Treatment Of Late-life Depression Research Articles

17. Predictors of Remission After Repetitive Transcranial Magnetic Stimulation for the Treatment of Late-Life Depression

17. Predictors of Remission After Repetitive Transcranial Magnetic Stimulation for the Treatment of Late-Life Depression

Research status and global trends of late-life depression from 2004 to 2023: bibliometric analysis.

Global research hotspots and future research trends in the neurobiological mechanisms of late-life depression (LLD) as well as its diagnosis and treatment are not yet clear. This study profiled the current state of global research on LLD and predicted future research trends in the field. Literature with the subject term LLD was retrieved from the Web of Science Core Collection, and CiteSpace software was used to perform econometric and co-occurrence analyses. The results were visualized using CiteSpace, VOSviewer, and other software packages. In total, 10,570 publications were included in the analysis. Publications on LLD have shown an increasing trend since 2004. The United States and the University of California had the highest number of publications, followed consecutively by China and England, making these countries and institutions the most influential in the field. Reynolds, Charles F. was the author with the most publications. The International Journal of Geriatric Psychiatry was the journal with the most articles and citations. According to the co-occurrence analysis and keyword/citation burst analysis, cognitive impairment, brain network dysfunction, vascular disease, and treatment of LLD were research hotspots. Late-life depression has attracted increasing attention from researchers, with the number of publications increasing annually. However, many questions remain unaddressed in this field, such as the relationship between LLD and cognitive impairment and dementia, or the impact of vascular factors and brain network dysfunction on LLD. Additionally, the treatment of patients with LLD is currently a clinical challenge. The results of this study will help researchers find suitable research partners and journals, as well as predict future hotspots.

Translating Research into Practice: Useful Scientific Advances in the Prevention and Treatment of Late-Life Depression, Bipolar Disorder, and Anxiety to Help Get Your Patients Well

To address the gap between science and implementation, the presenters, international known for their work in late-life mood and anxiety disorders, will contextualize advances in clinical care and provide the audience with advice about how to implement emerging evidence into their clinical programs.Dr. Okereke will provide an overview of the framework of prevention science developed by the National Academy of Medicine. This framework includes indicated, selective, and universal approaches to prevention, and provides a set of guiding principles for developing and applying interventions to prevent depression. She will address prevention trials targeting changes in nutritional, behavioral, and lifestyle factors which may play an important role in reducing the overall burden of depression in older adults.Dr. Gildengers will speak about Bipolar disorder in late-life and provide an overview of the International Society for Bipolar Disorders (ISBD) task force to advance healthcare for older adult bipolar disorder (OABD). This task force established the Global Aging & Geriatrics Experiments in Bipolar Database (GAGE-BD), an effort to combine international datasets into a unified database. GAGE-BD has facilitated research investigations in OABD, addressing a host of topics, including symptom severity in OABD, antipsychotic treatment, and long-term effects of lithium. Dr. Gildengers will review recent research in OABD focusing on reports from the ISBD task force on OABD and GAGE-BD and address the implications for treatment.Dr. Lenze will speak about depression treatment in late-life with a focus on both effectiveness of treatments as well as safety issues of particular relevance for late-life such as falls and cognitive health. He will describe how, over the past decade, several new studies have enhanced our knowledge about safety and effectiveness of antidepressant strategies and share how it is now possible to advance a treatment algorithm based on an understanding of the benefits and risks of antidepressant monotherapies and augmentation strategies. This algorithm includes starting with simple straightforward medications (SSRIs, mirtazapine), then to more complex multi-modal medications (SNRIs, vortioxetine) and then to augmentation strategies (aripiprazole) and interventional strategies (ketamine, TMS, ECT). Dr. Lenze will present the evidence for these strategies and make recommendations about the place of each strategy in a treatment algorithm. He will also discuss the place of precision medicine in choosing an antidepressant based on an individual patient's phenotype.Dr. Andreescu will provide an update on late-life anxiety disorders. She will describe the relationship between anxiety syndromes and several major diseases of aging including cardiovascular, autoimmune diseases, and Alzheimer's Disease and related dementias. As anxiety disorders have the highest lifetime prevalence of any psychiatric illness, Dr. Andreescu will teach the audience how anxiety and its phenotypes potentially represent a highly prevalent and modifiable risk factor for diseases of aging. In this presentation, she will discuss the fluidity of anxiety phenotypes throughout the lifespan, current evidence-based treatment options, and emerging evidence for new treatments for late-life anxiety.Dr. Karp will integrate the main themes from each of the presentations into a call for action for future research and clinical care priorities. There will be ample time for audience engagement and discussion.

