data in Lilly's
clinical trials and reports in the Clinical Antipsychotic Trials of
Intervention Effectiveness (CATIE) and Comparison of Atypicals for
First-Episode Psychosis (CAFE) studies, according to the company's press
release on the labeling changes. Both studies involved long-term, head-to-head
comparisons of atypical antipsychotic drugs. The CATIE study was funded by the
National Institute of Mental Health, and the CAFE study was funded by
AstraZeneca, the maker of quetiapine (Seroquel).
APA has commissioned a work group to review all available evidence
concerning the metabolic risks of antipsychotic drugs. John Newcomer, M.D.,
who is a professor in the psychiatry, psychology, and medicine departments and
medical director of the Center for Clinical Studies at Washington University
School of Medicine in St. Louis and leads the APA effort, told Psychiatric
News that the report resulting from the review will present a
comprehensive overview of the background and available clinical evidence on
this medical issue. The paper will also provide clinical recommendations for
screening, monitoring, and reducing cardiovascular and metabolic risks in
patients treated with antipsychotic medications. The draft is expected to be
The FDA's efforts that led to Lilly's olanzapine labeling change are an
acknowledgement of the evidence, including high-quality data from the
NIMH-funded CATIE study, that has consistently shown the differential risks of
weight gain, altered triglyceride levels, and potential hyperglycemia across
different antipsychotics, said Newcomer.
He strongly urged psychiatrists, primary care providers, and health care
systems to screen and monitor schizophrenia patients more actively for weight,
body mass index, lipid profiles, glucose levels, blood pressure, and key
indicators of cardiometabolic risks.
"Unfortunately, psychiatrists cannot assume that an internist or
primary care provider is taking care of [cardiovascular assessments and
treatments], often because patients do not see any physician besides their
psychiatrist. Psychiatrists should participate in the screening and monitoring
of metabolic risk at the start of and during antipsychotic treatment and make
appropriate referrals to primary or specialty care providers to address
identified risk factors and, importantly, follow up on these referrals,"
Earlier this year Lilly announced billions of dollars in legal settlements
with patients who filed suits alleging that they were harmed by the drug. The
plaintiffs also alleged that Lilly withheld or downplayed information
regarding significant adverse effects associated with olanzapine, though Lilly
denies any such wrongdoing, according to reports in the January 5 New York
Times and February 2 Psychiatric News.
The updated labeling information for olanzapine is posted at<pi.lilly.com/us/zyprexa-pi.pdf>.▪