Improvement In Depression Severity Research Articles

Cognitive behavioural therapy for depression, quality of life, and cognitive function in the post-stroke period: systematic review and meta-analysis.

The post-stroke period is associated with a lot of sequelae, including depression, decreased quality of life, and decline of cognitive function. Apart from the pharmacotherapy, it is also important to find a non-pharmacological treatment to relieve the sequelae. Cognitive behavioural therapy (CBT) might be a potential candidate, which can be clarified by a systematic review and meta-analysis. The eligible criteria of enrolled studies in the systematic review and meta-analysis were the randomised clinical trials (RCTs) using CBT to treat post-stroke depression, or with the focus on quality of life or cognitive function in the post-stroke period. The endpoint scores of depression, quality of life, and cognitive function scales were the targeted outcome for the final meta-analysis in the random effects model. Ten RCTs with 432 post-stroke patients receiving CBT and 385 controls were included. The meta-analysis results showed significant improvements in depression severity and quality of life. However, no significant difference between CBT and control groups was found in cognitive function. In addition, significant heterogeneity was derived from the meta-analysis. According to the meta-analysis results, CBT might be beneficial for relieving depression severity and improving quality of life. However, cognitive function might not be influenced by CBT. Further studies with a more consistent CBT design with greater sample sizes should be warranted to clarify and confirm the treatment effects of CBT for post-stroke depression and quality of life.

The rapid antidepressant effectiveness of repeated dose of intravenous ketamine and intranasal esketamine: A post-hoc analysis of pooled real-world data

IntroductionIntravenous ketamine (KET-IV) and intranasal esketamine (ESK-NS) are effective in the acute treatment of Treatment-Resistant Depression (TRD). Studies comparing KET-IV and ESK-NS concerning their action, safety, and tolerability are currently lacking. Materials and methodsWe combined patients' data from two unipolar TRD cohorts that received KET-IV (n = 171) at the Canadian Rapid Treatment Center of Excellence in Toronto, Canada, or ESK-NS (n = 140) at several TRD clinics in Italy. The Quick Inventory for Depression Symptomatology-Self-Report-16/QIDS-SR16 in the KET-IV group and Montgomery-Åsberg Depression Rating Scale/MADRS in the ESK-NS group measured depressive symptoms at baseline (T0) and after the acute treatment phase (T1) (i.e., four infusions of KET-IV and eight administrations of ESK-NS). As different scales were used, the primary outcome was to compare the improvement in depression severity in the two cohorts by measuring effect sizes, response and remission rates. Finally, we compare side effects and discontinuation rates. ResultsAt T1, KET-IV and ESK-NS significantly reduced depressive symptoms (respectively: QIDS-SR16 mean reduction = 5.65, p < 0.001; MADRS mean reduction = 11.41, p = 0.025). KET-IV showed larger effect sizes compared to ESK-NS (1.666 vs. 1.244). KET-IV had higher response rates (36 % vs. 25 %; p = 0.042) but not superior remission rates (13 % vs. 12 %; p = 0.845) than ESK-NS at T1. Despite more reported side effects, KET-IV did not cause more discontinuations for adverse events (4.6 % vs. 2.12 %; p = 0.228) than ESK-NS. ConclusionKET-IV showed a higher short-term antidepressant effect, whereas ESK-NS exhibited lower side effects. Both were generally well tolerated. Future head-to-head studies should consider the long-term efficacy of these treatments.