Novel Approaches to Assessment and Treatment of Late-life Depression

Depression in late life is common and associated with suffering, reduced quality of life, increased risk of disability, cardiac, cerebrovascular, peripheral diseases, suicidality, all-cause mortality, and economic burden. Many older adults face significant access barriers to mental health services and often remain undiagnosed and untreated. When treatments are considered for late-life depression, antidepressants often have modest efficacy, and older adults prefer alternative approaches. Novel technologies including ecological momentary assessments using mobile devices and machine learning models, can guide the development of scalable and rapid assessments of late-life depression. Further, new therapeutic approaches, such as transcranial direct current stimulation and machine-learning guided psychotherapies, may improve efficacy and provide an alternative to existing therapies. In this session we will present three studies that leverage novel therapeutics and technologies to improve assessment and treatment of late-life depression. We will present findings of research studies in late-life depression and cognitive dysfunction, describe clinical implications. and discuss how findings can be implemented to improve the standard of care in community settings.

Cognitive Outcomes After Antidepressant Pharmacotherapy for Late-Life Depression: A Systematic Review and Meta-Analysis.

The authors evaluated whether treatment of late-life depression (LLD) with antidepressants leads to changes in cognitive function. A systematic review and meta-analysis of prospective studies of antidepressant pharmacotherapy for adults age 50 or older (or mean age of 65 or older) with LLD was conducted. MEDLINE, EMBASE, and PsycInfo were searched through December 31, 2022. The primary outcome was a change on cognitive test scores from baseline to after treatment. Secondary outcomes included the effects of specific medications and the associations between changes in depressive symptoms and cognitive test scores. Participants with bipolar disorder, psychotic depression, dementia, or neurological disease were excluded. Findings from all eligible studies were synthesized at a descriptive level, and a random-effects model was used to pool the results for meta-analysis. Twenty-two studies were included. Thirteen of 19 studies showed an improvement on at least one cognitive test after antidepressant pharmacotherapy, with the most robust evidence for the memory and learning (nine of 16 studies) and processing speed (seven of 10 studies) domains and for sertraline (all five studies). Improvements in depressive symptoms were associated with improvement in cognitive test scores in six of seven relevant studies. The meta-analysis (eight studies; N=493) revealed a statistically significant overall improvement in memory and learning (five studies: effect size=0.254, 95% CI=0.103-0.404, SE=0.077); no statistically significant changes were seen in other cognitive domains. The evaluated risk of publication bias was low. Antidepressant pharmacotherapy of LLD appears to improve certain domains of cognitive function, particularly memory and learning. This effect may be mediated by an improvement in depressive symptoms. Studies comparing individuals receiving pharmacotherapy with untreated control participants are needed.

Cost-effectiveness of behavioral activation compared to treatment as usual for depressed older adults in primary care: A cluster randomized controlled trial

