Warning on Antipsychotics Heeded, But What’s the Alternative?

Seniors with dementia received fewer antipsychotic prescriptions after the U.S. Government issued a black box warning in 2005, according to a report in this month’s Archives of General Psychiatry. The warning, which linked the medications to increased mortality in this population, seemed to hasten a trend that had already begun. Analyzing Veterans Affairs (VA) data for more than a quarter million elderly diagnosed with dementia nationwide between 1999 and 2007, “we saw a decline beginning before the black box warning,” said lead author Helen Kales of the University of Michigan, Ann Arbor, in an interview with ARF. “Then, when the black box [warning] came out, there was a significant acceleration in that decline.” Though the study suggests that physicians adjusted their prescribing patterns in response to the federal warning, it did not address the looming issue of how psychiatric symptoms are managed in dementia patients who are not taking antipsychotics.

Neuropsychiatric symptoms afflict many AD patients and are often the main reason why exhausted caregivers decide it is time to institutionalize their loved one. Challenges arise when people start forgetting things, but “if they think their caregivers are poisoning them, it can be really difficult to keep those patients at home,” Kales said. In addition to the cognitive decline, psychiatric behaviors such as aggression, depression, paranoia, and delusions “can appear at any stage of the illness, and it’s often these symptoms that are the most problematic for the family,” she told ARF.

As a geriatric psychiatrist, Kales found herself in a conundrum whenever antipsychotic use came under scrutiny in elderly dementia patients—first around 2002 with safety concerns about increased stroke risk, then in 2005 with the Food and Drug Administration’s black box warning (see ARF related news story). The latter, in particular, was “significant because so many of the folks we see have behavioral issues,” said Kales. “Their families are quite desperate for something to occur, something to change. For a long time, practitioners like myself would turn to antipsychotics.”

Yet after the 2005 black box warning—the strongest action the U.S. Food and Drug Administration can take short of withdrawing a drug—Kales noticed herself becoming “more conservative” about prescribing antipsychotics to her dementia patients. She wondered if fellow physicians were responding to the warning in similar fashion. “You might think it’s a given, but the reality is that there is really no clear alternative agent to the antipsychotics,” Kales said. To complicate matters, an earlier study led by coauthor Lon Schneider, University of Southern California, Los Angeles, called into question the effectiveness of atypical or second-generation antipsychotics (Schneider et al., 2006 and ARF related news story).

In the present study, Kales and colleagues monitored antipsychotic use among 254,564 veterans diagnosed with dementia over an eight-year interval encompassing a no-warning period (1999-2003), an early-warning period (2003-2005), and a black box warning period (2005-2007). They adjusted for the number of dementia patients, which tripled over the study span, and examined, in addition, the use of other psychotropic drugs besides antipsychotics.

When the study began, nearly 18 percent of dementia patients were taking antipsychotics; by the end, that was down to 12 percent. “That is a significant decline in use and, given the size of the study population, had an impact on many patients,” Kales noted. Use of “atypical” antipsychotics, which have better side effect profiles than older ones, increased during the no-warning years, but leveled off in the early-warning period and dropped at roughly the same rate as conventional medications after the black box warning.

The proportion of dementia patients taking non-antipsychotic psychotropics rose after the black box warning from 20 to 25 percent. However, individual drug classes within this group did not seem to show compensatory increases, the authors report. Indeed, the percentage of participants taking all types of psychotropic medications—but excluding cholinesterase inhibitors and memantine—hovered around 40 percent throughout the study. Plus, the rate of growth of cholinesterase inhibitors and memantine slowed in the aftermath of the black box. Mirroring the findings of a recent survey of geriatric physicians (Saad et al., 2010), these trends suggest that doctors turned to antipsychotics less often, but did not seem to compensate for this decrease by prescribing more psychotropics in general.

The study shows how historical and societal forces influence physicians, the good news being the decrease in antipsychotic prescriptions, commented Laura Gitlin, who recently moved to Johns Hopkins University School of Nursing in Baltimore, Maryland.

However, the analysis leaves a number of questions unanswered. “What alternative treatments, if any, were used and were they effective?” Gitlin wrote in an e-mail to ARF. A recent New York Times story described how some nursing homes are going to great lengths to accommodate the whims of their unruly patients. Their solutions include giving residents baby dolls, unlimited chocolate, and other types of individualized attention to a particular patient’s desires. This went into effect in large part due to research suggesting that pleasurable experiences can relieve behavior problems in AD patients. In a randomized trial of nursing home patients in The Netherlands, simply brightening the care facility not only made participants less depressed, but also slowed their cognitive decline and improved daily function (Riemersma-van der Lek et al., 2008 and ARF related news story).

Furthermore, in a recent trial conducted by Gitlin and colleagues, dementia patients and their caregivers reported better quality of life after four months of home visits that identified specific needs and empowered caregivers to help patients manage daily tasks. These and similar interventions appear to provide temporary relief for patients (see ARF related news story on Gitlin et al., 2010).

“Understanding current physician prescribing behaviors is one piece of a larger challenge that involves changing the conversation about dementia care,” Gitlin noted. “We must develop a more holistic and comprehensive approach to managing the disease process over the course of the disease—an approach that identifies and manages comorbidities common in aging individuals with dementia, and which equally attends to sustaining quality of life and person-centered care of the people with dementia and their family members.”—Esther Landhuis

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References

News Citations

  1. More Trouble for Atypical Antipsychotics—Dementia Patients at Risk
  2. Rethinking Antipsychotics for Alzheimer Patients—Again
  3. Research Brief: Beefing Up Circadian Rhythm Helps AD Symptoms
  4. Behavioral Approach Improves Life for Dementia Patients, Caregivers

Paper Citations

  1. Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, Lebowitz BD, Lyketsos CG, Ryan JM, Stroup TS, Sultzer DL, Weintraub D, Lieberman JA, . Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12;355(15):1525-38. PubMed.
  2. Saad M, Cassagnol M, Ahmed E. The impact of FDA's warning on the use of antipsychotics in clinical practice: a survey. Consult Pharm. 2010 Nov;25(11):739-44. PubMed.
  3. Riemersma-van der Lek RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJ, Van Someren EJ. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA. 2008 Jun 11;299(22):2642-55. PubMed.
  4. Gitlin LN, Winter L, Dennis MP, Hodgson N, Hauck WW. A biobehavioral home-based intervention and the well-being of patients with dementia and their caregivers: the COPE randomized trial. JAMA. 2010 Sep 1;304(9):983-91. PubMed.

External Citations

  1. black box warning
  2. New York Times story

Further Reading

Papers

  1. Gitlin LN, Winter L, Dennis MP, Hodgson N, Hauck WW. A biobehavioral home-based intervention and the well-being of patients with dementia and their caregivers: the COPE randomized trial. JAMA. 2010 Sep 1;304(9):983-91. PubMed.
  2. Saad M, Cassagnol M, Ahmed E. The impact of FDA's warning on the use of antipsychotics in clinical practice: a survey. Consult Pharm. 2010 Nov;25(11):739-44. PubMed.
  3. Ayalon L, Gum AM, Feliciano L, Areán PA. Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Arch Intern Med. 2006 Nov 13;166(20):2182-8. PubMed.

Primary Papers

  1. Kales HC, Zivin K, Kim HM, Valenstein M, Chiang C, Ignacio RV, Ignacio R, Ganoczy D, Cunningham F, Schneider LS, Blow FC. Trends in antipsychotic use in dementia 1999-2007. Arch Gen Psychiatry. 2011 Feb;68(2):190-7. PubMed.

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