Low-dose interleukin 2 antidepressant potentiation in unipolar and bipolar depression: Safety, efficacy, and immunological biomarkers

Immune-inflammatory mechanisms are promising targets for antidepressant pharmacology. Immune cell abnormalities have been reported in mood disorders showing a partial T cell defect. Following this line of reasoning we defined an antidepressant potentiation treatment with add-on low-dose interleukin 2 (IL-2). IL-2 is a T-cell growth factor which has proven anti-inflammatory efficacy in autoimmune conditions, increasing thymic production of naïve CD4 + T cells, and possibly correcting the partial T cell defect observed in mood disorders. We performed a single-center, randomised, double-blind, placebo-controlled phase II trial evaluating the safety, clinical efficacy and biological responses of low-dose IL-2 in depressed patients with major depressive (MDD) or bipolar disorder (BD). 36 consecutively recruited inpatients at the Mood Disorder Unit were randomised in a 2:1 ratio to receive either aldesleukin (12 MDD and 12 BD) or placebo (6 MDD and 6 BD). Active treatment significantly potentiated antidepressant response to ongoing SSRI/SNRI treatment in both diagnostic groups, and expanded the population of T regulatory, T helper 2, and percentage of Naive CD4+/CD8 + immune cells. Changes in cell frequences were rapidly induced in the first five days of treatment, and predicted the later improvement of depression severity. No serious adverse effect was observed. This is the first randomised control trial (RCT) evidence supporting the hypothesis that treatment to strengthen the T cell system could be a successful way to correct the immuno-inflammatory abnormalities associated with mood disorders, and potentiate antidepressant response.

Robotic transcranial magnetic stimulation in the treatment of depression: a pilot study

There has been an increasing demand for robotic coil positioning during repetitive transcranial magnetic stimulation (rTMS) treatment. Accurate coil positioning is crucial because rTMS generally targets specific brain regions for both research and clinical application with other reasons such as safety, consistency and reliability and individual variablity. Some previous studies have employed industrial robots or co-robots and showed they can more precisely stimulate the target cortical regions than traditional manual methods. In this study, we not only developed a custom-TMS robot for better TMS coil placement but also analyzed the therapeutic effects on depression. Treatment effects were evaluated by measuring regional cerebral blood flow (rCBF) using single-photon emission computed tomography and depression severity before and after rTMS for the two positioning methods. The rTMS preparation time with our robotic coil placement was reduced by 53% compared with that of the manual method. The position and orientation errors were also significantly reduced from 11.17 mm and 4.06° to 0.94 mm and 0.11°, respectively, confirming the superiority of robotic positioning. The results from clinical and neuroimaging assessments indicated comparable improvements in depression severity and rCBF in the left dorsolateral prefrontal cortex between the robotic and manual rTMS groups. A questionnaire was used to determine the patients’ feelings about the robotic system, including the safety and preparation time. A high safety score indicated good acceptability of robotic rTMS at the clinical site.

Evaluation of major depressive disorder using 7 Tesla phase sensitive neuroimaging before and after mindfulness-based cognitive therapy

ObjectiveWe applied 7 Tesla phase sensitive imaging to evaluate the impact of brain iron levels on depression severity and cognitive function in individuals with major depressive disorder (MDD) treated with mindfulness-based cognitive therapy (MBCT). MethodsSeventeen unmedicated MDD participants underwent MRI, evaluation of depression severity, and cognitive testing before and after receiving MBCT, compared to fourteen healthy controls (HC). Local field shift (LFS) values, measures of brain iron levels, were derived from phase images in the putamen, caudate, globus pallidus (GP), anterior cingulate cortex (ACC) and thalamus. ResultsCompared to the HC group, the MDD group had significantly lower baseline LFS (indicative of higher iron) in the left GP and left putamen and had a higher number of subjects with impairment in a test of information processing speed. In the MDD group, lower LFS values in the left and right ACC, right putamen, right GP, and right thalamus were significantly associated with depression severity; and lower LFS in the right GP was correlated with worse performance on measures of attention. All MBCT participants experienced depression relief. MBCT treatment also significantly improved executive function and attention. MBCT participants with lower baseline LFS values in the right caudate experienced significantly greater improvement in depression severity with treatment; and those with lower LFS values in the right ACC, right caudate, and right GB at baseline performed better on measures of verbal learning and memory after MBCT. ConclusionsOur study highlights the potential contribution of subtle differences in brain iron to MDD symptoms and their successful treatment.

Interpersonal Trauma and Depression Severity Among Individuals With Bipolar Disorder: Findings From the Prechter Longitudinal Study of Bipolar Disorder.