IntroductionDepression in older adults is associated with decreased quality of life and increased utilization of healthcare services. Behavioral activation (BA) is an effective treatment for late-life depression, but the cost-effectiveness compared to treatment as usual (TAU) is unknown. MethodsAn economic evaluation was performed alongside a cluster randomized controlled multicenter trial including 161 older adults (≥65 years) with moderate to severe depressive symptoms (PHQ-9 ≥ 10). Outcome measures were depression (response on the QIDS-SR), quality-adjusted life-years (QALYs) and societal costs. Missing data were imputed using multiple imputation. Cost and effect differences were estimated using bivariate linear regression models, and statistical uncertainty was estimated with bootstrapping. Cost-effectiveness acceptability curves showed the probability of cost-effectiveness at different ceiling ratios. ResultsSocietal costs were statistically non-significantly lower in BA compared to TAU (mean difference (MD) -€485, 95 % CI -3861 to 2792). There were no significant differences in response on the QIDS-SR (MD 0.085, 95 % CI -0.015 to 0.19), and QALYs (MD 0.026, 95 % CI -0.0037 to 0.055). On average, BA was dominant over TAU (i.e., more effective and less expensive), although the probability of dominance was only 0.60 from the societal perspective and 0.85 from the health care perspective for both QIDS-SR response and QALYs. DiscussionAlthough the results suggest that BA is dominant over TAU, there was considerable uncertainty surrounding the cost-effectiveness estimates which precludes firm conclusions.

Effect of computerized cognitive training on mood, cognition, and serum brain-derived neurotrophic factor level in late-life depression - a pilot randomized controlled trial.

The aim of this pilot randomized controlled trial was to test the feasibility of a computerized cognitive training targeting executive dysfunction in late-life depression and to investigate its impact on mood, cognition, and brain-derived neurotrophic factor (BDNF) levels. A total of 28 community-living Chinese individuals aged 55-75 with moderate-to-severe depression and cognitive symptoms (but without mild cognitive impairment or dementia) were recruited from a community centre in Hong Kong. Participants were randomly allocated to either the experimental (receiving computerized cognitive training) or the control group (receiving computer-based health education). Both programs lasted for one hour and were conducted twice a week for 6 weeks at the community centre. We assessed mood using the Hamilton Rating Scale for Depression (HAM-D) and Patient Health Questionaire-9 (PHQ-9), cognition using the Montreal Cognitive Assessment (MoCA), and serum BDNF levels at baseline and follow-up. We performed repeated measures analysis of variance to compare the differences in outcome changes between groups and correlation analysis to test if changes in mood and cognition correlated with changes in BDNF level. Our sample had a mean age of 66.8 (SD = 5.3) years, a mean HAM-D score of 19.4 (SD = 7.5), and a mean PHQ-9 score of 18.0 (SD = 6.3). No adverse effects were reported. Significant differences were observed between the experimental and control groups in changes in HAM-D (-8.4 vs. -2.9; group difference = -5.5; p = 0.01), PHQ-9 (-6.6 vs. -0.6; -6.0; p < 0.001), MoCA (1.4 vs. -1.3; 2.7; p = 0.001), and serum BDNF levels (in pg/ml; 2088.3 vs. -3277.4; 5365.6; p = 0.02). Additionally, changes in HAM-D, PHQ-9, and MoCA scores correlated significantly with changes in BDNF level. With computerized cognitive training improving mood and cognition and increasing serum BDNF levels in 6 weeks, it may serve as a safe and effective evidence-based alternative or adjuvant treatment for late-life depression. https://www.chictr.org.cn/indexEN.html, identifier ChiCTR1900027029.

