Pharmacological and Clinical Profile of Newer Antidepressants Implications for the Treatment of Elderly Patients

The pharmacological treatment of older adults with major depressive disorder presents a variety of challenges, including a relative lack of high quality studies designed to measure the efficacy and safety of antidepressants specific to this patient population. Gaining a clear understanding of how to use antidepressants in elderly patients with depression, especially new and widely used agents, would provide valuable insight to clinicians. The purpose of the current article is to review the pharmacology, efficacy and safety of newer antidepressants (i.e. escitalopram, duloxetine and desvenlafaxine) in the treatment of late-life depression. To accomplish this goal, a MEDLINE and PubMed search (1966 February 2010) was conducted for relevant articles. Animal and human studies have clearly demonstrated the effects of desvenlafaxine, duloxetine and escitalopram on monoamine reuptake transporters. The serotonergic and noradrenergic actions of desvenlafaxine and duloxetine may provide for a faster onset of antidepressant activity in the elderly, but more definitive data are needed and the clinical effects of the possible faster onset of action need to be elucidated. Duloxetine and escitalopram are extensively metabolized via cytochrome P450 (CYP) enzymes and the decreased hepatic metabolism present in many older adults should be taken into account when prescribing these medications. Duloxetine possesses the greatest likelihood of producing clinically relevant drug-drug interactions because of its inhibition of CYP2D6. All three agents must also be used cautiously in older adults with poor renal function. In terms of clinical efficacy, 14 prospective published trials involving escitalopram (n = 8) and duloxetine (n = 6) in the treatment of older adults with major depressive disorder were identified. No such studies involving desvenlafaxine were found. Of the five randomized, double-blind, controlled trials, 46% and 37% of antidepressant-treated patients were considered responders and remitters, respectively. In contrast to escitalopram, duloxetine-treated patients experienced improvements in depressive symptoms that more consistently differentiated themselves from the symptoms of placebo-treated patients. Escitalopram and duloxetine were generally well tolerated, but 5-20% and 10-27% of patients, respectively, dropped out because of medication-related adverse effects. Adverse effects experienced by older adults were generally similar to those experienced by younger adults, although indirect comparisons suggest that older adults are more likely to experience dry mouth and constipation with duloxetine and escitalopram, while orthostasis may be more common in older adults prescribed desvenlafaxine. Overall, duloxetine and escitalopram represent modestly effective treatments for late-life depression that are generally well tolerated but do produce a variety of adverse effects. Conclusions regarding desvenlafaxine cannot be made at this time because of a lack of geriatric-specific data.