Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials.
Abstract
OBJECTIVE
Late-life depression is an important public health issue, given the growing proportion of the elderly relative to the general
population in the developed world. The purpose of this study was to examine the efficacy of antidepressants for the treatment
of major depressive disorder (MDD) in elderly patients.
DATA SOURCES
PubMed/MEDLINE was searched for randomized, double-blind, placebo-controlled trials of antidepressants for treatment of both
adult (nonelderly) MDD (patients aged < 65 years) and late-life MDD (patients aged ≥ 55 years). The search was limited to
articles published between January 1, 1980, and March 3, 2010 (inclusive). The year 1980 was used as a cutoff in our search
to decrease diagnostic variability, since the DSM-III was introduced in 1980. Our search cross-referenced the term placebo
with each of the following antidepressants: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine,
protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine,
isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine,
tianeptine, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine,
and mianserin. We also reviewed the reference lists of all studies identified through the PubMed/MEDLINE search.
STUDY SELECTION
Articles were selected that reported on randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy
for treatment of MDD and that met numerous a priori criteria pertaining to MDD diagnosis criteria, study duration, study design,
drug formulation, original data, age thresholds, primary and secondary outcome measures, and exclusions of other disorders.
Final inclusion of articles was determined by consensus between the authors. Seventy-four articles were found eligible for
inclusion in our analysis (15 late-life MDD trials and 59 adult MDD trials).
RESULTS
Antidepressants were found to be efficacious for late-life MDD (age 55 and older; P < .0001), although there was evidence
for heterogeneity across studies (Q22 = 67.302, P < .001). However, antidepressants were not found to be efficacious in the
subset of studies using age thresholds of 65 years or older (older late-life MDD) (P = .265). Finally, when we controlled
for study design characteristics, antidepressant but not placebo response rates were lower among late-life MDD patients than
among adult MDD patients.
CONCLUSIONS
The present meta-analysis suggests that antidepressants are efficacious in late-life MDD, but significant study heterogeneity
suggests that other factors may contribute to these findings. A secondary analysis raises the possibility that efficacy of
these agents may be reduced in trials involving patients aged 65 years or older. Why antidepressants may be less efficacious
in elderly versus younger subjects remains unclear.
Links
Authors
Tedeschini E, Levkovitz Y, Iovieno N, Ameral VE, Nelson JC, Papakostas GI
Institution
Department of Psychiatry, University of Modena and Reggio Emilia, Modena, Italy. enricoted@hotmail.it
Source
The Journal of clinical psychiatry 72:12 2011 Dec pg 1660-8MeSH
Age FactorsAged
Aging
Antidepressive Agents
Depressive Disorder, Major
Humans
Middle Aged
Randomized Controlled Trials as Topic
Regression Analysis
Treatment Outcome
Pub Type(s)
Journal ArticleMeta-Analysis
Language
eng
PubMed ID
22244025
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