Continuing Treatment of Depression in the Elderly: A Systematic Review and Meta-Analysis of Double-Blinded Randomized Controlled Trials With Antidepressants

doi:10.1097/JGP.0b013e3181ec8085

The American Journal of Geriatric Psychiatry

Volume 19, Issue 3, March 2011, Pages 249-255

https://doi.org/10.1097/JGP.0b013e3181ec8085 Get rights and content

Objective

To establish the efficacy and tolerability of continuing treatment with antidepressants in preventing relapses and recurrences in elderly depressed patients and to analyze differences between tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs).

Design

The authors conducted a systematic literature search to identify all randomized, placebo-controlled, double-blinded clinical trials (RCTs) in elderly patients. Data were pooled from eight double-blinded RCTs of continuation and maintenance treatment in the elderly with 925 participating patients.

Results

The number of patients needed to treat (NNT) for antidepressants to prevent one additional relapse or recurrence was 3 6 (95% confidence interval [CI]: 2.8–4.8). The NNT for TCAs was 2.9 (95% CI: 2.2–4.6), compared with a NNT for SSRIs of 4.2 (95% CI: 3.2–5.9). In the five studies that provide drop out data, 14 of 330 patients (4.2%) using an antidepressant dropped out due to side effects compared with 17 of 330 patients (5.2%) using a placebo (x² = 0.305, df = 1, p = 0.581). Tolerability did not differ between TCAs and SSRIs.

Conclusion

Continuing treatment with anti-depressants in elderly patients is efficacious compared with placebo in preventing relapses and recurrences. Efficacy and tolerability during long-term treatment does not differ between TCAs and SSRIs. (Am J Geriatr Psychiatry 2011; 19:249–255)

Section snippets

METHODS

This systematic review aimed to include all double-blinded RCTs with antidepressant continuation or maintenance treatment of unipolar depression in patients older than 55 years. Trials were eligible for the review if 1) patients were diagnosed as suffering from major depressive disorder according to either Diagnostic and Statistical Manual of Mental Disorders (DSM), International Classification of Diseases (ICD), or Research Diagnostic Criteria (RDC); 2) patients were randomized to continue or

RESULTS

The efficacy of continuation or maintenance treatment in the elderly was investigated in 11 RCTs. We could not find any reference to an unpublished RCT in the elderly. In addition, funnel plots also did not suggest clear evidence for a publication bias. Three RCTs were excluded, one comparing the effect of risperidon augmentation with placebo¹⁰ and one single-blinded RCT comparing the combination of nortriptyline and Electroconvulsive Therapy (ECT) with nortriptyline alone.¹¹ In the third

DISCUSSION

To the best of our knowledge, this is the first meta-analysis of continuation and maintenance treatment with antidepressants in the elderly. The results are in favor of treatment with antidepressants compared with placebo in seven of eight included RCTs. The only negative study is a study that allowed patients to be included with a Mini-Mental State Examination (MMSE) score as low as 12.¹⁷ This may explain the lack of a difference in efficacy between the antidepressant and placebo in this

CONCLUSION

We conclude that the data support the clinical rule to continue an antidepressant after remission irrespective of age of the patient. However, recom-mendations for how long to continue the antidepressants cannot be made based on this meta-analysis alone.

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Cited by (70)

