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

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 Unpublished trials, trials examining nonpharmacologic interventions, and papers reporting post hoc analyses were not included in this review unless they provided new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.

Venlafaxine versus nortriptyline in the treatment of elderly depressed inpatients: a randomised, double‐blind, controlled trial

“…First of all, our study population included many patients with severe, often psychotic depression and many patients with severe physical illnesses, two well-known predictors of poor response. The majority of the trials in the elderly are outpatient trials which excluded psychotic patients and patients with common comorbid physical disorders (Taylor and Doraiswamy, 2004). However, two RCTs in depressed older patients with physical illnesses did find that efficacy of antidepressants was not influenced by the presence of comorbid physical illness (Evans et al, 1997;Sheik et al, 2004).…”

“…Depression in the elderly is often untreated or undertreated (Wang et al, 2005), despite the fact that antidepressants have been shown to be efficacious in elderly patients in 28 placebocontrolled double-blind randomised trials (Mittmann et al, 1997;McCusker et al, 1998;Wilson et al, 2001;Taylor and Doraiswamy, 2004). Moreover, there are doubts about the applicability of the results of these trials in actual practice as in most studies patients with common comorbid disorders were excluded (Taylor and Doraiswamy, 2004). Consequently information is lacking about the more complex cases of elderly depressed patients, as found in inpatient wards.…”

Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder

“…Prior antidepressant drug trials have shown a high rate of placebo response (36,37), which often takes the form of a clinically significant response (>50% reduction in symptoms) during the first week of treatment. For this reason, we performed an exploratory analysis in which we examined the subset of patients who did not show this early response.…”

Evidence-Based Pharmacologic Interventions for Geriatric Depression

“…This review focuses on recent geriatric studies examining the comparative efficacy of SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs). The reader is referred elsewhere to recent meta-analyses [43][44][45][46] and systematic reviews [47][48][49] for comprehensive assessments of the effectiveness of TCAs and other agents in the treatment of geriatric depression [46].…”