About 25 percent of people with dementia living in either a community setting or long-term care facility receive cholinesterase inhibitors, a government-funded study found.

Researchers also discovered that use of atypical (second generation) antipsychotics, given for off-label treatment of behavioral symptoms associated with dementia, was as high as 21 percent among LTC residents, but about 5 percent among those in the community.

The Agency for Healthcare Research and Quality recently issued a report of the study, which analyzed data from a 2002 survey of 12,697 Medicare beneficiaries. Of those surveyed, 11,593 lived in the community and 1,104 resided in long-term care settings, almost two-thirds of which were nursing homes. The overall prevalence of dementia within the community was 5.1 percent and in LTC facilities it was 57.2 percent.

The findings appear amidst growing concerns about the prevalence of antipsychotic use in nursing homes and the increased mortality and other serious side effects associated with the drugs. Several states, including Alaska, Arkansas and California, have sued manufacturers for off-label marketing of the drugs and Congress has launched investigations of off-label marketing practices.

The AHRQ study, conducted by a team of researchers from the University of Maryland at Baltimore, looked at the prevalence of both approved dementia drugs and antipsychotics used off-label.

FDA has approved five drugs for treatment of dementia symptoms - four cholinesterase inhibitors and memantine (Forest's Namenda ). The authors note that memantine is not included in the data since it was not approved until October 2003.

Aricept Is Drug Of Choice For Dementia

The authors found that 24.7 percent of dementia cases in the community and 26.3 percent in long term care facilities received prescriptions for donepezil (Pfizer/Eisai's Aricept ), galantamine (Johnson & Johnson's Razadyne ) or rivistagmine (Novartis' Exelon ).

Aricept was the most frequently utilized cholinesterase inhibitor, with 19.7 percent of dementia patients in the community and 18 percent in LTC facilities using the drug. Galantamine and rivistagmine were rarely used in the community and were only slightly more common in LTC settings.

The fourth approved drug in that class, tacrine (Sciele's Cognex ) is rarely prescribed because of its side effects and was not mentioned in the study.

The researchers said the similar utilization rates in both settings were unexpected since the primary indication for the drugs is treatment of mild-to-moderate dementia and it is reasonable to assume those in institutionalized settings have more severe dementia. Aricept received approval for moderate to severe dementia in 2006.

"However, in the absence of treatments specifically approved for severe dementia during our study time frame, physicians may have been reluctant to remove patients from these medications even as their disease worsened, given the absence of other treatments for dementia, potential for decline if discontinued, and no clear guideline about when to discontinue," the authors state.

The Alzheimer's Association says the drugs, which work by increasing levels of acetylcholine, a chemical messenger involved in memory and other thought processes, are of limited value.

"In clinical trials of all three cholinesterase inhibitors, people taking the medications performed better on memory and thinking tests than those taking placebo," the association states in a fact sheet. "The degree of benefit was small, however, and more than half of recipients showed no improvement at all."

Race Is Factor In Treatment

The AHRQ study also found that use of cholinesterase inhibitors was highest among those who are white and among those who have supplemental coverage other than Medicaid. Twenty-six percent of whites in the community setting and 27.4 percent of those in LTC facilities received cholinesterase inhibitors. The comparable statistics for blacks was 19.5 percent and 20.6 percent.

Researchers also analyzed the use of antipsychotics for treatment of behavioral symptoms associated with dementia. They found that use of atypical antipsychotics, especially risperidone (J&J's Risperdal ), olanzapine (Lilly's Zyprexa ), and quetiapine (AstraZeneca's Seroquel ) was much higher in LTC residents (21 percent, 11.9 percent and 7.1 percent, respectively) than in the community. The typical antipsychotic haloperidol (J&J's Haldol and generics) was rarely prescribed for dementia residents in LTC facilities.

Antipsychotics Increase Serious Events Threefold

A separate study on use of antipsychotics in older adults with dementia was published in the May 26 issue of the Archives of Internal Medicine. The authors found that first generation antipsychotics were associated with a greater risk of hospitalization or death than second generation drugs.

Community-dwelling adults with dementia who began taking an antipsychotic drug within the past 30 days were 3.2 times more likely to experience a serious adverse event that led to hospitalization or death than those who did not receive such treatment.

Those receiving a conventional antipsychotic (haloperidol, loxapine or thioridazine) were 3.8 times more likely to experience such a serious event within 30 days of starting therapy.

Among those in nursing homes, patients receiving an atypical antipsychotic were 1.9 times more likely to experience a serious event while those receiving a conventional antipsychotic were 2.4 times more likely to do so.

The study evaluated Ontario residents 66 years and older who received a diagnosis of dementia and a prescription for an antipsychotic drug between April 1, 1997 and March 31, 2004.

The authors identified 20,682 matched older adults with dementia living in the community and 20,559 matched individuals living in a nursing home between April 1, 1997 and March 31, 2004.

Lead author Paula Rochon, University of Toronto, said in an interview that this study is unique in that it looked at all serious events associated with antipsychotic use, including extrapyramidal symptoms, cerebrovascular events, falls and hip fractures, as well as death.

"What jumped out a little from the prescriber's perspective," she said, is the importance of knowing the spectrum of serious events associated with the drugs and that serious things can happen quickly even with short-term use.

Among 6,894 community-dwelling older adults receiving atypical antipsychotic therapy, 960, or 13.9 percent, experienced a serious event and 186, or 2.7, percent died. In the nursing home group, of the 6,853 receiving an antipsychotic, 645, or 9.4 percent, experienced a serious event and 355, or 5.2 percent, died.

Rochon said the study did not pick up on all the risks from these drugs since she and her colleagues only looked at events 30 days after initiation of therapy and many adverse events in nursing home residents can be managed without hospitalization.

Mortality Risks Scrutinized

The risks associated with the drugs have been known for years. In 2005, FDA issued a public health advisory that use of atypical antipsychotic medications in elderly patients with dementia increases mortality. The agency also required manufacturers to add a "black box" warning to their labeling (¹ Also see "Antipsychotic Boxed Warning Will Caution Against Off-Label Use In Dementia" - Pink Sheet, 18 April, 2005., p. 5).

The off-label use of antipsychotics in dementia has sparked numerous lawsuits, congressional inquiries and government investigations.

At a House hearing last year, FDA's David Graham said that a back of the envelope calculation indicates there are probably 15,000 elderly people in nursing homes dying each year from off-label use of antipsychotics (² [A#00690080004], p. 8).

However, Rochon said there is a place for the drugs. "In the dementia context there is a role for managing people with behavior" that is difficult or endangers others, she said. But in many instances there are better ways to manage people.

"We feel - and a lot of others feel - that they are overprescribed," she said. She and her colleagues recommend the drugs be prescribed with caution, even for short-term therapy.

- Brenda Sandburg (b.sandburg@elsevier.com)

Antipsychotics Commonly Used Off-Label By Dementia Patients, AHRQ Finds

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