Off-Label Drug Use Is Common and Hurts Nursing Home Residents
The three-year old, and still ongoing, investigation and criminal prosecution of former staff members of a California skilled nursing facility for improper use of antipsychotic drugs on residents raises issues that go far beyond the gruesome facts of the case; issues that remain current today.
This Alert discusses that case, research and Federal Drug Administration (FDA) action related to the issues raised in the case, and advocacy steps available to people seeking to help nursing home residents who are victims of such abuses.
In January 2007, a nursing home ombudsman reported to the California Department of Public Health that a resident at a Kern Valley skilled nursing facility had been held down and forcibly injected with a form of psychotropic medication from the group of drugs known as atypical antipsychotic drugs. According to the state Attorney General, the Department
[s]ent an investigative team with a doctor, a nurse, and a doctor of pharmacology [who] determined that 22 patients, including some who were suffering from Alzheimer’s at the skilled nursing facility, were being given high doses of psychotropic medication not for therapeutic reasons, but to simply control and quiet them for the convenience of the staff.
The health department cited the nursing facility with immediate jeopardy, the highest level of deficiency in the federal regulatory system, for administering psychotropic medications as chemical restraints to 22 residents. It referred the case to the State Attorney General.
Following a year-long investigation, the State charged the former Director of Nursing (DoN), pharmacist, and medical director in a 10-count felony complaint, with elder abuse resulting in death. The DoN and pharmacist were also charged with assault with a deadly weapon for allegedly forcibly injecting residents with drugs. The State alleged that during her five-month tenure, the DoN ordered psychotropic medications for residents for “glaring, responding to her in a disrespectful manner, or refusing to eat dinner in the dining room.” Three residents were alleged to have died and other residents were alleged to have “suffered weight loss, body tremors, slurred speech, sat in geri chairs all day with glazed eyes.” The DoN had been fired from a different nursing facility in 1999 after the facility was cited with a deficiency for over-medicating residents with psychotropic drugs.
To date, the pharmacist has pleaded guilty to one felony count of conspiracy to commit an act injurious to public health; she is cooperating with the State. The facility administrator was added as a defendant.
Although this ongoing criminal prosecution represents an extreme example, the misuse of antipsychotic medications in the treatment (or control) of nursing home residents is pervasive. In the fourth quarter of 2009, the federal government reports that 26.1% of the nation’s 1,359,787 nursing home residents – 354,904 people – received antipsychotic drugs. Studies discussed below also report that 25-30% of nursing home residents nationwide are given these drugs, frequently for reasons not approved by the FDA. Many residents are dying. In February 2007, David Graham, M.D., MPH, Associate Director, Science and Medicine, FDA Office of Surveillance and Epidemiology, testified in the House of Representatives that, by his estimate, “15,000 elderly people in nursing homes [are] dying each year from the off-label [i.e., not FDA-approved] use of antipsychotic medications for an indication that FDA knows the drug doesn’t work.”
The Use of Atypical Antipsychotic Drugs for Nursing Home Residents
Atypical antipsychotic drugs (including Seroquel, Risperdal, and Zyprexa) were developed in the 1990s and were believed to have fewer side effects than older, conventional, antipsychotic drugs such as Haldol. Although approved by the FDA for people with psychoses such as bipolar disorder and schizophrenia, atypical antipsychotic drugs have been used off-label for large numbers of nursing home residents who have dementia, but no psychoses. Under federal law, physicians are allowed to prescribe drugs for uses other than those specifically approved by the FDA, but drug companies may not market drugs for off-label uses.
In April 2005, the FDA issued “black box” warnings against prescribing atypical antipsychotic drugs for patients with dementia, cautioning that the drugs increased dementia patients’ mortality. In June 2008, the FDA extended its warning to all categories of antipsychotic drugs, conventional as well as atypical, and directly and unequivocally advised health care professionals, “Antipsychotics are not indicated for the treatment of dementia-related psychosis.”
