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Efficacy of Second Generation Antidepressants in Late-Life Depression: A Meta-Analysis of the Evidence

https://doi.org/10.1097/01.JGP.0000308883.64832.edGet rights and content

Objective

Second-generation antidepressants are commonly used to treat major depression in late-life. This systematic review and meta-analysis was undertaken to assess the evidence for efficacy of second-generation antidepressants in late-life major depression.

Methods

The Cochrane Library (2006 [3]), MEDLINE (1966 to August 2006), and meeting presentations were searched for trials of second-generation antidepressants (nontricyclics) marketed in the United States. Published and unpublished placebo-controlled randomized clinical trials in outpatients 60 years and older, with nonpsychotic, unipolar major depression were selected. Clinical characteristics and outcomes were extracted. Outcomes were expressed as odds ratios (OR), risk differences, and weighted mean differences.

Results

Ten unique trials (four unpublished) with 13 contrasts met selection criteria. Trials were 6–12 weeks duration, and included 2,377 patients who received active drug and 1,788 received placebo. The ORs by meta-analysis for response and remission were 1.40 (95% confidence interval [CI] 1.24–1.57, z = 5.45, N = 13, p <0.001) and 1.27 (CI 1.12–1.44, z = 3.67, N = 13, p <0.001), respectively, with significant heterogeneity for response and remission among the trials. Mean pooled response rates for antidepressant and placebo were 44.4% and 34.7%, respectively. The OR for response was significantly higher in the 10–12 week trials (OR = 1.73, CI 1.42–2.09, z = 5.51, N = 5, p <0.001) than the 6–8 week trials (OR = 1.22, CI 1.05–1.42, z = 2.60, N = 8, p = 0.01). ORs for discontinuation for any reason and for adverse events were significantly higher with drugs than with placebo.

Conclusions

Antidepressants are more effective than placebo in elderly depressed subjects although effects are modest and vary. Identification of the characteristics of responders and nonresponders will be crucial to improving treatment outcomes.

Section snippets

METHODS

The Cochrane Controlled Trials Register (2006, Issue 3) was searched using terms previously employed by the Cochrane group in a similar search (elder, geriatr, senil, older, old age, late-life, aged, 80-and-over, and depress).6 These terms were supplemented with the terms antidepressants, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, venlafaxine, duloxetine, mirtazapine, bupropion, nefazodone, and trazodone (second-generation antidepressants marketed in the United States).

Search Flow (Results)

The search strategy yielded 192 Cochrane Controlled Trials Register citations and 136 citations from MEDLINE (Fig. 1). The Cochrane search identified 11 placebo-controlled studies and the MEDLINE search 25 placebo-controlled studies. Of these, five trials from the Cochrane search and six trials from the MEDLINE search met inclusion criteria. (The MEDLINE search included all of the Cochrane trials plus one recently published report). A search of abstracts, posters, and slide presentations from

DISCUSSION

Second-generation antidepressants are more effective than placebo during acute treatment of adults 60 years and older with Major Depression in terms of response and remission defined by depression rating scale scores, but the magnitude of this effect is small and variable. The numbers needed to treat calculated from the RDs by meta-analysis were 13 for response and 20 for remission, implying that for every 100 patients treated 8 would show a response and 5 a remission in excess of placebo

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    Dr. Nelson conducted the initial search. Drs. Nelson and Schneider performed the trial selection and data checking. All authors participated in analysis of the data and preparation of the manuscript.

    The authors received no financial support for this meta-analysis.

    This meta-analysis was presented at the Annual Meeting of the AAGP, New Orleans, March 1–4, 2007.

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