Prescribing antipsychotics in geriatric patients: Focus on dementia

Other clinical data

Observational studies. Most observational studies have confirmed concerns regarding increased mortality in patients with BPSD who take antipsychotics, with FGAs having a higher risk than SGAs^18,31 and SGAs having a higher risk compared with most other psychotropics.³² Three studies that found no increase in mortality with antipsychotics in patients with dementia had methodological issues, including examining prevalence as opposed to new users,^33,34 not controlling for exposure,^10,33,34 power issues,^10,34 not controlling for other psychiatric medications,¹⁰ and varying lengths of follow-up.¹⁰ An FDA black-box warning for FGAs was announced in 2008³⁰ based on 2 observational studies that showed an increased risk of mortality in older adults taking FGAs vs SGAs.^35,36

In terms of specific SGAs, Kales et al³⁷ examined the mortality risk associated with individual antipsychotics using various methods to control for confounding. Among a national sample of >33,000 older veterans with dementia newly started on haloperidol, risperidone, olanzapine, quetiapine, or valproic acid and derivatives (as a nonantipsychotic comparator), the highest mortality across all analyses (intent to treat, exposure, propensity-adjusted) was associated with haloperidol, followed by risperidone and olanzapine, valproic acid, and quetiapine.

Most recently, a retrospective case-control study (90,786 patients age ≥65 with dementia) examined the number needed to harm (NNH; ie, number of patients needed to receive treatment that would result in 1 death) over 180 days following initiation of an FGA or SGA.³⁸ This study found the following NNHs: haloperidol, 26 (95% CI, 15 to 99); risperidone, 27 (95% CI, 19 to 46); olanzapine, 40 (95% CI, 21 to 312); and quetiapine, 50 (95% CI, 30 to 150).³⁸ These results are congruent with a review of observational studies that found the highest risk of mortality was associated with haloperidol and chlorpromazine, and the lowest risk with olanzapine, quetiapine, and ziprasidone.²⁸

Patterns of antipsychotic use in older dementia patients

There are high rates of antipsychotic use in patients with dementia. Before the FDA issued the black-box warning, the Aging Demographics and Memory study found that the rate of antipsychotic use in community (outpatient) older adults with dementia was approximately 19% between 2002 and 2004 in a representative sample of 307 older adults.³⁹ Another study examining trends in community antipsychotic use in the U.S. Department of Veterans Affairs (VA) found that in the 1990s, SGA use was increasing; approximately 18% of outpatients with dementia were taking these agents.⁴⁰ Use of SGAs began to decline in 2003, ahead of the 2005 black-box warning, in tandem with other advisories (eg, diabetes, metabolic syndrome,⁴¹ and stroke risk).^42,43 Olanzapine and risperidone showed declining rates between 2003 and 2005, whereas quetiapine use significantly increased during this period. All 3 SGAs declined after the black-box warning. However, by the end of 2007, the use of SGAs had leveled off to approximately 12% of VA patients with dementia. A recent U.S. Government Accountability Office (GAO) report found that in 2012, 14% of older adult Medicare Part D enrollees with dementia living in the community were prescribed an antipsychotic.⁴⁴

Use in nursing home residents. Because BPSD are one of the main reasons people with dementia are placed in nursing homes, it is not surprising that rates of antipsychotic use are higher in these settings than in the community. Prior to the black-box warning, studies found that 24% to 32% of nursing home residents were treated with antipsychotics.^45-47 A study examining VA nursing homes (n = 133 facilities, n = 3,692 veterans) found that approximately 26% of residents were prescribed antipsychotics in 2004 to 2005.⁴⁸ The Center for Medicare and Medicaid Services (CMS) National Partnership to Improve Dementia Care in Nursing Homes has appeared to lower antipsychotic medication use in nursing homes; the rate decreased from 24% in long-stay nursing home residents nationwide in 2011 to 19% by the end of 2014. Specific to dementia, a 2010 CMS report⁴⁹ indicated that approximately 40% of nursing home residents with cognitive impairment and behavioral issues, without psychosis, received antipsychotics. The GAO data indicated that approximately 33% of older Medicare Part D enrollees with dementia who spent >100 days in a nursing home were prescribed an antipsychotic in 2012.⁴⁴ A recent Canadian study using drug claims data found that overall psychotropic use in patients with dementia remains high, finding that three-fourths of all patients with dementia in long-term care are given at least 1 psychotropic, and up to one-third are prescribed SGAs.⁵⁰ European data similarly show that antipsychotics continue to be prescribed to up to one-third of long-term care residents with dementia, with 7 out of 10 receiving an SGA.¹