Research Literature and the Popular Press Identify the Extensive Off-Label Use of Atypical Antipsychotic Medications for Nursing Home Residents
A retrospective analysis of the use of anti-psychotic drugs by Medicare beneficiaries in nursing homes in 2000-2001 found the highest rate of antipsychotic drug use in more than a decade. The analysis reported that 27.6% of residents received at least one prescription for antipsychotic drugs and that, of those, more than half (58.2%) “took doses exceeding maximum levels, received duplicative therapy, or had inappropriate indications according to guideline requirements.” The atypical antipsychotic drugs were inappropriately used for residents with depression, dementia, and nonaggressive behavior problems, such as restlessness, unsociability, uncooperativeness, and indifference to surroundings. Resident outcomes did not improve with use of the atypical antipsychotics. The most common atypical antipsychotic prescribed in 2000-2001 was risperidone (trade name, Risperdal).
Using data from the 2004 National Nursing Home Survey, a later study found that 23.5% of residents received at least one atypical antipsychotic drug, that 86.3% of the drug use was off-label, and that 43% of the use “was without strong scientific support.”
Although the FDA’s black box warning led to some decreases in the use of atypical antipsychotics for elderly patients with dementia, a recently-released study of nursing home residents who were admitted in 2006 – after the first black box warning was issued – found that more than 29% of newly-admitted residents received at least one antipsychotic medication in 2006 and that 32% of those residents “had no identified clinical indication for this therapy.”
The popular press has also reported the overmedication of nursing home residents with antipsychotic drugs. Reviewing more than 40,000 federal and state inspection reports for Illinois’ 742 nursing facilities, the Chicago Tribune, in an article in 2009, identified 1200 violations involving psychotropic medications and affecting 1900 residents, since 2001. The Chicago Tribune identified 12 resident deaths and dozens of incidents where residents broke bones after falling while they were medicated. The reasons for the medication: one resident “was ‘yelling out’ and ‘easily annoyed;'” another resident “was teasing another resident and generally being ‘nasty.'” Earlier this month, the Boston Globe reported that nearly 28% of all Massachusetts nursing home residents were given antipsychotic drugs in 2009 and that 22% of them (2483 residents) did not have a medical condition supporting use of the drug.
Litigation against Drug Companies
The extensive use of atypical antipsychotic drugs for nursing home residents may in part reflect drug companies’ marketing of such off-label uses for residents, as reflected in recent litigation by the United States against a drug company and the nation’s largest nursing home pharmacy.
In January 2009, Eli Lilly & Company pleaded guilty to the misdemeanor of introducing misbranded drugs into interstate commerce. Between September 1999 and November 2003, its long-term care sales force, as trained by the company, promoted Zyprexa for the treatment of dementia, depression, anxiety, and sleep problems in nursing home residents, read more at the MyEtizolam website. Admitting its off-label marketing, the company agreed to pay the United States a criminal fine of $615 million. At the same time, the company entered a separate civil settlement under the federal False Claims Act, admitting that it “caused invalid claims for payment for Zyprexa to be submitted to various government programs.” Eli Lilly agreed to pay a civil fine of $835 million to the United States and states. Between 2000 and 2008, Eli Lilly received $36 billion in revenues for Zyprexa, “more than 25 times as much as the total penalties Lilly paid in January.”
In November 2009, Omnicare, the nation’s largest nursing home pharmacy, agreed to pay $98 million and the drug manufacturer IVAX Pharmaceuticals agreed to pay $14 million to the United States to resolve allegations involving kickbacks paid to Omnicare by Johnson & Johnson in exchange for Omnicare’s consultant pharmacists’ recommending the antipsychotic drug Risperdal for nursing home residents. The United States has also joined two separate False Claims Act lawsuits – one against two nursing home chains, Mariner Health Care and SavaSenior Care, and their principals, alleging that Omnicare paid the chains $50 million “in exchange for the right to continue providing pharmacy services to the nursing homes,” and a second, against Johnson & Johnson and two of its subsidiaries, alleging that they paid kickbacks to Omnicare “to induce Omnicare and its pharmacists to recommend J&J drugs,” including Risperdal.
