Pharmacological and clinical profile of newer antidepressants: implications for
the treatment of elderly patients.
Author(s): Dolder C, Nelson M, Stump A.
Affiliation(s): Wingate University School of Pharmacy, North Carolina 28174, USA.
cdolder@wingate.edu
Publication date & source: 2010, Drugs Aging. , 27(8):625-40
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.
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