S12: Recent advances in therapies for late-life neuropsychiatric disorder

Symposium OverviewThis international symposium combining experts from Canada, Australia and the USA and supported by the American Association for Geriatric Psychiatry will present an update on the recent advances in therapeutic interventions for late life mood and cognitive disorders, including late life depression, anxiety and apathy associated with dementia, and preventive strategies including mind-body interventions. Four leaders of the field will present the summary of novel studies: starting with Dr. Benoit Mulsant (CA) presenting the results of the recently completed OPTIMUM study of novel strategies optimizing treatment of late-life treatment resistant depression. He will be followed by Dr. Krista Lanctot’ (CA) update on novel therapies for apathy associated with Alzheimer’s disease, and Dr Nancy Pachana (AU) will present on non-pharmacological approaches to treatment of anxiety associated with neurodegenerative disorders. Finally, Dr. Helen Lavretsky (USA) will present on the recent studies of mind-body therapies used to treat and prevent late life depression and cognitive decline, along with the discussion of the underlying neurobiological mechanisms. The panel will conclude with a brief discussion of future directions in the development of therapeutic interventions.Treatment-resistant depression in late life has been understudied and is lacking evidence supporting augmentation or switching strategies. Recently completed OPTIMUM multi-site study (funded by the PCORI) sought to compare effectiveness of augmentation strategies (bupropion or aripiprazole) to switch to bupropion, in the first step of 1-week acute treatment followed by randomization into the 2nd step of augmentation with Lithium or switch to nortriptyline. The augmentation strategies in the first step produced the most robust response compared to switching, and did not differ in the 2nd step. Primary outcomes included remission rates and wellbeing measures. A discussion of future directions will be provided at the end of this presentation.In those with Alzheimer’s disease, apathy is common and associated with decreased quality of life, increased risk of decline and increased mortality. As such, apathy is increasingly recognized as an important treatment target. Recent advances in diagnosis and treatment will be reviewed.In this presentation, several methodological issues will be discussed, such the importance and prevalence of apathy in Alzheimer’s disease (AD); current diagnostic criteria for apathy in neurocognitive disorders, and will present the results of recent pharmacologic interventions for apathy in AD.In this presentation, new focused and innovative treatments for anxiety in persons with Alzheimer's and Parkinson's disease with co-morbid anxiety will be discussed. Anxiety is common in Alzheimer's Disease and Parkinson's disease and contributes to increased disability and poorer quality of life. Yet only a small fraction of such patients received any form of treatment for mental health issues. Non-pharmacological approaches to address anxiety are advantageous in these populations. Research on tailored CBT and innovations such as virtual reality approaches for these groups will be discussed.Standard pharmacological therapies for treatment of late life depression offer limited efficacy with the downside of adverse events and drug-drug interaction. Novel strategies are needed for more effective and safe treatment and prevention strategies for mood and cognitive disorders in late life. This presentation will focus on the recently completed studies of Tai Chi for treatment of late life depression, and yoga for prevention of cognitive decline in older women at risk for Alzheimer’s disease. Neural and peripheral biomarkers of treatment response will be described. Future directions in mind-body therapies research will be outlined.

Improving social reward responsivity and social connectedness in psychotherapies for late-life depression: Engage & Connect as an example

Psychotherapies are effective in reducing late-life depression. Yet, about half of patients remain depressed at treatment end. Advances in neuroscience can inform simplified interventions that target key brain networks impacted by depression. Behavioral activation therapies that increase social connectedness may improve social reward responsivity and alter abnormalities of the Positive Valence System (PVS). Engage & Connect is an example for a scalable and simple neuroscience-informed psychotherapy, aimed to improve PVS functions and social reward responsivity by increasing engagement in rewarding social activities. Interventions that improve social reward responsivity can be promising first-line treatments for late-life depression in the community.

Late life depression and concepts of aging: an emerging paradigm.

Late life depression (LLD) is an emerging challenge, and recognized as a significant barrier to long-term healthy aging. Viewed within the context of the medical/biological model, advances in brain sciences over the last several decades have led to a deeper understanding of the biology of LLD. These advances in current knowledge include the description of aging brain pathophysiology; the biology and biochemistry of neurotransmitters; the correspondence between changes in neurological structure, function, and neural network; the description of neural, hormonal and inflammatory biomarkers; and identification of typical phenotypic subtypes of LLD. Despite these advances, current treatment of LLD, which remains largely pharmacological with accompanying cognitive and behavioral interventions, has poor success rate for long-term remission among older people. A wider perspective, in keeping with several emerging aging concepts, is suggested as an alternative framework within which to view LLD. A growing body of research supports the important role in LLD of frailty, resilience, intrinsic capacity, and functional integrity. Similarly, important social determinants need to be addressed in the etiology of LLD, rooted largely in negative stereotypes of aging, with consequent repercussions of reduced participation and inclusion, growing social isolation, with loss of identity, meaning and hope. This perspective suggests the importance of a wider integrative conceptualization of depression, set against a background of emerging aging concepts.

Depressive and Biopsychosocial Frailty Phenotypes: Impact on Late-life Cognitive Disorders.