ABSTRACT Background: Experiences of interpersonal trauma, both in childhood and in adulthood, can affect the trajectory of bipolar disorder (BD). However, the degree to which childhood and/or adult trauma impacts the longitudinal trajectory of depression severity among individuals with BD actively receiving treatment remains unclear. Methods: The effects of childhood trauma (Childhood Trauma Questionnaire) and adult trauma (Life Events Checklist) on depression severity (Hamilton Depression Rating Scale) were investigated in a treatment-receiving subsample with BD (DSM-IV) of the Prechter Longitudinal Study of Bipolar Disorder (2005–present). A mixed-effects linear regression model was used to assess the trajectory of depression severity over 4 years. Results: Depression severity was evaluated in 360 participants, of whom 267 (74.8%) reported a history of interpersonal trauma. A history of childhood trauma alone (n = 110) and childhood and adult trauma combined (n = 108)—but not adult trauma alone (n = 49) —were associated with greater depression severity at the 2-year and 6-year follow-up assessments. However, the trajectory of depression severity (ie, change over time) was similar between participants with a history of childhood trauma, those with a history of adult trauma, and those with no history of interpersonal trauma. Interestingly, participants with a history of both types of trauma showed more improvement in depression severity (ie, from year 2 to year 4: β = 1.67, P = .019). Conclusions: Despite actively receiving treatment for BD, participants with a history of interpersonal trauma—particularly childhood trauma—presented with more severe depressive symptoms at several follow-up assessments. Hence, interpersonal trauma may represent an essential treatment target.

Early reduction in irritability is associated with improved outcomes among youth with depression: Findings from the AMOD study

ObjectivesEvaluate whether early improvement in irritability predicts improvement in depression severity in a naturalistic sample of adolescents undergoing pharmacologic treatment for major depressive disorder. MethodsAdolescents (N = 161) aged 13–18 years with a moderate to severe depressive episode were enrolled. Outcome measures included the Children's Depression Rating Scale-Revised (CDRS-R), Quick Inventory of Depressive Symptomatology (QIDS-A17), and Clinical Global Impression scale (CGI). Paired t-tests were used to estimate the change in irritability items from baseline to week-4, and Cohen's d effect sizes were computed. Separate linear regression analyses with CDRS-R, QIDS-A17, and CGI at week-8 as the dependent variables and baseline levels of irritability and baseline-to-week-4 changes in irritability as independent variables of interest were conducted. These analyses were repeated after controlling for overall depression severity (minus the irritability item) at baseline and baseline to week-4 change. ResultsGreater baseline to week-4 reduction in irritability was associated with lower levels of CDRS-R, QIDS-A17, and CGI at week-8. These findings were significant for QIDS-A17 and CGI even after controlling for baseline-to-week-4 changes in other depressive symptoms. LimitationsThe single item evaluation of irritability reduced assessment reliability in the absence of validated measures of irritability. ConclusionsEarly reduction in irritability is strongly associated with better outcomes in depressed youths, regardless of baseline depression severity. Further research is needed to quantify the burden of irritability, explore it as a tool for measurement-based care, and to develop targeted treatments for irritability.

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.

The effect of two cognitive therapies on subjective wellbeing of individuals with depression: results from a randomised controlled trial

Background Despite the burden associated to depression, current standards of care are still limited in scope and effectiveness. In addition, therapy outcomes have frequently focused solely on symptoms, leaving patients’ wellbeing relatively unaddressed. Aims The objective of this study was to test whether two cognitive therapies increased subjective wellbeing in a sample of adults diagnosed with a depressive disorder, additionally assessing the relationship between this growth and decreases in both depression severity and psychological distress. Methods Data from 116 participants from a randomised controlled trial comparing the efficacy of cognitive behavioural therapy and dilemma-focused therapy were analysed. Multilevel linear models were employed, together with correlational analyses. Results Results showed that both interventions significantly improved wellbeing with moderate to large effect sizes, while no significant differences were found between treatments. In turn, the increase in wellbeing was significantly associated to improvements in depression severity and psychological distress. Conclusions This study sheds light on the complex relationship between happiness and depression, supporting their conceptualisation as related yet independent human experiences, and strengthening subjective wellbeing as a useful outcome for psychological research. Psychotherapy is presented as an effective intervention to enhance wellbeing, even among individuals with severe depressive symptoms.