Various actions are available to advocates to address the inappropriate medication of residents with antipsychotic drugs.
Nursing Home Reform Law
Regulations implementing the federal Nursing Home Reform Law explicitly limit the use of antipsychotic drugs. 42 C.F.R. §483.25(l)(2) provides:
(2) Antipsychotic Drugs. Based on a comprehensive assessment of a resident, the facility must ensure that—
(i) Residents who have not used antipsychotic drugs are not given these drugs unless antipsychotic drug therapy is necessary to treat a specific condition as diagnosed and documented in the clinical record; and
(ii) Residents who use antipsychotic drugs receive gradual dose reductions, and behavioral interventions, unless clinically contraindicated, in an effort to discontinue these drugs.
Guidance issued by the Centers for Medicare & Medicaid Services encourages facilities to use non-pharmacological alternatives, identifies situations where antipsychotic medications are not indicated, and provides an investigative protocol for unnecessary drugs, including antipsychotic drugs.
In 2005, the State of Minnesota responded to the FDA’s black box warning and CMS’s new guidance on unnecessary drugs by training its surveyors on antipsychotic drug use. The state’s stepped-up enforcement of the federal regulations led to a decline in nursing facilities’ use of antipsychotic drugs with residents who did not have a diagnosis of psychosis.
State legislation may strengthen informed consent rules and practice. A bill pending in the state legislatures in Wisconsin would require that a resident or, if the resident is incapacitated, a person acting on the resident’s behalf, give informed written consent before any antipsychotic drug with a black box warning is given to the resident. Similar legislation introduced in Massachusetts would require informed consent from “the resident, the resident’s health care proxy, and a court appointed Rogers guardian” before any psychotropic medication is prescribed. Similar types of legislation addressing nursing home residents and antipsychotic drugs are under consideration in other states.
California Advocates for Nursing Home Reform (CANHR), a statewide resident advocacy organization, has developed a consumer brochure to explain psychoactive drugs, including antipsychotic drugs taken by a quarter of California nursing home residents, and how families can advocate to stop their inappropriate use.
Although the research articles discussed in this Alert generally reflect practices from several years ago, current data indicate that antipsychotic drugs are still commonly taken by nursing home residents. Medical evidence demonstrating the harm of antipsychotic drugs for residents with dementia and federal regulations requiring that residents be free from unnecessary drugs do not appear to have led to significant reductions in antipsychotic drug use in nursing homes.
The Center is interested in hearing from advocates on this issue. Contact attorney Toby S. Edelman (firstname.lastname@example.org) in the Center for Medicare Advocacy’s Washington, DC office at (202) 293-5760.
 Office of the Attorney General, “Brown Announces Arrests of Nursing Home Employees Who Drugged Patients for Staff’s Convenience” (News Release, Feb. 18, 2009), http://ag.ca.gov/newsalerts/release.php?id=1682.
 People of the State of California v. Gwen D. Hughes, Debbi C. Hayes, Hoshang M. Pormir, M.D., (Calif. Super. Ct., Kern Co. Feb. 2009) (Felony Complaint). Criminal complaint, http://ag.ca.gov/cms_attachments/press/pdfs/n1682_2-4-09_-_
felony_complaint.pdf; declaration in support of criminal complaint, http://ag.ca.gov/cms_attachments/press/pdfs/n1682_2-4-09_-_declaration_in_support_of_felony_complaint.pdf; “Reports detail fatal druggings at nursing facility,” The Bakersfield Californian (Feb. 19, 2009), http://www.bakersfield.com/102/story/694429.html; “3 arrested in nursing home deaths in Lake Isabella,” Los Angeles Times (Feb.20, 2009), http://www.latimes.com/news/local/la-me-nursing-home-deaths20-2009feb20,0,3095223.story; “How did accused nurse keep getting hired?,” The Bakersfield Californian (Feb. 20, 2009).