In older age, frailty is a detrimental transitional status of the aging process featuring an increased susceptibility to stressors defined by a clinical reduction of homoeostatic reserves. Multidimensional frailty phenotypes have been associated with all-cause dementia, mild cognitive impairment (MCI), Alzheimer's disease (AD), AD neuropathology, vascular dementia, and non-AD dementias. In the present article, we reviewed current evidence on the existing links among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders, also examining common pathways and mechanisms underlying these links. The depressive frailty phenotype suggested by the construct of late-life depression (LLD) plus physical frailty is poorly operationalized. The biopsychosocial frailty phenotype, with its coexistent biological/physical and psychosocial dimensions, defines a biological aging status and includes motivational, emotional, and socioeconomic domains. Shared biological pathways/substrates among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders are hypothesized to be inflammatory and cardiometabolic processes, together with multimorbidity, loneliness, mitochondrial dysfunction, dopaminergic neurotransmission, specific personality traits, lack of subjective/objective social support, and neuroendocrine dysregulation. The cognitive frailty phenotype, combining frailty and cognitive impairment, may be a risk factor for LLD and vice versa, and a construct of depressive frailty linking physical frailty and LLD may be a good dementia predictor. Frailty assessment may enable clinicians to better target the pharmacological and psychological treatment of LLD. Given the epidemiological links of biopsychosocial frailty with dementia and MCI, multidomain interventions might contribute to delay the onset of late-life cognitive disorders and other adverse health-related outcomes, such as institutionalization, more frequent hospitalization, disability, and mortality.

Brain morphometric features predict depression symptom phenotypes in late-life depression using a deep learning model.

Our objective was to use deep learning models to identify underlying brain regions associated with depression symptom phenotypes in late-life depression (LLD). Diagnosed with LLD (N = 116) and enrolled in a prospective treatment study. Cross-sectional. Structural magnetic resonance imaging (sMRI) was used to predict five depression symptom phenotypes from the Hamilton and MADRS depression scales previously derived from factor analysis: (1) Anhedonia, (2) Suicidality, (3) Appetite, (4) Sleep Disturbance, and (5) Anxiety. Our deep learning model was deployed to predict each factor score via learning deep feature representations from 3D sMRI patches in 34 a priori regions-of-interests (ROIs). ROI-level prediction accuracy was used to identify the most discriminative brain regions associated with prediction of factor scores representing each of the five symptom phenotypes. Factor-level results found significant predictive models for Anxiety and Suicidality factors. ROI-level results suggest the most LLD-associated discriminative regions in predicting all five symptom factors were located in the anterior cingulate and orbital frontal cortex. We validated the effectiveness of using deep learning approaches on sMRI for predicting depression symptom phenotypes in LLD. We were able to identify deep embedded local morphological differences in symptom phenotypes in the brains of those with LLD, which is promising for symptom-targeted treatment of LLD. Future research with machine learning models integrating multimodal imaging and clinical data can provide additional discriminative information.

Effect of prior pharmacotherapy on remission with sequential bilateral theta-burst versus standard bilateral repetitive transcranial magnetic stimulation in treatment-resistant late-life depression.

Repetitive transcranial magnetic stimulation (rTMS) is used for treatment of late-life depression. In the FOUR-D study, sequential bilateral theta-burst stimulation (TBS) had comparable remission rates to standard bilateral rTMS. Data were analysed from the FOUR-D trial to compare remission rates between two types of rTMS based on the number and class of prior medication trials. The remission rate was higher in participants with ≤1 previous trial (43.9%) than in participants with 2 previous trials (26.5%) or ≥3 previous trials (24.6%; χ² = 6.36, d.f. = 2, P = 0.04). Utilising rTMS earlier in late-life depression may lead to better outcomes.

Application of interpersonal psychotherapy for late-life depression in China: A case report.