Effectiveness of L-carnitine Supplementation to Sertraline for Treatment of Major Depressive Disorder: A Double-blind Randomized Placebo-controlled Trial

Objectives: Despite the various treatment approaches proposed for major depressive disorder (MDD), the right treatment protocol for different patients is not the same. Supplementation of L-carnitine to antidepressants has been recommended in some studies; however, different results have been reported. This study aimed to evaluate the effectiveness of adding L-carnitine to sertraline in the treatment of patients diagnosed with MDD. Material and Methods: This double-blind randomized controlled trial was conducted on 60 patients with MDD. The severity of the depressive disorder, as the primary research outcome, was assessed using the Beck depression inventory. The intervention group received 1000 mg of daily L-carnitine oral capsule along with 100 mg of sertraline; and the control group received a placebo (oral capsule containing 1000 mg of starch), along with 100 mg of sertraline every day. The primary outcome was assessed at baseline, the 3rd, and the 6th week. Results: Although depression score decreased in both groups over time, the difference between the two groups was not significant (P = 0.634). Three patients reported adverse side effects; however, the difference between the two groups was not significant (P = 0.554). Conclusion: Supplementation of L-carnitine to sertraline in patients with MDD did not show a significant effect on the improvement of depression severity.

Toward a Definition of "No Meaningful Benefit" From Antidepressant Treatment: An Equipercentile Analysis With Cross-Trial Validation Across Multiple Rating Scales.

Background: Many patients with major depressive disorder (MDD) who experience no meaningful benefit (NMB) from antidepressive treatment go undetected. However, there is a lack of consensus on the definition of NMB from antidepressants.Methods: Equipercentile linking was used to identify a threshold for percent change in 17-item Hamilton Depression Rating Scale (HDRS-17) scores that equated with a Clinical Global Impressions-Improvement (CGI-I) score of 3 (minimally improved), a proxy for NMB, after 4 and 8 weeks of citalopram or escitalopram treatment, using data from the Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS). The NMB threshold for the HDRS-17 was validated by equating a CGI-I rating of 3 with percent change values from the clinician- and patient-rated versions of the Quick Inventory of Depressive Symptomatology (QIDS-C and QIDS-SR) using data from PGRN-AMPS and phase 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. This study was conducted between June 2021 and September 2021.Results: In PGRN-AMPS, a 30% improvement in HDRS-17 score corresponded to a CGI-I rating of 3 at 4 and 8 weeks. The 30% improvement threshold was also observed for QIDS-C and QIDS-SR scores in both PGRN-AMPS and STAR*D. Similar results were observed for percent change in HDRS-17 and QIDS-based measures in lower- and higher-severity groups based on a median split of baseline total scores.Conclusions: Improvement in depressive severity of ≤ 30%, as assessed using the HDRS-17, QIDS-C, and QIDS-SR, may validly define NMB from antidepressants during short-term treatment.

A comparison of real-world effectiveness of vortioxetine along the treatment algorithm for major depressive disorder

