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Articles   |    
Moderators of Outcome in Late-Life Depression: A Patient-Level Meta-Analysis
J. Craig Nelson, M.D.; Kevin L. Delucchi, Ph.D.; Lon S. Schneider, M.D.
Am J Psychiatry 2013;170:651-659. doi:10.1176/appi.ajp.2012.12070927
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Dr. Nelson has served as a consultant, adviser, or speaker for, received research support or travel support from, or participated in CME for AstraZeneca, Avanir, Bristol-Myers Squibb, Cenestra Health, Corcept, Eli Lilly, Eli Lilly Global, Forest, Health Resources and Services Administration, Labopharm, Lundbeck, Medtronic, Merck, Merck Asia, Mylan/Dey Pharma, NIMH, Orexigen, Otsuka, Otsuka Asia, Pfizer, Sunovion, and Theracos; he has provided expert testimony for Finnegan, Henderson et al. on behalf of Eli Lilly, and he owns stock in Atossa. Dr. Schneider has received consulting fees from AC Immune, Allon, AstraZeneca, Baxter, Biogen-Idec, Chiesi, Elan, Eli Lilly, En Vivo, GlaxoSmithKline, Ibsen, Johnson & Johnson, Lundbeck, Merck, Pfizer, Roche, Takeda, Toyama, and Zinfandel; he and University of Southern California have received research grants from Baxter, Eli Lilly, Genentech, Novartis, and Pfizer. Dr. Delucchi reports no financial relationships with commercial interests.

From the Department of Psychiatry, University of California San Francisco; and the Departments of Psychiatry and Behavioral Sciences and of Neurology, Keck School of Medicine, and the Leonard Davis School of Gerontology, University of Southern California, Los Angeles.

Address correspondence to Dr. Nelson (craign@lppi.ucsf.edu).

Copyright © 2013 by the American Psychiatric Association

Received July 16, 2012; Revised November 08, 2012; Revised December 12, 2012; Accepted December 19, 2012.

Abstract

Objective  The authors sought to identify factors that moderate outcome in late-life major depression and that identify patients for whom antidepressants have clinically meaningful effects.

Method  A previous systematic review identified 10 placebo-controlled trials of second-generation antidepressants in outpatients with major depressive disorder who were age 60 or older. For the present study, the authors obtained from the sponsors of the 10 trials individual patient data, including age, sex, duration of illness (current age minus age at onset), course (single episode or recurrent depression), baseline depression severity, treatment assignment, and outcomes. Logistic regression models were estimated and tested to examine the association of potential moderator variables with treatment response and the treatment group-response interaction.

Results  All moderator variables were collected and documented for seven of the 10 trials (N=2,283). Univariate and multivariate analyses were restricted to these seven trials. Illness duration was the only variable significantly associated with drug-placebo differences in the multivariate model. In patients with an illness duration >10 years, baseline depression severity was also significantly associated with drug-placebo differences. In those with an illness duration >10 years and a Hamilton Depression Rating Scale score ≥21, the drug-placebo difference in response rates was relatively robust (number needed to treat=4). In the remaining patients, the drug-placebo difference in response rates was small (46.3% compared with 41.5%).

Conclusions  Older patients with a long illness duration and moderate to severe depression appear to benefit from antidepressants as compared with placebo. Antidepressants do not appear to be effective for older patients with short illness duration.

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FIGURE 1. Response Rates for Drug and Placebo, by Age, Depression Severity, Illness Duration, Sex, and Course of Illnessa

a Categories are defined by quartiles for age and severity, by tertiles for illness duration, and in terms of single episode or recurrent depression for course. Severity was measured with the 17-item Hamilton Depression Rating Scale (HAM-D). Illness duration was computed as current age minus age at onset. Error bars indicate 95% confidence intervals.

FIGURE 2. Effect Size of Drug-Placebo Differences, by Depression Severity, in Patients With Long Duration of Depressive Illness (>10 Years)a

a Depression severity is defined in quartiles. Illness duration was computed as current age minus age at onset.

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TABLE 1.Patient Characteristics in Randomized Placebo-Controlled Trials of Second-Generation Antidepressants in Late-Life Depression
Table Footer Note

a Studies that had values for all the variables of interest were included in the present analyses; studies that did not collect data for one of the variables of interest were excluded.

Table Footer Note

b Duration of illness was computed as current age minus age at onset.

Table Footer Note

c Depression severity was measured with the 17-item Hamilton Depression Rating Scale.

Table Footer Note

d Course of illness was either single episode or recurrent.

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TABLE 2.Randomized Placebo-Controlled Trials of Second-Generation Antidepressants in Patients 60 Years and Older With Major Depressive Disordera
Table Footer Note

a MMSE=Mini-Mental State Examination; HAMD17, HAMD21, and HAMD24=17-, 21, and 24-item Hamilton Depression Rating Scale; MADRS=Montgomery-Åsberg Depression Rating Scale; CR=controlled release; XL=extended release.

Table Footer Note

b Studies that had values for all the variables of interest were included in the present analyses; studies that did not collect data for one of the variables of interest were excluded.

Table Footer Note

c DSM-III-R and DSM-IV required a 2-week duration of symptoms. Some studies required 4 weeks, as indicated.

Table Footer Note

d Modified intent-to-treat sample with at least one posttreatment rating, last observation carried forward.

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TABLE 3.Analysis of Association of Age, Illness Duration, Course, Sex, and Depression Severity With Response and With Interaction of Treatment Group and Response, Controlling for Study
Table Footer Note

a The treatment group-response interaction reflects the drug-placebo difference.

Table Footer Note

b Age and depression severity were assessed by quartiles.

Table Footer Note

c Duration of illness (computed as current age minus age at onset) was assessed by tertiles.

+

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