Original Article

Neuropsychopharmacology (2004) 29, 2285–2299, advance online publication, 1 September 2004; doi:10.1038/sj.npp.1300550

A Systematic Review of Antidepressant Placebo-Controlled Trials for Geriatric Depression: Limitations of Current Data and Directions for the Future

Warren D Taylor1 and P Murali Doraiswamy1

1Department of Psychiatry, Duke University Medical Center, Durham, NC, USA

Correspondence: Dr WD Taylor, Duke University Medical Center, DUMC Box 3903, Durham, NC 27710, USA. Tel: +1 919 668 7887; Fax: +1 919 681 7668; E-mail: Taylo066@mc.duke.edu

Received 24 October 2003; Revised 12 April 2004; Accepted 14 April 2004; Published online 1 September 2004.

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Abstract

Depression in the elderly is a major public health problem as untreated depression adversely impacts comorbid illnesses. It is important to develop safe and effective antidepressant therapies for older individuals. We performed a systematic review of all published randomized, placebo-controlled antidepressant medication trials in populations over age 55 years. Papers were obtained via MEDLINE (1966–August 2003) and PSYCINFO (1872–August 2003). Unpublished trials, trials examining nonpharmacologic interventions, and papers reporting post hoc analyses were not included in this review unless they provided new insights. A total of 18 placebo-controlled trials examining acute efficacy met our criteria. The combined sample size in these studies was 2252. The mean sample size was 51 (range 20–728) and mean trial duration was 7 weeks. A total of 12 trials examined tricyclic antidepressants (TCAs), five trials examined selective serotonin reuptake inhibitors (SSRIs), two trials examined bupropion, and one trial examined mirtazapine. There were no published trials of venlafaxine or nefazodone. In all, 71.5% of trials reported significantly greater efficacy with drug than placebo. In conclusions, there is a paucity of published controlled antidepressant trials in the elderly. Most published studies examine small sample sizes and do not include common comorbid conditions. Efficacy studies examining relapse prevention are lacking. Large placebo response rates, lack of controlled head to head comparisons, and other methodological design differences make crosstrial comparisons difficult. Large simple studies are urgently needed to address the unmet needs for data on safety and efficacy of antidepressants in this population.

Keywords:

aged, depression, antidepressant therapy, research methodology, review

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