Objective To evaluate the effectiveness of vortioxetine in major depressive disorder (MDD) when used as a first-line versus second-line treatment or later. Methods This was a post-hoc analysis of three 3-month non-interventional, prospective studies of vortioxetine in MDD – REVIDA (Malaysia, Philippines, Singapore, Thailand), PREVIDA (Pakistan) and TREVIDA (Taiwan). Improvements in depressive symptoms (PHQ-9, CGI-S), cognitive function (PDQ-D) and work productivity (WPAI) were compared between studies, and in a pooled analysis of patients using vortioxetine as first line versus second-line treatment or later. Safety was compared between studies. Results Overall, 798 patients were analyzed (PREVIDA =425, REVIDA =130, TREVIDA =243). Most patients in PREVIDA (60.5%)/REVIDA (57.4%) used vortioxetine as first-line treatment versus TREVIDA (21.8%). Generally, greater improvements from baseline were observed across outcome measures in PREVIDA/REVIDA versus TREVIDA (Month 3, p < 0.0001). Vortioxetine as first-line treatment was associated with greater improvements in depression severity, cognition, functioning outcomes compared to second-line or later users (PHQ-9: -16.1 [6.4] vs -10.8 [8.9]; CGI-S: -2.7 [1.1] vs -2.0 [1.4]; PDQ-D: -29.5 [17.7] vs -18.5 [21.4]; p < 0.0001 at Month 3) as well as greater response (PHQ-9: 88.6% vs 61.5%; p < 0.0001) and remission rates (PHQ-9: 75.4% vs 47.7%; p < 0.0001). No new adverse events were reported outside of the product label. Conclusions In the Asian real-world setting, vortioxetine showed greater improvements in depressive and cognitive symptoms, work functioning, and response and remission rates when used as first-line versus second-line treatment or later. Vortioxetine was well-tolerated irrespective of the study population across Asia.

Use of Telemedicine in Depression Care by Physicians: Scoping Review.

BackgroundDepression is a common disorder, and it creates burdens on people’s mental and physical health as well as societal costs. Although traditional in-person consultations are the usual mode of caring for patients with depression, telemedicine may be well suited to psychiatric assessment and management. Telepsychiatry can be defined as the use of information and communication technologies such as videoconferencing and telephone calls for the care of psychopathologies.ObjectiveThis review aims to evaluate the extent and nature of the existing literature on the use of telemedicine for the care of depression by physicians. This review also aims to examine the effects and perceptions regarding this virtual care and determine how it compares to traditional in-person care.MethodsThe Arksey and O’Malley framework and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines were followed. Relevant articles were identified through a search of three databases (MEDLINE, Cochrane Database of Systematic Reviews, and PsycArticles) on October 11, 2020. The search terms were “(virtual OR telemedicine OR teleconsultation* OR telehealth OR phone* OR webcam* OR telepsychiatry) AND (depress*)”. Eligibility criteria were applied to select studies about the use of telemedicine for the care of patients with depression specifically by physicians. An Excel file (Microsoft Corporation) was used to chart data from all included articles.ResultsThe search resulted in the identification of 28 articles, and all 13 nonreview studies were analyzed in detail. Most nonreview studies were conducted in the United States during the last decade. Most telemedicine programs were led by psychiatrists, and the average study population size was 135. In all applicable studies, telepsychiatry tended to perform at least as well as in-person care regarding improvement in depression severity, patient satisfaction, quality of life, functioning, cost-effectiveness, and most other perceptions and variables. Cultural sensitivity and collaborative care were part of the design of some telemedicine programs.ConclusionsAdditional randomized, high-quality studies are recommended to evaluate various outcomes of the use of telemedicine for depression care, including depression variables, perceptions, health care outcomes and other outcomes. Studies should be conducted in various clinical contexts, including primary care. Telepsychiatry is a promising modality of care for patients suffering from depression.

Cognitive Behavioral Therapy to Sustain the Antidepressant Effects of Ketamine in Treatment-Resistant Depression: A Randomized Clinical Trial

