Reduction In Depression Severity Research Articles

No benefit from flexible titration above minimum licensed dose in prescribing antidepressants for major depression: systematic review.

In fixed-dose antidepressant trials, the lower range of the licensed dose achieves the optimal balance between efficacy and tolerability. Whether flexible upward titration while side-effects permit provides additional benefits is unknown. We did a systematic review of placebo-controlled randomized trials that examined selective serotonin reuptake inhibitors (SSRIs), venlafaxine or mirtazapine in the acute treatment of major depression. Our primary outcome was response, defined as 50% or greater reduction in depression severity. Secondary outcomes included drop-outs due to adverse effects and drop-outs for any reason. We conducted random-effects meta-analyses to calculate the ratios of odds ratios (RORs) between trials comparing the flexible dose titrating above the minimum licensed dose against placebo and those comparing the fixed minimum licensed dose against placebo. We included 123 published and unpublished randomized controlled trials (29420 participants). There was no evidence supporting efficacy of the flexible dosing over the fixed low dose of SSRIs (ROR 0.96, 95% CI: 0.73 to 1.25), venlafaxine (1.24, 0.96 to 1.60) or mirtazapine (0.77, 0.33 to 1.78). No important differences were noted for tolerability or for any subgroup analyses except the superior efficacy of venlafaxine flexible dosing between 75 and 150mg over the fixed 75mg (1.30, 1.02 to 1.65). There was no evidence to support added value in terms of efficacy, tolerability or acceptability of flexibly titrating up the dosage over the minimum licensed dose of SSRIs or mirtazapine. For venlafaxine, increased efficacy can be expected by flexibly titrating up to 150mg.

Ayahuasca’s Antidepressant Effects Covary with Behavioral Activation as Well as Mindfulness

ABSTRACT Ayahuasca, a plant-based hallucinogen that serves as a spiritual medicine in South America, has improved depression in at least one placebo-controlled clinical trial. Case studies suggest that dramatic behavioral changes often follow the Ayahuasca ceremony, but most explanations of antidepressant effects focus on changes in mindfulness. This study investigated whether both mindfulness and behavioral activation might contribute to these anti-depressant effects. We surveyed individuals (N = 152) about their changes in depressive symptoms, behavioral activation, and mindfulness after an Ayahuasca experience. Mindfulness was strongly associated with reduced depression severity (r = − .670, p < .001), while behavioral activation was moderately linked (r = − .474, p < .001). Changes in depressive symptoms (Center for Epidemiological Sciences Depression Short Form [CES-D-10]) covaried with subscales from the Five Facet Mindfulness Questionnaire [FFMQ] and Experiences Questionnaire [EQ], confirming previous findings (β = −.57, 95% CI −5.70, −3.25), p < .001). In addition, a modification of the Behavioral Activation for Depression Scale-Short Form [BADS-SF] accounted for significant unique variance in the improvements in depression (β = − .16, 95% CI −6.32, −0.08), p < .05). Changes in behavioral activation likely serve as a mechanism underlying Ayahuasca’s antidepressant effects. Future clinical trials could benefit from tracking behavioral activation.

Treating Depression Mindfully in a Day Hospital: a Randomised Controlled Pilot Study

ObjectivesRecent preliminary evidence suggests that mindfulness-based programmes may be beneficial in the treatment of patients suffering from current depression. Due to the heterogeneity of patients with this diagnosis, a specialisation in treatment concepts for subgroups of patients may be beneficial.MethodsThis randomised controlled pilot study investigated the effectiveness of an eight-week mindfulness-based day hospital treatment for patients with current depression and work-related conflicts (MDT-DH) under naturalistic conditions. Eighty-one currently depressed patients with work-related conflicts were randomly assigned to either MDT-DH (including personalised psychopharmacological treatment if necessary) or a waitlist condition including a psychopharmacological consultation (PCC). Outcomes were assessed at post-treatment and at 8-month follow-up. The primary outcome was depression severity (Beck Depression Inventory) at post-treatment. Secondary outcomes were work ability (Work Ability Index) and mindfulness (Kentucky Inventory of Mindfulness Skills).ResultsA multilevel analysis revealed that compared with patients in PCC, patients in the MDT-DH group showed a greater reduction in depression severity, higher work ability and heightened levels of mindfulness after 8 weeks than patients in the PCC group. These improvements were stable during the 8-month follow-up period.ConclusionsFindings of the present pilot study suggest that a treatment concept involving intensive training in mindfulness can be successfully established in a day hospital and leads to clinically meaningful reductions in depression severity and increases in work ability in patients suffering from current depression. The generalisability of the findings may be limited due to small sample size, selective patient group and study design.

Are early increases in physical activity a behavioral marker for successful antidepressant treatment?

