Moderators of Outcome in Late-Life Depression: A Patient-Level Meta-Analysis

Nelson, J. Craig; Delucchi, Kevin; Schneider, Lon S.

doi:10.1176/appi.ajp.2012.12070927

Cited by 70 publications

(66 citation statements)

References 70 publications

(70 reference statements)

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“…As expected, the non-responders had higher GDS-15 and HDRS-21 scores at follow-up (p < 0.001), but also at baseline, suggesting a deeper severity in symptoms was already present before the treatment (Nelson et al, 2013;Saghafi et al, 2007). Age, gender, SSRI subtype, and baseline cognitive evaluation were not associated with the treatment response (Table 1).…”

Section: Discussionsupporting

confidence: 57%

Role of the serotonin transporter gene locus in the response to SSRI treatment of major depressive disorder in late life

et al. 2015

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It has been suggested that the serotonin or 5-hydroxytriptamine (5-HT) transporter (5-HTT) and its gene-linked polymorphic region (5-HTTLPR) are selective serotonin reuptake inhibitor (SSRI) response modulators in late-life depression (LLD), and particularly in late-life major depressive disorder (MDD). Previous studies differed in design and results. Our study aimed to investigate the solute carrier family 6 (neurotransmitter transporter and serotonin) member 4 (SLC6A4) gene locus, encoding 5-HTT and SSRI treatment response in late-life MDD. For a prospective cohort study, we enrolled 234 patients with late-life MDD to be treated with escitalopram, sertraline, paroxetine or citalopram for 6 months. The SLC6A4 polymorphisms rs4795541 (5-HTTLPR), rs140701 and rs3813034 genotypes spanning the SLC6A4 locus were investigated in blinded fashion. No placebo group was included. We assessed responder or non-responder phenotypes according to a reduction in the 21-item version of the Hamilton Depression Rating Scale (HDRS-21) score of ⩾ 50%. At follow-up, 30% of the late-life MDD patients were non-responders to SSRI treatment. No time-course of symptoms and responses was made. A poor response was associated with a higher baseline HDRS-21 score. We observed a significant over-representation of the rs4795541-S allele in the responder patients (0.436 versus 0.321; p = 0.023). The single S-allele dose-additive effect had OR = 1.74 (95% CI 1.12-2.69) in the additive regression model. Our findings suggested a possible influence of 5-HTTLPR on the SSRI response in patients with late-life MDD, which is potentially useful in identifying the subgroups of LLD patients whom need a different pharmacological approach.

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Section: Discussionsupporting

confidence: 57%

Role of the serotonin transporter gene locus in the response to SSRI treatment of major depressive disorder in late life

et al. 2015

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“…129 A meta-analysis of moderators of treatment response in LLD suggests older adults with longer illness duration and moderate to severe depression benefit from antidepressants compared to placebo, whereas short illness duration does not show antidepressant response. 130 Furthermore, executive dysfunction, especially in the subdomains of planning and organization, has been associated with poor antidepressant treatment response in LLD, which may be a factor in trial heterogeneity. 131 One can speculate that vascular depression, associated with executive dysfunction, may be more resistant to traditional pharmacotherapeutic approaches, and may be related to depressive syndromes that are in fact early manifestations of dementia.…”

Section: What Is the Pharmacological Approach To Lld?mentioning

confidence: 99%

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

et al. 2016

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Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. This section on ''Special Populations'' is the sixth of six guidelines articles.Results: Recent studies inform the treatment of MDD in children and adolescents, pregnant and breastfeeding women, women in perimenopause or menopause, and the elderly. Evidence for efficacy of treatments in these populations is more limited than for the general adult population, however, and risks of treatment in these groups are often poorly studied and reported. Conclusions: Despite the limited evidence base, extant data and clinical experience suggest that each of these special populations can benefit from the systematic application of treatment guidelines for treatment of MDD.

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“…Depression results in more years lived with a disability compared with any other disease, and also carries increased risks of suicide, medical comorbidities, and family caregiver burden (Casten et al, 1999;Garcia-Pena et al, 2013;Katon et al, 2010;Mulsant et al, 2006;Nelson et al, 2013). Unfortunately, LLD has a high treatment failure rate (ie 40-60%) with current first-line agents (Lebowitz et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

Khalaf

Edelman

Tudorascu

et al. 2015

Neuropsychopharmacol

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White matter hyperintensities (WMHs) have been shown to be associated with the development of late-life depression (LLD) and eventual treatment outcomes. This study sought to investigate longitudinal WMH changes in patients with LLD during a 12-week antidepressant treatment course. Forty-seven depressed elderly patients were included in this analysis. All depressed subjects started pharmacological treatment for depression shortly after a baseline magnetic resonance imaging (MRI) scan. At 12 weeks, patients underwent a follow-up MRI scan, and were categorized as either treatment remitters (n = 23) or non-remitters (n = 24). Among all patients, there was as a significant increase in WMHs over 12 weeks (t(46) = 2.36, P = 0.02). When patients were stratified by remission status, non-remitters demonstrated a significant increase in WMHs (t(23) = 2.17, P = 0.04), but this was not observed in remitters (t(22) = 1.09, P = 0.29). Other markers of brain integrity were also investigated including whole brain gray matter volume, hippocampal volume, and fractional anisotropy. No significant differences were observed in any of these markers during treatment, including when patients were stratified based on remission status. These results add to existing literature showing the association between WMH accumulation and LLD treatment outcomes. Moreover, this is the first study to demonstrate similar findings over a short interval (ie 12 weeks), which corresponds to the typical length of an antidepressant trial. These findings serve to highlight the acute interplay of cerebrovascular ischemic disease and LLD.

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Moderators of Outcome in Late-Life Depression: A Patient-Level Meta-Analysis

Abstract: Older patients with a long illness duration and moderate to severe depression appear to benefit from antidepressants as compared with placebo. Antidepressants do not appear to be effective for older patients with short illness duration.

Cited by 70 publications

References 70 publications

Role of the serotonin transporter gene locus in the response to SSRI treatment of major depressive disorder in late life

Role of the serotonin transporter gene locus in the response to SSRI treatment of major depressive disorder in late life

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

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