Introduction: Ketamine has emerged as a rapid-acting antidepressant. While ongoing treatment can prevent relapse, concerns exist regarding long-term exposure. Objective: We conducted a randomized trial to examine the feasibility and efficacy of cognitive behavioral therapy (CBT) following intravenous ketamine in treatment-resistant depression (TRD). Methods: Subjects with TRD were recruited and treated with 6 intravenous infusions of ketamine over 3 weeks. Subjects who experienced a clinical response (≥50% improvement in depression severity) were then randomized to receiving CBT or treatment as usual (TAU) for an additional 14 weeks, using a sequential treatment model. Results: Of the 42 patients who signed consent, 28 patients achieved a response and were randomized to CBT or TAU. When measured using the Montgomery-Asberg Depression Rating Scale (primary outcome measure), the effect size at the end of the study was moderate (Cohen d = 0.65; 95% CI –0.55 to 1.82), though the group-by-time interaction effect was not significant. There was a significant group-by-time interaction as measured by the Quick Inventory of Depressive Symptomatology (F = 4.58; p = 0.033), favoring a greater sustained improvement in the CBT group. This corresponded to a moderate-to-large effect size of the Cohen d = 0.71 (95% CI –0.30 to 1.70) at the end of the study (14 weeks following the last ketamine infusion). In a subset of patients (N = 20) who underwent cognitive testing using the emotional N-back assessments before and after ketamine, ketamine responders showed improvement in the accuracy of emotional N-back (t[8] = 2.33; p < 0.05) whereas nonresponders did not (t[10] <1; p ns). Conclusions: This proof-of-concept study provides preliminary data indicating that CBT may sustain the antidepressant effects of ketamine in TRD. Further study and optimization of this treatment approach in well-powered clinical trials is recommended.

Early changes in neural circuit function engaged by negative emotion and modified by behavioural intervention are associated with depression and problem-solving outcomes: A report from the ENGAGE randomized controlled trial.

BackgroundDepression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity.MethodsThis study (‘ENGAGE’) was a pre-planned element of the randomized controlled trial, ‘RAINBOW’ (ClinicalTrials.gov NCT02246413). 108 depressed patients with obesity were randomized to receive an integrated collaborative care intervention (I-CARE) or usual care. Participants underwent functional neuroimaging using an established facial emotion task at baseline and two months (coinciding with the first two months of intervention focused on problem-solving therapy (‘PST’)). Amygdala, insula and anterior cingulate cortex activation was extracted using pre-planned definitions and standardized methods. The primary health and behavioural outcomes were depression symptom severity and problem-solving ability respectively, assessed at baseline, the main 6-month outcome point and at 12-month follow up. Mediation analyses used an intent-to-treat approach.FindingsPST, relative to usual care, reduced amygdala activation engaged by threat stimuli at two months. This reduction mediated subsequent improvements in depression severity in an intervention-dependent manner. PST did not change insula activation at two months but did temper the strength of the relationship between insula activation and improvements in problem-solving ability.InterpretationThe negative affect circuit may be an important neural target and potential mediator of PST in patients with comorbid obesity.FundingUS National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368

Aerobic Exercise and Stretching as Add-On to Inpatient Treatment for Depression Have No Differential Effects on Stress-Axis Activity, Serum-BDNF, TNF-Alpha and Objective Sleep Measures

(1) Background: While the antidepressant effects of aerobic exercise (AE) are well documented, fewer studies have examined impact of AE as an add-on treatment. Moreover, various effects on neurobiological variables have been suggested. This study examines effects of AE on Cortisol Awakening Reaction (CAR), serum Brain Derived Neurotrophic Factor (sBDNF), Tumor Necrosis Factor alpha (TNF-alpha) and sleep. (2) Methods: Inpatients with moderate-to-severe depression (N = 43) were randomly assigned to the AE or stretching condition (active control) taking place 3x/week for 6 weeks. CAR, sBDNF and TNF-alpha were assessed at baseline, after 2 weeks and post-intervention. The 17-item Hamilton Depression Rating Scale (HDRS17), subjective sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) were obtained at baseline and post-intervention. (3) Results: Stress axis activity decreased in both groups from baseline to post-intervention. sBDNF showed a significant increase over time, whereas the number of awakenings significantly decreased. No significant time by group interactions were detected for any of the study variables. Correlational analyses showed that higher improvements in maximum oxygen capacity (VO2max) from baseline to post-intervention were associated with reduced scores on the HDRS17, PSQI and REM-latency post-intervention. (4) Conclusions: While some neurobiological variables improved during inpatient treatment (CAR, sBDNF), no evidence was found for differential effects between AE and an active control condition (stretching). However, patients in which cardiorespiratory fitness increased showed higher improvements in depression severity and depression-related sleep-parameters.

