Eli Lilly and Company pleaded guilty on January 30 to one misdemeanor violation of misbranding Zyprexa (olanzapine) by promoting it for dementia. However, a question raised by bloggers and others remains: did the drug benefit the elderly despite the fact it was not approved by the FDA for such purposes?
“Off-label promotion is an important legal issue,” said geriatric psychiatrist David Sultzer, MD, professor of psychiatry and biobehavioral sciences at the University of California, Los Angeles. “But off-label prescribing isn’t equivalent to unethical or inappropriate use.”
“Off-label prescribing of drugs is widespread, dependent on several factors, and not necessarily a bad thing,” he noted. “However, clinicians need to be making wise decisions with off-label use because the drugs aren’t approved for that use and the evidence base may be limited.”
In mid-January, the Department of Justice filed a criminal information against Lilly. (A criminal information is an accusation. A defendant is presumed innocent unless and until proved guilty.) It alleged that the company, among other actions, engaged in off-label marketing by promoting Zyprexa for elderly patients with dementia and with sleep disorders; that Lilly knew significant weight gain was an adverse effect of the drug but touted it as a therapeutic benefit; that Lilly instructed its sales force to recommend Zyprexa for adult patients with behavioral symptoms, such as agitation, aggression, hostility, and mood and sleep disturbances; and that Lilly’s management created marketing materials that promoted off-label uses.
Angela Sekston, executive director of external communications and corporate social responsibility for Lilly, told Psychiatric Times that the “company deeply regrets” its conduct related to promoting the drug for Alzheimer disease/dementia between September 1999 and March 31, 2001, but it does not agree with some of the broader claims and “acknowledges no wrongdoing here in the court records.”
After Lilly pleaded guilty to the misdemeanor count, District Court Judge Robert Kelly imposed sentence, and ordered the Indiana-based company to pay $515 million—one of the largest individual corporate criminal fines in history—and to forfeit an additional $100 million in assets.
Lilly also signed a civil settlement to resolve claims that by marketing Zyprexa for unapproved uses, it caused false claims for payment to be submitted to federal insurance programs, such as Medicaid, TRICARE, and the Federal Employee Health Benefits Program. None of these programs provided coverage for such off-label uses, according to a Department of Justice statement.
Under the settlement, Lilly pays an additional $800 million to the federal government and the states to resolve civil allegations originally brought in 4 separate lawsuits under the qui tam provision of the federal False Claims Act. The federal share of the settlement amount is $438,171,543, of which $78,870,877 will go to whistleblowers—former sales representatives who identified Lilly’s off-label marketing practices. The state Medicaid programs and the District of Columbia will share up to $361,828,456 of the civil settlement, depending on the number of states that participate. For example, California is expected to recover $54 million for its Medi-Cal program. Florida is expected to get $35 million.
1. Jeste DV, Blazer D, Casey D, et al. ACNP White Paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology. 2008;33:957-970.
2. Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med. 2006;355: 1525-1538.
3. Sultzer DL, Davis SM, Tariot PN, et al. Clinical symptom responses to atypical antipsychotic medications in Alzheimer’s disease: phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry. 2008; 165:844-854.
4. Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009;360:225-235.
5. Schneeweiss S, Avorn J. Antipsychotic agents and sudden cardiac death—how should we manage the risk? N Engl J Med. 2009;360:294-296.