Interpersonal psychotherapy (IPT) is an effective treatment for late-life depression, but little is known about its acceptability and efficacy in Chinese patients. This case report describes the use of IPT in a depressed elderly Chinese man. The patient was a 79-year-old widower who lives alone in a large city in China. This was his first contact with a mental health specialist. His wife died one ago, and his only child lives in the United States with her husband and children. Due to the COVID-19 pandemic, his daughter could not visit him, and his usual social interactions decreased, leaving him feeling isolated, lonely, and depressed. He was diagnosed with a major depressive episode and initially prescribed venlafaxine. However, he failed to show an adequate response to medication and the side effects were intolerable. He was switched to a low dose of Duloxetine (60 mg) combined with IPT. The patient's baseline score on the 17-item Hamilton depression rating scale (HAM-D) was 29, suggesting severe levels of depression. He received 12 sessions of IPT. Role transition was the focus of therapy. Although the patient expressed discomfort in therapy, he developed a good rapport with the therapist and was compliant with treatment. Clinical recovery was achieved at the end of acute IPT treatment (HAM-D score = 1). Response to IPT was excellent in this elderly patient, but several points should be noted. First, mental health-related stigma in China can affect treatment engagement. Second, older Chinese are reluctant to speak openly about their personal experiences and feelings. Hence, repeated emphasis on the principles of confidentiality in psychotherapy and forming a strong therapeutic alliance are important. Third, the "empty-nest" household is an emergent phenomenon in China. Helping elderly Chinese navigate changes in traditional Chinese living arrangements and negotiate filial piety with offspring who have moved away are important issues to address in therapy.

Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic.

Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in β-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD.

Does acupuncture treatment have satisfactory clinical efficacy for late-life depression? A systematic review and meta-analysis

ObjectiveThis systematic review and meta-analysis aimed to assess the clinical efficacy of acupuncture in late-life depression (LLD). MethodsA comprehensive search of seven electronic databases was conducted from inception to November 2022, including the Cochrane Library, PubMed, Embase, CNKI, VIP, CBM and the Wan Fang database. All data analysis were conducted by Revman 5.3. ResultsA total of nine RCTs involving 603 participants were included. The meta-analysis results showed that acupuncture combined with antidepressants significantly reduced HAMD scores (MD, −3.69 [95% CI, −5.11 to −2.27], I2 =74%) and a significantly higher cure rate (RR, 1.11 [95% CI, 1.01 to 1.22], I2 = 0%) compared with antidepressants alone. However, no significant difference was found between acupuncture and antidepressants in reducing HAMD scores and improving clinical outcomes. ConclusionsAcupuncture combined or not combined with antidepressants is an effective and safe treatment for LLD.

You Don't Know Nicotine: Novel Applications of Nicotinic Therapeutics in Aging

Overall AbstractNicotine binds to nicotinic cholinergic receptors in the brain and the periphery. These receptors are ligand-gated ion channels that modulate other neurotransmitter systems and have important roles in cognitive and emotional functioning. Recent advances have expanded the understanding of how stimulation or blockade of nicotinic receptors affects brain activity, cortical networks, and behavior. While nicotine has been mostly thought of as a substance of abuse connected to tobacco smoking, the potential exists for utilizing nicotine and/or nicotinic stimulation as a therapeutic agent for the treatment of a variety of brain disorders. This symposium will present recent advances in the understanding of how nicotine and nicotinic drugs affect the brain and explore the possible utilization of nicotine for age-related brain disorders. While nicotinic therapeutics has a history dating back to the 1920s, work began in earnest in the 1980s with examining nicotine in Alzheimer's disease. This continued with the development of receptor-selective nicotinic agonists targeted towards Alzheimer’ disease, ADHD, and schizophrenia. These efforts failed, in part because of limited understanding of the appropriate brain system neural targets as well as lack of clarity as to whether the drugs engaged these targets in a meaningful way.Recent research has significantly expanded our understanding of the neural circuitry affected by nicotine and nicotinic stimulation and better human and animal models have offered new insights into the potential for nicotine therapeutics in areas as disparate as hearing loss and stress response mechanisms. Nicotine is now being investigated for its potential in age-related disorders including memory impairment, late life depression, cognitive impairment following cancer treatment and COVID, and age-related hearing loss. The symposium will examine how the effects of nicotine on cognitive functioning differ between older versus younger individuals to explore how nicotinic stimulation benefits may be age specific. We will also present the background and progress of the MIND study, a multi-center nicotine treatment study for mild cognitive impairment, the largest and longest nicotine study of non-smokers ever conducted. New clinical and neural evidence for nicotine as an augmentation treatment for late life depression and the cognitive deficits that accompany this condition will be discussed. Finally, the use of translational animal-human models for discerning the potential beneficial effects of nicotine and the potential for combination therapies to enhance the beneficial effects of nicotine will be presented. These studies of nicotine have broad clinical and scientific significance. If the hypotheses are validated, this will support a novel, broadly available, and inexpensive repurposed intervention for age-related brain disorders and would encourage early treatment to improve symptoms, retard progression of cognitive impairment or improve mood, and lead to combined trials with other agents for brain disorders of aging.