Maintenance Psychotherapies for Older Adults: A Scoping Review
2023, American Journal of Geriatric Psychiatry
Given the chronicity of depression and anxiety disorders in late life, maintenance treatments may have a role in preserving healthy functioning. This study aims to understand the state of the science on maintenance psychotherapies for Black, Asian, and Latinx older adults.
Scoping review.
A priori protocol was prospectively published. Four databases were searched up to December 1, 2021. Eligible studies were conducted in the United States or Puerto Rico and focused on maintenance psychotherapies treating depression, anxiety, or both in adults 60+. Due to the underrepresentation of Black, Asian, and Latinx participants, studies were included irrespective of the participant's racial or ethnic background.
A total of 3,623 unique studies were retrieved, and eight studies were included. Two studies represented randomized clinical trials, and six were studies of post hoc analyses. All studies were from the same research team, had similar maintenance treatments, and focused on depression. Studies included racially homogenous samples (94-98% White). The primary outcome was the recurrence of a major depressive episode. Across studies, maintenance psychotherapy shows promise in preventing the recurrence of depression in some older adults.
Expanding the scope of knowledge from achieving optimal functioning to sustaining those changes in older adults is a significant public health challenge given symptom recurrence. The small body of knowledge on maintenance psychotherapies shows a promising direction in maintaining healthy functioning following recovery from depression. However, opportunities remain to expand the evidence of maintenance psychotherapies with a more significant commitment to the inclusion of diverse populations.
Risk factors for depression in the elderly: An umbrella review of published meta-analyses and systematic reviews
2022, Journal of Affective Disorders
Depression has been identified as one of the leading causes of the disease burden worldwide. Identification of the potential factors that increased or decreased the risk of depression could be important to provide prevention strategies. We aimed to conduct an umbrella review of risk factors for depression in the elderly and assessed the credibility of evidence of the association between each factor and depression.
We searched PubMed and Web of Science from 1990 to April 11, 2021 for articles investigating associations between potential factors and depression. For each association, we recalculated the summary effect size and 95% confidence intervals using random effects models. The 95% prediction interval and between-heterogeneity were also reported. For publication bias, small-study effect and excess of significance bias were assessed.
Twenty-five publications met the inclusion criteria, including twenty-two meta-analyses and three qualitative systematic reviews. Approximately 1,199,927 participants and 82 unique factors were reported. Two factors were rated as convincing evidence and four factors showed highly suggestive evidence. These risk factors were aspirin use, individuals aged 80 years and above, sleep disturbances and persistent sleep disturbances, hearing problem, poor vision, and cardiac disease.
Most studies that we included were of low quality.
We found several risk factors for depression with different levels of evidence, in which aspirin use and individuals aged 80 years and above presented the strongest evidence. Further research is warranted to support other findings from this umbrella review using a large, well-designed cohort study.
Assessment and treatment of major depression in older adults
2019, Handbook of Clinical Neurology
Late life depression is a significant public health problem as well as a burden on patients, their families, and caregivers. There are significant associations of late life depression with medical disorders and cognitive impairment, the latter due to effects of the depression itself or association with dementia. Diagnostic criteria and screening tests have continued to evolve and provide structure and guidelines for assessment. Accurate diagnosis and treatment are of utmost importance to improve quality of life, alleviate suffering, and prevent suicide. A number of effective antidepressant medications are available; combination therapy with these medications and cognitive behavioral therapy appear most efficacious, and maintenance therapy can decrease the chances of remission. A sequence for treatment of late life depression is provided, with strategies for treatment-resistant depression. The relationship of dementia to depression and the interaction of depression with mechanisms of aging are major foci of research.
Associations between age and the course of major depressive disorder: a 2-year longitudinal cohort study
2018, The Lancet Psychiatry
Although there is some evidence that older people might have a poorer course of major depressive disorder (MDD) than younger or middle-aged people, and that age-related course differences might affect the optimisation of MDD treatment, large-scale studies with a broad age range, including consistent course assessments, are needed to properly address this issue. Therefore, we aimed to longitudinally examine whether older age was associated with a poorer naturalistic course trajectory of MDD than that of younger ages and to establish which prognostic—clinical, social, and health—factors could explain this potentially poorer course.
For this longitudinal cohort study, we used baseline and 2-year follow-up data from the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Study of Depression in Older Persons (NESDO) cohorts. People aged between 18 and 88 years, with an MDD diagnosis at baseline, and a valid clinical assessment at 2-year follow-up were included. The primary outcome was the 2-year course of MDD, which was assessed by use of four indicators: having a depression diagnosis (MDD or dysthymia) after 2 years, having a chronic symptom course (depressive symptoms present during 80% or more of the 2-year follow-up period), time to remission, and depression severity change. We used multivariate analyses to examine associations between continuous age and these MDD course indicators. We also examined whether prognostic clinical (eg, comorbid anxiety), social (loneliness and social support), and health (body-mass index, pain, and chronic diseases) factors contributed to the differences in the course of MDD between age groups.
Between 2004–2012, baseline and 2-year follow-up data were obtained for 1042 participants from the NESDA and NESDO cohorts, of whom 690 (66%) were women. Older age was significantly associated with a worse 2-year MDD course for all four indicators (MDD diagnosis: odds ratio [OR] 1·08, 95% CI 1·00–1·17; chronic symptom course: OR 1·24, 1·13–1·35; time to remission: hazard ratio [HR] 0·91, 0·87–0·96; and depression severity change: regression coefficient 1·06, p<0·0001; all per 10-year increase). The course of MDD worsened linearly with age, and people aged 70 years or older had the worst outcomes compared with those of the reference group of people aged 18–29 years (MDD diagnosis: OR 2·02, 95% CI 1·18–3·45; chronic symptom course: OR 3·19, 1·74–5·84; time to remission: HR 0·60, 0·44–0·83; and depression severity change: −12·64 [SD 10·85] in those aged 18–29 years and −5·57 [11·14] in those aged 70 years or older). These results were slightly reduced, but remained mostly significant when adjusting for prognostic clinical, social, and health factors.
Older age was found to be a consistent and important risk factor for a poorer MDD course, which could not be explained by a range of well established risk factors. Further investigation of potential underlying mechanisms—including the effect of cognitive impairment, for example—is needed to prevent the negative consequences of a long-term MDD burden in older people.
Netherlands Organisation for Health Research and Development, Fonds NutsOhra, Stichting tot Steun VCVGZ, NARSAD The Brain and Behaviour Research Fund, and European Union's 7th Framework Programme.
Depression Among Older Adults: A 20-Year Update on Five Common Myths and Misconceptions
2018, American Journal of Geriatric Psychiatry
Citation Excerpt :
Beyond the acute treatment phase, risk of relapse and recurrence raise concerns about durability of antidepressants treatment response. A recent meta-analysis of eight double-blinded randomized controlled trials found support for continuation treatment with antidepressants (tricyclic and selective serotonin reuptake inhibitors) compared with placebo for MDD in older adults.95 Despite this evidence, additional research is needed with longer follow-up periods96 and to compare the efficacy of long-term treatment outcomes for older patients and between both age groups.
Is depression among older adults symptomatically different than younger adults? Is it more common or chronic or difficult to treat? Is depression in late life more likely to be attributed to psychological problems? Twenty-years ago, Dan Blazer, a pioneer known for his groundbreaking work on depression in older adulthood, conducted an important review of the existing literature to refute five commonly held beliefs about depression in late life. Now, two decades later, we call upon selected articles that are representative of our current knowledge to provide an update and identify research priorities. The research consensus spanning the past 20 years suggests that when compared with their younger counterparts, depression in older adults is not more common and is not more often caused by psychological factors. Although some studies have suggested that depression in late life may be symptomatically different and characterized by a more somatic presentation, there is insufficient empirical evidence to conclude that depression presents differently across adulthood. Overall, older adults respond to psychological interventions as well as younger adults, although evidence suggests that antidepressants are less efficacious in late life. Finally, compared with middle-aged adults, depression in older adults is associated with a more chronic course (i.e., higher rate of relapse), which is likely moderated by medical comorbidity. This special article summarizes our current understanding of the nature and treatment of late-life depression and highlights areas of inquiry in need of further study.
Neurochemical correlation between major depressive disorder and neurodegenerative diseases
2016, Life Sciences
Major depressive disorder (MDD) is one of the most prevalent and life-threatening forms of mental illnesses affecting elderly people and has been associated with poor cognitive function. Recent evidence suggests a strong relationship between MDD and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), as well as natural processes of aging. Changes in the neuroplasticity, morphology, and neurotransmission in the brain are seem to be associated to both, MDD and neurodegenerative diseases. In addition, there is evidence that psychological stress and MDD are associated with molecular and cellular signs of accelerated aging. This review will highlight the relationship between MDD, the aging process, and neurodegenerative diseases, emphasizing the neurochemical processes involved.

