Beyond the Black Box: What is The Role for Antipsychotics in Dementia?
Year: 2008
Type: article
Abstract: Alzheimer disease (AD) likely affects over 5 million Americans, with this number expected to grow nearly exponentially over the upcoming decades (1). Additionally, millions of Americans are afflicted with other types of dementia. Regardless of the etiology, dementias share certain diagnostic features regarding cognitive and functional decline. Yet, for many patients and their families, the nearly ubiquitous neuropsychiatric symptoms of dementias (e.g. depression, psychosis, aggression, sleep disturbance) are the most problematic aspects of these illnesses, leading to caregiver morbidity, poor patient quality of life, and early patient institutionalization (2). Psychosis, for instance, affects approximately 40% of persons with AD, while agitation occurs in 80% or more of persons with dementia at some point in the illness (3). Although empirical research regarding the treatment of neuropsychiatric manifestations of dementia has been sparse relative to the growing public health significance of this problem, no medication has been FDA-approved for the treatment of these symptoms. Psychotropic medications, especially antipsychotics, have often been used off-label in attempts to ameliorate these symptoms. Yet, this has not been without controversy, as some public perception (at times validated by unfortunate institutional practices) has viewed the use of antipsychotics in dementia as a means of creating “zombies” in order to lighten the work burden of healthcare workers. Nonetheless, psychosis and severe agitation/aggression in dementia can pose significant risks to patients and those around them, such that efforts to treat these symptoms are indeed warranted. While possibly underutilized because of time constraints, reimbursement issues, and lack of training, non-pharmacological strategies to treat aggression and psychosis are appealing alternatives to “knee-jerk” antipsychotic prescriptions; nonetheless, the empirical evidence base for non-pharmacological strategies to control psychosis and/or agitation in dementia remains generally inadequate as well (4).
Adding another layer of complexity onto the use of antipsychotics in treating dementia-related psychosis and/or agitation are the recent FDA black-box warnings regarding atypical agents in this patient population. Beginning with a warning regarding increased risk of “cerebrovascular adverse events including stroke” in dementia patients treated with risperidone versus placebo in 2003, a cascade of warnings for this class of agents has ensued. Similar cerebrovascular black-box warnings have been issued for olanzapine and aripiprazole. While the absolute risk difference was generally 1–2 % between antipsychotic- and placebo-treated patients, the relative risk was approximately two times higher (due to the overall low prevalence of these events in both groups) (5). Perhaps even more daunting, after a meta-analysis of 17 placebo-controlled trials using atypical antipsychotics in dementia, the FDA issued a black-box warning (Table 1) citing an increased risk of mortality for patients receiving atypical antipsychotics (relative risk 1.6–1.7) versus placebo. This warning was applied to atypical antipsychotics as a class, and as with the cerebrovascular risks, the absolute risk difference was between 1–2% (6). Indeed, the public is well-served by evidence-based pharamaco-vigilance that identifies previously unrecognized risks associated with prescription medications, but the FDA data does little to answer the question, “And so, what now?” for the millions of families grappling with these symptoms. Recognizing the limits of answering this question without solid empirical evidence, we attempt to address this question that lingers for clinicians, patients, and caregivers, who must deal with these symptoms while science tries to provide a more definitive answer to this question.
TABLE 1
The FDA Black Box Warnings Regarding Atypical Antipsychotics in Dementia
Source: PubMed
Authors: Thomas W Meeks, Dilip V Jeste
Institution: University of California San Diego
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W73708327