Changes in cognitive function following antidepressant treatment for late-life depression: a systematic review and meta-analysis

Changes in cognitive function following antidepressant treatment for late-life depression: a systematic review and meta-analysis

Therapy Strategies for Late-life Depression: A Review

Depression in the elderly requires different treatment options because therapies that are commonly used for depression in younger patients show different effects later in life. Treatment options for late-life depression (LLD) are summarized in this article. A literature search in Medline/PubMed performed in June 2020 identified 83 relevant studies. Pharmacotherapy with selective serotonin reuptake inhibitors can be an effective first-line treatment in LLD, but >50% of elderly patients do not adequately respond. Switching to other selective serotonin reuptake inhibitors or augmenting with mood stabilizers or antipsychotics is often effective in achieving a therapeutic benefit. Severely depressed patients with a high risk of suicidal behavior can be treated with electroconvulsive therapy. Psychotherapy provides a measurable benefit alone and when combined with medication. LLD remains an underrepresented domain in research. Paucity of data concerning the effect of specific therapies for LLD, heterogeneity in the quality of study designs, overinterpretation of results from meta-analyses, and discrepancies between study results and guideline recommendations were often noted. Treating LLD is complex, but there are several treatment options with good efficacy and tolerability. Some novel pharmaceuticals also show promise as potential antidepressants, but evidence for their efficacy and safety is still limited and based on only a few trials conducted to date.

Transcranial direct current stimulation effects in late life depression: A meta-analysis of individual participant data

• tDCS showed a modest but non-null effect in improving depressive symptoms in late life depression • Acceptability was high for tDCS treatment in late life depression • tDCS is a potential new treatment for late life depression • Large scale, randomised controlled trials of tDCS treatment in late life depression are required Late life depression (LLD) refers to major depressive disorder (MDD) in adults over 65 years. LLD is associated with high morbidity and poor treatment outcomes. Transcranial direct current stimulation (tDCS) is a novel treatment for MDD. Efficacy in LLD though is unclear. Our aim was to investigate tDCS efficacy by pooling randomised controlled trials (RCT) in an individual participant data meta-analysis. Databases were searched for sham controlled RCTs of tDCS in MDD and bipolar depression. Individual participant data (IPD) were requested. Primary outcome was change in depressive symptoms. Bayesian multilevel modelling meta-analysis was conducted with individual participants nested within studies. 6 RCTs were eligible, consisting of 43 participants (22 women), mean age 69.2 years. Active anodal tDCS over left dorsolateral prefrontal cortex (n=19) was associated with an improvement in depressive severity, effect size 0.14 (95% credible interval [-0.44;0.15]) as compared to sham tDCS, which was not statistically significant. There was an 82% probability that tDCS treatment has a modest but non-null effect in improving depressive symptoms. Acceptability was high with no significant differences in discontinuation rates between active and sham groups. The total sample size was small, limiting power. In LLD, tDCS demonstrates a modest but non-null effect in improving depressive symptoms. Acceptability was high as measured by discontinuation rates. tDCS is a potential novel treatment option in LLD, though large scale RCTs in LLD are required to investigate this important clinical application.