Elderly patients are generally more sensitive to medication adverse effects, partly because of age-related changes in pharmacokinetics.25 Adverse events specifically related to the use of antipsychotic medications in elderly patients with dementia have come to light in recent years. Some of the most concerning adverse effects related to these medications are cerebrovascular events.26 The 2003 warning by the FDA referred to cerebrovascular adverse events (stroke, transient ischemic attack), some of which were fatal, in elderly patients with dementia-related psychosis and/or agitation in trials of risperidone(Drug information on risperidone). The manufacturer of risperidone added a warning to the prescribing information with respect to stroke risk in elderly patients with dementia. Similar warnings were later applied to the other atypical antipsychotics, and since 2005, the FDA has required a black box warning for all second-generation antipsychotic medications.
In a meta-analysis, pooled rates of cerebrovascular events were 1.9% in patients treated with atypical antipsychotics compared with 0.9% in patients who received placebo, and the risk of all-cause mortality was approximately 1.6 times greater in the treated patients.17 The first-generation (typical) antipsychotics seem to carry at least the same level of risk, and in 2008, the FDA required a similar warning for these medications.
Rational approach to treatment
The conundrum of treating patients with neuropsychiatric symptoms of Alzheimer disease remains: extremely common symptoms, coupled with attendant morbidities, that lack an effective and safe treatment strategy.
Many clinical situations are not dangerous; therefore, with the idea of “first do no harm” in mind, before consideration of atypical antipsychotics, other interventions should be tried. First, potential organic etiologies of a patient’s behavioral problems should be ruled out. For example, untreated pain or urinary tract infections are common causes for changes in behavior. Nonpharmacological interventions, such as cognitive stimulation, as well as behavioral management paradigms, such as reassuring, repeating and redirecting, looking for antecedents to behaviors and seeing how they can be modulated, and breaking tasks into simpler parts or limiting choices, may all be very helpful. Other interventions that have been tried, although not rigorously studied, include modulation of room lighting and ambient noise levels, aromatherapy, music therapy, pet therapy, art therapy, and structured exercise programs.