Default mode network connectivity and treatment response in geriatric depression

<h3>Introduction</h3> Depression is associated with decreased default mode network (DMN) connectivity. Memantine is a non-competitive N-methyl-D-aspartate receptor antagonist that is currently FDA-approved for the treatment of cognitive symptoms in dementia. We evaluated the relationship between changes in DMN connectivity and improvement in depression in a subsample of our parent clinical trial comparing escitalopram/memantine (ESC/MEM) to escitalopram/placebo (ESC/PBO) in older depressed adults (NCT01902004). <h3>Methods</h3> Twenty-six participants with major depression (age >60 years) and subjective memory complaints underwent treatment with ESC/MEM (n=13) or ESC/PBO (n=13), and completed baseline and 3-month follow-up resting state magnetic resonance imaging scans. DMN maps were estimated using group independent analysis and dual regression; a single DMN component, comprising both anterior and posterior DMN key nodes (precuneus and medial prefrontal cortices), was identified. The 3-month change in DMN connectivity was calculated by subtracting the baseline DMN map from the 3-month DMN map. Multi-block partial least squares correlation analysis was used to evaluate the impact of treatment on DMN connectivity changes and their relationship with symptom improvement (as assessed by the MADRAS) at 3 months (controlling for age and sex). <h3>Results</h3> A significant latent variable was identified, reflecting DMN connectivity related to symptom improvement (p=0.01). Although there were no significant overall group differences in DMN connectivity changes, greater improvement in depressive symptoms was more strongly correlated with DMN connectivity increases in posterior and lateral DMN regions, as well as both increases and decreases in portions of the anterior DMN, in the ESC/MEM group (r=0.97, 95% confidence interval: 0.85-0.98) than in the ESC/PBO group (r=0.36, 95% confidence interval: 0.14-0.71). Figure 1 shows the DMN connectivity changes associated with symptom improvement (Red areas: increased DMN connectivity following treatment was more positively associated with symptom improvement in the ESC/MEM group than in the ESC/PBO group. Blue areas: decreased DMN connectivity following treatment was more positively associated with symptom improvement in the ESC/MEM group than in the ESC/PBO group). <h3>Conclusions</h3> Increased DMN connectivity in posterior and lateral nodes of the DMN following 3 months of treatment with ESC was associated with greater improvement in depression severity as assessed by the MADRS; however, this relationship was further enhanced with the addition of MEM than with placebo. This stronger relationship at 3 months from treatment initiation may be related to greater longer-term clinical and cognitive outcomes with ESC/MEM than with ESC/PBO. The present study adds to the limited literature on the role of the DMN in treatment-related effects in geriatric depression, and supports an improved engagement of brain circuitry beneficial to the amelioration of depressive symptoms with combined ESC/MEM treatment in older adults with depression and subjective memory complaints. <h3>Funding</h3> Sponsored by NIH grants R01MH097892 and AT009198, and National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR001881.

Improving depression and well-being in older adults using selection, optimization, and compensation model: A case series

Background: There is a need to study age-sensitive psychological management for improving the clinical and overall health outcome for elderly adults. Hence, we intended to evaluate the effects of selection, optimization, and compensation (SOC) model, usually studied in nonmental health settings predominantly, in managing depression and well-being of the elderly in a clinical mental health setting in an Indian context. Methods: A pre–postintervention with a 2-month-follow-up approach was adopted. We delivered six sessions over 4–5 months. An independent rater assessed participants using the Beck Depression Inventory-II and World Health Organization's Well-Being Index (WHO-5) at baseline, postintervention, and a 2-month follow-up. Results: There was a clinically significant improvement in depression severity and well-being of participants at the postintervention and 2-month follow-up. Conclusions: SOC-based intervention has potential therapeutic effects in improving depression severity and well-being of elderly individuals in clinical settings. We recommend the current protocol to be studied in a randomized design study with a larger sample size and a longer follow-up period.

