Antidepressant Studies in People With Depression and Dementia
Objectives: To determine the efficacy of antidepressants in people with depression and dementia.
Design: A systematic review and meta-analysis based on a literature search of Medline and Cochrane Trials Registry for acute-phase, double-blind, placebo-controlled, parallel-design, random-assignment trials of antidepressants marketed in the United States.
Setting: Outpatient clinics, inpatient units, residential settings.
Participants: People with criterion-based diagnoses of dementia and depression.
Measurements: Numbers of participants randomized; baseline and end point depression scale scores; and response, remission, and discontinuation rates were extracted. Random-effects meta-analyses were performed for response and remission rates, change scores using standardized mean differences, and discontinuation rates. Sensitivity analyses were planned to examine effects of depression diagnosis, severity, and trial duration.
Results: Seven trials with 330 participants met selection criteria. The odds ratio (OR) for six trials reporting response rates with antidepressant and placebo was 2.12 (95% confidence interval (CI)=0.95–4.70; Z=1.84, P=.07). The OR for five trials reporting remission rates was 1.97 (95% CI=0.85–4.55; Z=1.59, P=.11). Both analyses demonstrated heterogeneity. The standardized mean difference in trials was 0.29 (95% CI=0.02–0.60, Z=1.86, P=.06). This analysis did not demonstrate significant heterogeneity. Adverse event discontinuation rates (9.0%) were not significantly higher with drug than placebo (6.0%), and were low.
Conclusion: The evidence for antidepressant treatment of people with depression and dementia, although suggestive, does not confirm efficacy. All of the trials were significantly underpowered to detect differences, resulting in inconclusive findings. Variable trial methods, comorbid conditions, and differences in antidepressants employed further confounded findings.
Depression is common in people with dementia. Prevalence estimates vary from 5% to 40% for major depression and 5% to 15% for minor depression or symptoms of depression. Depression not only adds to suffering, disability, suicide risk, and mortality rates, but is also associated with greater functional impairment in people with dementia.
In people with late-life depression without dementia, it has recently been reported that antidepressants are effective but that the advantage over placebo is modest. Specifically, the odds ratio (OR) was 1.40 (95% confidence interval (CI)=1.24–1.57; P<.001), pooled response rates were 44.4% versus 34.7%, and the number needed to treat (NNT) was 13. Antidepressants have been the usual treatment for people with depression and dementia. Traditional psychotherapies that depend on adequate memory may be less effective in people with dementia, so evidence-based psychotherapies may not be applicable. As a consequence, it is important to determine whether antidepressants are effective in the treatment of depression in people with dementia. Two prior systematic reviews and meta-analyses were published in people with depression and dementia in 2002 and 2007, but the number of trials published at that point and the limited data provided in the controlled trials limited those analyses.
The current meta-analysis, reviews all trials of antidepressants for treatment of depression in people with dementia. Trials published since the previous reviews were included. Reported rates of response and remission were focused on, and symptom change with treatment was also examined. Sensitivity analyses were planned to examine the effects of diagnostic variability, depression severity, and trial duration on response.
Abstract and Introduction
Abstract
Objectives: To determine the efficacy of antidepressants in people with depression and dementia.
Design: A systematic review and meta-analysis based on a literature search of Medline and Cochrane Trials Registry for acute-phase, double-blind, placebo-controlled, parallel-design, random-assignment trials of antidepressants marketed in the United States.
Setting: Outpatient clinics, inpatient units, residential settings.
Participants: People with criterion-based diagnoses of dementia and depression.
Measurements: Numbers of participants randomized; baseline and end point depression scale scores; and response, remission, and discontinuation rates were extracted. Random-effects meta-analyses were performed for response and remission rates, change scores using standardized mean differences, and discontinuation rates. Sensitivity analyses were planned to examine effects of depression diagnosis, severity, and trial duration.
Results: Seven trials with 330 participants met selection criteria. The odds ratio (OR) for six trials reporting response rates with antidepressant and placebo was 2.12 (95% confidence interval (CI)=0.95–4.70; Z=1.84, P=.07). The OR for five trials reporting remission rates was 1.97 (95% CI=0.85–4.55; Z=1.59, P=.11). Both analyses demonstrated heterogeneity. The standardized mean difference in trials was 0.29 (95% CI=0.02–0.60, Z=1.86, P=.06). This analysis did not demonstrate significant heterogeneity. Adverse event discontinuation rates (9.0%) were not significantly higher with drug than placebo (6.0%), and were low.
Conclusion: The evidence for antidepressant treatment of people with depression and dementia, although suggestive, does not confirm efficacy. All of the trials were significantly underpowered to detect differences, resulting in inconclusive findings. Variable trial methods, comorbid conditions, and differences in antidepressants employed further confounded findings.
Introduction
Depression is common in people with dementia. Prevalence estimates vary from 5% to 40% for major depression and 5% to 15% for minor depression or symptoms of depression. Depression not only adds to suffering, disability, suicide risk, and mortality rates, but is also associated with greater functional impairment in people with dementia.
In people with late-life depression without dementia, it has recently been reported that antidepressants are effective but that the advantage over placebo is modest. Specifically, the odds ratio (OR) was 1.40 (95% confidence interval (CI)=1.24–1.57; P<.001), pooled response rates were 44.4% versus 34.7%, and the number needed to treat (NNT) was 13. Antidepressants have been the usual treatment for people with depression and dementia. Traditional psychotherapies that depend on adequate memory may be less effective in people with dementia, so evidence-based psychotherapies may not be applicable. As a consequence, it is important to determine whether antidepressants are effective in the treatment of depression in people with dementia. Two prior systematic reviews and meta-analyses were published in people with depression and dementia in 2002 and 2007, but the number of trials published at that point and the limited data provided in the controlled trials limited those analyses.
The current meta-analysis, reviews all trials of antidepressants for treatment of depression in people with dementia. Trials published since the previous reviews were included. Reported rates of response and remission were focused on, and symptom change with treatment was also examined. Sensitivity analyses were planned to examine the effects of diagnostic variability, depression severity, and trial duration on response.