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A Meta-Analysis of Executive Dysfunction and Antidepressant Treatment Response in Late-Life Depression.

ABSTRACT: Depressed older adults with executive dysfunction (ED) may respond poorly to antidepressant treatment. ED is a multifaceted construct and different studies have measured different aspects of ED, making it unclear which aspects predict poor response. Meta-analytic methods were used to determine whether ED predicts poor antidepressant treatment response in late-life depression and to determine which domains of executive functioning are responsible for this relationship.A Medline search was conducted to identify regimented treatment trials contrasting executive functioning between elderly responders and nonresponders; only regimented treatment trials for depressed outpatients aged 50 and older were included. Following the most recent PRISMA guidelines, 25 measures of executive functioning were extracted from eight studies. Six domains were identified: cognitive flexibility, planning and organization, response inhibition, selective attention, verbal fluency, and the Dementia Rating Scale Initiation/Perseveration composite score (DRS I/P). Hedge's g was calculated for each measure of executive functioning. A three-level Bayesian hierarchical linear model (HLM) was used to estimate effect sizes for each domain of executive functioning.The effect of planning and organization was significantly different from zero (Bayesian HLM estimate of domain effect size: 0.91; 95% CI: 0.32-1.58), whereas cognitive flexibility, response inhibition, selective attention, verbal fluency, and the DRS I/P composite score were not.The domain of planning and organization is meaningfully associated with poor antidepressant treatment response in late-life depression. These findings suggest that therapies that focus on planning and organization may provide effective augmentation strategies for antidepressant nonresponders with late-life depression.

SUBMITTER: Pimontel MA

PROVIDER: S-EPMC4928373 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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A Meta-Analysis of Executive Dysfunction and Antidepressant Treatment Response in Late-Life Depression.

Pimontel Monique A MA Rindskopf David D Rutherford Bret R BR Brown Patrick J PJ Roose Steven P SP Sneed Joel R JR

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20150521 1

<h4>Objective</h4>Depressed older adults with executive dysfunction (ED) may respond poorly to antidepressant treatment. ED is a multifaceted construct and different studies have measured different aspects of ED, making it unclear which aspects predict poor response. Meta-analytic methods were used to determine whether ED predicts poor antidepressant treatment response in late-life depression and to determine which domains of executive functioning are responsible for this relationship.<h4>Method ...[more]

PMID: 26282222

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Project description:ImportanceThe etiologic factors of late-life depression are still poorly understood. Recent evidence suggests that microvascular dysfunction is associated with depression, which may have implications for prevention and treatment. However, this association has not been systematically reviewed.ObjectiveTo examine the associations of peripheral and cerebral microvascular dysfunction with late-life depression.Data sourcesA systematic literature search was conducted in MEDLINE and EMBASE for and longitudinal studies published since inception to October 16, 2016, that assessed the associations between microvascular dysfunction and depression.Study selectionThree independent researchers performed the study selection based on consensus. Inclusion criteria were a study population 40 years of age or older, a validated method of detecting depression, and validated measures of microvascular function.Data extraction and synthesisThis systematic review and meta-analysis has been registered at PROSPERO (CRD42016049158) and is reported in accordance with the PRISMA and MOOSE guidelines. Data extraction was performed by an independent researcher.Main outcomes and measuresThe following 5 estimates of microvascular dysfunction were considered in participants with or without depression: plasma markers of endothelial function, albuminuria, measurements of skin and muscle microcirculation, retinal arteriolar and venular diameter, and markers for cerebral small vessel disease. Data are reported as pooled odds ratios (ORs) by use of the generic inverse variance method with the use of random-effects models.ResultsA total of 712 studies were identified; 48 were included in the meta-analysis, of which 8 described longitudinal data. Data from 43?600 participants, 9203 individuals with depression, and 72?441 person-years (mean follow-up, 3.7 years) were available. Higher levels of plasma endothelial biomarkers (soluble intercellular adhesion molecule-1: OR, 1.58; 95% CI, 1.28-1.96), white matter hyperintensities (OR, 1.29; 95% CI, 1.19-1.39), cerebral microbleeds (OR, 1.18; 95% CI, 1.03-1.34), and cerebral (micro)infarctions (OR, 1.30; 95% CI, 1.21-1.39) were associated with depression. Among the studies available, no significant associations of albuminuria and retinal vessel diameters with depression were reported. Longitudinal data showed a significant association of white matter hyperintensities with incident depression (OR, 1.19; 95% CI, 1.09-1.30).Conclusions and relevanceThis meta-analysis shows that both the peripheral and cerebral forms of microvascular dysfunction are associated with higher odds of (incident) late-life depression. This finding may have clinical implications because microvascular dysfunction might provide a potential target for the prevention and treatment of depression.

Project description:Late-life depression frequently co-occurs with cognitive impairment. To inform clinical management of these conditions, we examined the hypotheses that, relative to cognitively normal elders meeting DSM-IV criteria for major depressive disorder, those with cognitive impairment would require greater intensity of pharmacotherapy to reach criteria for antidepressant response and would take longer to respond.Using data from the MTLD-3 study, we conducted a series of secondary analyses examining the implications of cognitive impairment for short-term, open-trial pharmacotherapy of late-life depression (major depressive disorder in individuals 65 years and older). The treatment algorithm consisted of 3 steps: initial treatment with a selective serotonin reuptake inhibitor (SSRI), a switch to a serotonin-norepinephrine reuptake inhibitor (SNRI) if the patient did not respond, and addition of an atypical antipsychotic if the patient did not respond to the SNRI. The first subject entered the protocol in April 2004, and the last subject exited in September 2009. We examined data for participants who completed the acute phase of MTLD-3 as responders and received a cognitive diagnosis (N = 153) based on National Alzheimer's Coordinating Center (NACC) Uniform Data Set criteria. We divided participants into 3 groups on the basis of NACC cognitive diagnosis: no cognitive disorder (n = 74), mild cognitive impairment (n = 60), and dementia (n = 19). For each group, we calculated the proportion of participants requiring first- (SSRI), second- (SNRI), or third-step (add-on atypical antipsychotic) treatment to meet criteria for response (17-Item Hamilton Depression Rating Scale score ? 10 for 3 consecutive weeks). We compared time to response across groups and correlates of nonresponse.The 3 groups did not differ in intensity of pharmacotherapy (P = .68) or time to response (P = .84). Nonresponse was more strongly correlated with longer major depressive episode duration (P = .0015), presence of recurrent depression (P = .002), and younger current age (P = .047), rather than cognitive status (P = .61).Cognitive status does not appear to impact short-term pharmacotherapy response variability in individuals whose depression responds to treatment with open-trial antidepressants delivered in a supportive, university-based medication clinic.

Dataset Information

A Meta-Analysis of Executive Dysfunction and Antidepressant Treatment Response in Late-Life Depression.

Publications

A Meta-Analysis of Executive Dysfunction and Antidepressant Treatment Response in Late-Life Depression.

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