Antidepressants are among the most commonly prescribed psychotropic agents for older patients. In particular, there has been a dramatic increase in the frequency at which antidepressants are prescribed to older nursing home patients. Specifically, antidepressant use has increased from 21.9% in 1996 to 47.5% in 2006.1 Of potential concern is that antidepressants are associated with an increased risk for potentially clinically significant adverse drug events (ADEs) in the elderly such as falls and fractures.2 The increased risk of ADEs might be due in part to dosing that does not take into account known age-related changes in antidepressant pharmacokinetics and/or drug-drug interactions (DDIs).3–4 Indeed a recently published study in 877 older nursing home patients showed that 43.1% of antidepressant prescribing for those with depression was potentially inappropriate.5 In particular, dosage problems were seen in 8.8% and DDIs in 25.9%. This latter point is important, as DDIs may be more common in older adults due to the greater number of medications needed to treat persons with multiple comorbid conditions.5
Thus prescribers are faced with a tension that requires that they consider the potential benefits and harms with the use of antidepressants in older patients. Therefore clinicians need accurate up to date pharmacotherapy information sources to correctly dose antidepressants and avoid potential DDIs with antidepressants. One potential source of pharmacotherapy information is the Food and Drug Administration (FDA) approved package inserts (PIs) for marketed antidepressants. However, previous work has shown that PIs for medications commonly used in hospitalized older adults rarely contain comprehensive information about age-related changes in pharmacokinetics.6 Moreover, two separate studies showed that only a minority of potentially clinically significant DDIs appear in the PI compared to other evidence-based sources.7,8 To the best of our knowledge, no study has compared antidepressant PI’s with the evidence-based primary scientific literature regarding the completeness of information about geriatric pharmacokinetics and DDIs.
Given this background, the objective of this study is to synthesize and contrast information in the PI versus that found in the scientific literature regarding antidepressants age-related changes in systemic clearance and potential pharmacokinetic DDIs.