Update on Mortality Risk Associated With the Off-label Use of Antipsychotic Medications for Dementia in the Elderly

International authorities began warning health care practitioners about the cerebro- and cardiovascular risks of prescribing antipsychotics for the management of troublesome behaviors in elderly patients with dementia in 2004.^[1] Pooled data analyses suggesting a small but statistically significant risk of stroke and sudden death led FDA to require a boxed warning for the entire drug class in 2008.^{[2,3,4,5,6,7]}

Despite the warnings, antipsychotics continue to be used off-label in this population and as of 2011, nearly one-quarter of all US nursing home residents diagnosed with dementia were receiving an antipsychotic medication.^[8] In an effort to discourage first-line use of antipsychotics for dementia symptoms, both the UK (in 2009)^[9] and the US (in 2012)^[8] have undertaken broad national health initiatives to improve dementia care. Due to limited therapeutic alternatives,^[10] and despite conclusive evidence of low therapeutic efficacy for this indication,^[11,12] neither program met the goal of substantially reducing the prevalence rate of antipsychotic prescriptions in this population.^[13] However, ongoing regulatory scrutiny has spurred clinicians and researchers to seek the lowest-risk strategy for these challenging patients.^[14,15]

The best contemporary risk assessment of antipsychotics has been compiled in a 2011 Agency for Healthcare Research and Quality publication.^[11] Briefly, a preponderance of evidence confirms that there is a slight elevation in risk for all-cause mortality among elderly patients with dementia initiated on antipsychotic therapy. The increased risk is assumed to extend to all members of the class, and the etiology for the effect remains unproven.^[16,17] The current published medical literature is insufficient to quantify a difference between traditional and atypical antipsychotics, but the number needed to harm (NNH) calculated for atypical antipsychotics is 100.^[11] From prescription trends, it is clear that most prescribers prefer atypical antipsychotics over traditional antipsychotics in the setting of dementia-related psychosis.^[14] More specifically, a preponderance of evidence suggests that haloperidol, olanzapine and risperidone are generally associated with a higher risk for adverse outcomes in this population than aripiprazole and quetiapine (see Table 1 and Table 2 ).^[7,11,18]

The America Geriatric Society's 2012 Beers Criteria List recommends avoiding antipsychotics for the behavioral problems of dementia unless non-pharmacological options have failed and the patient represents a threat to self or others.^[19] Consistent with international "best-practice" treatment guidelines, antipsychotic medications should only be used as second-line therapy, at the lowest dose, with monitoring, and for the shortest duration feasible.^{[21,22,23,24]}

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