 Centers for Medicare & Medicaid Services, MDS Active Resident Information Report: Fourth Quarter 2009, O4a: Medications – Days Received the Following Medication – Antipsychotic,
 Subcommittee on Oversight and Investigations, House Committee on Energy and Commerce, “The Adequacy of FDA to Assure the Safety of the Nation’s Drug Supply,” 110th Cong., First Sess. (March 13, 2007), Serial No. 110-5, page 66, http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_house_hearings&docid=f:35502.pdf.
 FDA, “Public Health Advisory: Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances” (April 5, 2005), http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm053171.htm.
 FDA, “Information for Healthcare Professionals: Conventional Antipsychotics,” FDA Alert (June 16, 2008), http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124830.htm.
 Becky A. Briesacher, Rhona Limcangco, Linda Simoni-Wastila, Jalpa A. Doshi, Suzi R. Levens, Dennis G. Shea, Bruce Stuart, “The Quality of Antipsychotic Drug Prescribing in Nursing Homes,” Arch Intern Med., Vol. 165 (June 13, 2005), http://archinte.ama-assn.org/cgi/reprint/165/11/1280?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Briesacher&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT.
 Pravin Kamble, Jeff Sherer, Hua Chen, Rajender Aparasu, “Off-Label Use of Second-Generation Antipsychotic Agents Among Elderly Nursing Home Residents,” Psychiatric Services, Vol. 61, No. 2, p. 130 (Feb. 2010). Abstract available at http://ps.psychiatryonline.org/cgi/content/abstract/61/2/130?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Kamble&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=
HWCIT. Shekelle P, “Effectiveness of Off-Label Use of Atypical Antipsychotics: Comparative Effectiveness Review No. 6 (Jan. 2007), AHRQ Publication No. 07-EHC003-EF, http://www.effectivehealthcare.ahrq.gov/ehc/products/5/63/Atypical_
Antipsychotics_Final_Report.pdf; eight-page Executive Summary at http://www.effectivehealthcare.ahrq.gov/ehc/products/5/64/Atypical_Executive_Summary.pdf. See also Stephen Crystal, Mark Olfson, Cecilia Huang, Harold Pincus, Tobias Gerhard, “Broadened Use Of Atypical Antipsychotics: Safety, Effectiveness, And Policy Challenges,” Health Affairs, Vol. 28, No. 5 (July 21, 2009).
 E. Ray Dorsey, Atonu Rabbani, Sarah A. Gallagher, Rena M. Conti, G. Caleb Alexander, “Impact of FDA Black Box Advisory on Antipsychotic Medication Use,” Arch Internal Medicine, Vol. 170, No. 1 (Jan. 11, 2010), Abstract, http://archinte.ama-assn.org/cgi/content/abstract/170/1/96.
 Yong Chen, Becky A. Briesacher, Terry S. Field, Jennifer Tjia, Denys T. Lau, Jerry H. Gurwitz, “Unexplained Variation Across US Nursing Homes in Antipsychotic Prescribing Rates,” Arch Internal Medicine, Vol. 170, No. 1 (Jan. 11, 2010), http://archinte.ama-assn.org/cgi/content/abstract/170/1/89. Residents who were admitted to facilities that had the highest rates of antipsychotic drug use “were 1.37 times more likely to receive antipsychotics relative to those entering the lowest prescribing rate [nursing homes].”
 Sam Roe, “Compromised Care: Psychotropic drugs given to nursing home patients without cause. Many Illinois residents get medications they don’t need or want. The result? A threat to the lives of the elderly,” Chicago Tribune (Oct. 27, 2009).
