A decade ago, the FDA issued a black-box warning about the increased mortality risk associated with atypical antipsychotics used to treat dementia-related psychosis; the warning was extended in 2008 to include typical antipsychotics (www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124830.htm).Since that time, the evidence has been conflicting about the safety of antipsychotics in the elderly. A case-control study found that the mortality risk was increased an estimated 2-4% with typical or atypical antipsychotic use (Maust et al. JAMA Psychiatry 2015;72:438-445). A meta-analysis of 23 atypical antipsychotic studies found no evidence of increased mortality (Tan et al. Alzheimers Res Ther 2015;7:20). A separate meta-analysis of 17 trials failed to show an increased rate of mortality in elderly patients with dementia or delirium treated with typical or atypical antipsychotics (Hulshof et al. J Am Med Dir Assoc 2015; epublished April 28, 2015).
The black-box warning may have had at least two unintended consequences. A retrospective study found that in the non-institutionalized elderly population with dementia, there has been an increased use of psychotropic medications such as benzodiazepines (Singh & Nayak. J Pharm Pract 2015; epublished April 27, 2015).
Secondly, observational studies in Denmark have reported that as antipsychotic use has declined, the use of opioids has increased (Jensen-Dahm et al. EAN 2015; abstract P1106). For the period 2000-2013, the prevalence of antipsychotic drug use in elderly subjects with dementia declined from 31.3% to 20.1%. During the same period, the use of opioids increased from 24.2% to 33.8%. These same trends were seen in elderly subjects without dementia: antipsychotic use decreased from 4.5% to 2.8%, and opioid use increased from 14.9% to 17.2%. While higher opioid use may be due to a better awareness of the importance of adequate pain relief in the elderly, the authors suggested that some clinicians may be using opioids to manage neuropsychiatric symptoms as an alternative to antipsychotics.
Comment
Dr. Catherine Brodeur: These results help us to keep in mind that almost every medication has side effects and that it is mandatory – especially in a geriatric population – to assess the risks and benefits of each drug. This careful analysis must be done by appropriately diagnosing the patient’s conditions and by taking into account the comorbidities of the patient – such as cardiovascular disease, falls, and renal failure – when choosing a medication.