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Dr. Kok has received research grants from Wyeth and Lundbeck and has received speaker's honoraria from Glaxo-SmithKline, Lundbeck, Pfizer, and Wyeth. Dr. Heeren has received speaker's honoraria from Eli Lilly and Lundbeck. Dr. Nolen has received research grants from Astra

Zeneca, GlaxoSmithKline, and Wyeth; has served as consultant for Astra Zeneca, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, and Pfizer, and has received speaker's honoraria from Astra Zeneca, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Organon, and Pfizer.

No external funding was received for this study or for the publication of the results.

This article has been presented at the 14th IPA congress, September 5, 2009, Montreal, Canada.

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Original ArticleContinuing Treatment of Depression in the Elderly: A Systematic Review and Meta-Analysis of Double-Blinded Randomized Controlled Trials With Antidepressants

Objective

Design

Results

Conclusion

Section snippets

METHODS

RESULTS

DISCUSSION

CONCLUSION

J Affect Disord

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Antidepressant versus placebo for depressed elderly

Cochrane Database Syst Rev

Prognosis of depression in old age compared to middle age: a systematic review of comparative studies

Am J Psychiatry

Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review

Lancet

Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants

Psychiatr Serv

Evidence that patients with single versus recurrent depressive episodes are differentially sensitive to treatment discontinuation: a meta-analysis of placebo-controlled randomized trials

J Clin Psychiatry

Use of antidepressants in late-life depression

Drugs Aging

Assessing the quality of reports of randomized clinical trials: is blinding necessary?

Controlled Clin Trials

Original Article
Continuing Treatment of Depression in the Elderly: A Systematic Review and Meta-Analysis of Double-Blinded Randomized Controlled Trials With Antidepressants