Ex vivo glucocorticoid receptor-mediated IL-10 response predicts the course of depression severity

Directly measuring hypothalamic pituitary adrenal (HPA) axis function, an important player in affective disorders, is intensive and invasive. A crucial component of this system, the activity of the glucocorticoid receptor (GR), can be assessed ex vivo instead. Here, we investigated GR sensitivity in patients with major depressive disorder (MDD) to determine its predictive potential. Psychometric data and blood samples were collected from patients experiencing a major depressive episode (MDE, n = 87), healthy control subjects (n = 49), and patients with remitted MDD (n = 31) at baseline and (for patients) after median 20 days of follow-up after treatment as usual. Blood cells were stimulated ex vivo with lipopolysaccharide and the effect was suppressed by increasing dexamethasone (DEX) concentrations. The resultant cytokine secretion profile (for IL-6, IL-10, and TNF-α) was considered indicative of GR activity. Higher baseline scores of the Montgomery–Åsberg Depression Rating Scale (MADRS) were associated with a stronger decrease of logIC IL-6 (indicating an increase of GR sensitivity). Higher baseline logEC IL-10 (indicating a lower GR sensitivity) and a stronger reduction of logEC IL-10 (indicating a stronger increase in GR sensitivity) were associated with a stronger decrease in the MADRS score. Patients with remitted MDD showed higher logIC TNF-α values (indicating lower GR sensitivity) in comparison to patients with a current MDD at baseline and follow-up. Initially low GR sensitivity measured ex vivo in peripheral blood cells that increases over the course of treatment could serve as a predictive marker for stronger improvement in depression severity.

Effects and feasibility of hyperthermic baths in comparison to exercise as add-on treatment to usual care in depression: a randomised, controlled pilot study

BackgroundLimitations of current therapy of depression highlight the need for an immediately available, easily implementable add-on treatment option with high acceptance from patients. Hyperthermic baths (HTB) are a form of balneotherapy with head-out-of-water-immersion in a hot pool or tub at 40 °C for 15–20 min. A prior study suggests that HTB added to usual depression care can have antidepressant effects.MethodSingle-site, open-label randomised controlled 8-week parallel-group pilot study at a university outpatient clinic. 45 medically stable outpatients with moderate depression as determined by the 17-item Hamilton Depression Rating Scale (HAM-D) score ≥ 18 and a score ≥ 2 on item 1 (Depressed Mood) were recruited. They were randomised to twice weekly HTB (n = 22) or a physical exercise program (PEP) of moderate intensity (n = 23). Primary outcome measure was the change in HAM-D total score from baseline (T0) to the 2-week time point (T1). Linear regression analyses, adjusted for baseline values, were performed to estimate intervention effects on an intention-to-treat (ITT) and per-protocol (PP) principle.ResultsForty-five patients (HTB n = 22; PEP n = 23) were analyzed according to ITT (mean age = 48.4 years, SD = 11.3, mean HAM-D score = 21.7, SD = 3.2). Baseline-adjusted mean difference after 2 weeks was 4.3 points in the HAM-D score in favor of HTB (p < 0.001). Compliance with the intervention and follow-up was far better in the HTB group (2 vs 13 dropouts). Per protocol analysis only showed superiority of HTB as a trend (p = 0.068). There were no treatment-related serious adverse events. Main limitation: the number of dropouts in the PEP group (13 of 23) was higher than in other trials investigating exercise in depression. Due to the high number of dropouts the effect in the ITT-analysis may be overestimated.ConclusionsHTB added to usual care may be a fast-acting, safe and easy accessible method leading to clinically relevant improvement in depression severity after 2 weeks; it is also suitable for persons who have problems performing exercise training.Trial registrationGerman Clinical Trials Register (DRKS) with the registration number DRKS00011013 (registration date 2016-09-19) before onset of the study.