 Kay Lazar, “Nursing home drug use puts many at risk; Antipsychotics given to some with dementia,” Boston Globe (March 8, 2010), http://www.boston.com/news/local/massachusetts/articles/2010/03/08/antipsychotic_drug_use_for_dementia_
 U.S. Department of Justice, “Pharmaceutical Company Eli Lilly to Pay Record $1.45 Billion for Off-Label Drug Marketing; Criminal Penalty is Largest Individual Corporate Criminal Fine” (News Release, Jan. 15, 2009). Criminal Information, http://www.usdoj.gov/usao/pae/News/Pr/2009/jan/lillyinfo.pdf; guilty plea agreement, at http://www.usdoj.gov/usao/pae/News/Pr/2009/jan/lillyguiltypleaagreement.pdf; Department of Justice press release, http://www.usdoj.gov/usao/pae/News/Pr/2009/jan/lillyrelease.pdf; Government’s Memorandum for Entry of Plea and Sentencing, http://www.usdoj.gov/usao/pae/News/Pr/2009/jan/lillygovtmementrypleasent.pdf; Corporate Integrity Agreement, http://www.usdoj.gov/usao/pae/News/Pr/2009/jan/lillycorpintegagreement.pdf; and the Settlement Agreement, http://www.usdoj.gov/usao/pae/News/Pr/2009/jan/lillysignedsettlementagreement.pdf.
 David Evans, “When Profit Outweighs Penalties,” Washington Post (March 21, 2010), http://www.washingtonpost.com/wp-dyn/content/article/2010/03/19/AR2010031905578.html?sub=AR.
 U.S. Department of Justice, “Nation’s Largest Nursing Home Pharmacy and Drug Manufacturer to Pay $112 Million to Settle False Claims Act Cases; U.S. Also Files Complaint Against Two Atlanta-Based Nursing Home Chains and Their Principals” (News Release, Nov. 3, 2009). Complaint of the United States ,
http://www.phillipsandcohen.com/CM/NewsSettlements/United%20States%20v%20%20Omnicare%20Mariner%20et%20al%20%20complaint.pdf; Department of Justice News Release, http://www.justice.gov/opa/pr/2009/November/09-civ-1186.html; United States Attorney for Massachusetts News Release, http://www.justice.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Nov2009/OmnicarePR.html.
 Complaint and 55 Exhibits, http://www.justice.gov/usao/ma/J&J.html; Department of Justice News Release, http://www.justice.gov/opa/pr/2010/January/10-civ-042.html; U.S. Attorney Press Release, http://www.justice.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Jan2010/JohnsonandJohnsonPR.html.
 State Operations Manual, Appendix PP, http://cms.hhs.gov/manuals/Downloads/som107ap_pp_guidelines_ltcf.pdf (scroll down to page 344 for the beginning of guidance for §483.25(l)).
 Id. 386 (“1) wandering; 2) poor self-care; 3) restlessness; 4) impaired memory; 5) mild anxiety; 6) insomnia; 7) unsociability; 8) inattention or indifference to surroundings; 9) fidgeting; 10) nervousness; 11) uncooperativeness; or 12) verbal expressions or behavior that are not due to the conditions listed under ‘indications‘ and do not represent a danger to the resident or others”).
 Jeremy Olson, “Drugs often a shortcut for care; Antipsychotics can calm nursing home patients, but also can be misused,” Pioneer Press (Nov. 29, 2008).
 Senate Bill No. 303, http://www.mass.gov/legis/bills/senate/186/st00pdf/st00303.pdf.
 CANHR, Toxic Medicine: What You Should Know to Fight the Misuse of Psychoactive Drugs in California Nursing Homes (Jan. 2010), http://www.canhr.org/reports/2010/Toxic_Medicine.pdf.
 Joanne Kaldy, “Overused Antipsychotics Remain an LTC Challenge; Profession is working to reduce use of drugs,” Caring for the Ages (publication of the American Medical Directors Association), Vol. 10, No. 12 (Dec. 2009), http://download.journals.elsevierhealth.com/pdfs/journals/1526-4114/PIIS1526411409603140.pdf.