BackgroundThe aim of this study was to examine whether changes in physical activity predicted reductions in depression during the 8 weeks of antidepressant treatment with vortioxetine. MethodsOne hundred individuals were recruited for the (THINC-it ®)-sensitivity to change study. Self-reported moderate-to-vigorous physical activity (MVPA) and depression severity were assessed at baseline, week 4 and week 8. Linear mixed model analyses were performed to examine whether increases in MVPA were associated with reduction in depression severity over the course of treatment and hierarchical logistic regression analyses were performed to assess whether treatment response (responders vs. non-responders) at week 8 was predicted by early change in physical activity (MVPA at week 4), after controlling for individuals’ demographics (sex, age, race, education level, BMI) and baseline MVPA and depression severity. ResultsAfter controlling for individuals’ demographics, a significant increase in MVPA predicted reduction in depression severity, β = -2.06, 95% CI -3.18, -0.94, p <0.001. Individuals with more physical activity at week 4 relative to baseline had higher odds of treatment response at endpoint, OR 1.97, 95% CI 1.11 – 3.48, p <0.05. Twenty-one percent of total variance of depression severity was explained by change in MVPA. ConclusionsThe study suggests that early increases in physical activity may be a behavioral marker of antidepressant treatment response. The inclusion of physical activity measures in future clinical treatment trials of depression is recommended to explore whether changes in physical activity mediate or moderate reductions in depression severity associated with the primary treatment.

Biomarkers for response in major depression: comparing paroxetine and venlafaxine from two randomised placebo-controlled clinical studies

The identification of biomarkers of response might speed drug development and set the premises to assist clinical practice in psychiatry. In this work, we evaluated a panel of peripheral biomarkers (including IL-6, IL-10, TNF-α, TNFRII, BDNF, CRP, MMP9 and PAI1) in depressed patients receiving paroxetine, venlafaxine, or placebo. Samples were obtained from two randomised placebo-controlled studies evaluating the efficacy and tolerability of a novel drug candidate, using either paroxetine or venlafaxine as active comparators. In both studies, the biomarker candidates were analysed in plasma collected at randomization and after 10 weeks of treatment with either placebo or active comparator (for a total of 106 and 108 subjects in the paroxetine and venlafaxine study, respectively). Data were obtained by multiplexing sandwich-ELISA system. Data were subjected to statistical analysis to assess their correlation with baseline severity and with response outcome. Increases in biomarker levels were correlated with reduction in depression severity for TNF-α, IL-6 IL-10 and CRP. Response to paroxetine treatment correlated with baseline IL-10, IL-6 and TNF-α levels, with the strongest signal being observed in males. In the venlafaxine study, a correlation was observed only between CRP level at randomisation and response, suggesting differences between the two active treatments and the two studies. Our investigations suggest that a combination of pro- and anti-inflammatory cytokines may predict response outcome in patients treated with paroxetine. The potential for IL-10, IL-6 and TNF-α as response biomarkers for a wider range of antidepressants warrants further investigations in clinical trials with other monoamine reuptake inhibitors.

Managing Depression with Bupleurum chinense Herbal Formula: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: Bupleurum chinense (BC; Radix Bupleuri) formulae are widely used in herbal medicine clinical practice for major depressive disorder (MDD). This study provides an up-to-date and comprehensive systematic review and meta-analysis of BC formula for MDD. Design: Randomized controlled trials were retrieved from English and Chinese databases, from their inceptions to March 2019. Included studies compared BC formula alone or as integrative medicine to selective serotonin reuptake inhibitor (SSRI) antidepressants. Studies included adults 18-65 years of age. People with other types of depression or physical comorbidities, such as poststroke depression, bipolar, and other mental or physical disorders, were excluded. Meta-analysis was performed using STATA software. Grading of Recommendations Assessment, Development, and Evaluation was also conducted to assess the quality of evidence. Results: Thirty studies compared BC formula to antidepressants and 25 studies compared BC formula plus antidepressants to antidepressants alone. BC formula was more effective than antidepressants at improving depression severity measured on the Hamilton Rating Scale for Depression (HRSD) (standardized mean difference [SMD] -0.35, 95% confidence interval [CI] -0.52 to -0.18, I2 = 81.2%). Integrative use of BC formula plus SSRIs was also superior to SSRIs alone at improving HRSD scores (SMD -1.03, 95% CI -1.43 to -0.62, I2 = 94.2%). However, heterogeneity of the included studies was high and quality was low. The total number and severity of adverse events in the BC formula groups were less than that in the antidepressant groups. Conclusions: BC formula alone or given as integrative medicine with antidepressants reduced depression severity. However, the evidence is low quality and at risk of bias. Well-designed studies are needed to validate the results we identified in this review.

Evaluating the role of levels of exposure to a task shared depression counselling intervention led by behavioural health counsellors: outcome and process evaluation

BackgroundIn the context of a large treatment gap for common mental disorders (CMDs) and shortage of mental health specialists in low- and middle-income countries, there is increasing evidence of the effectiveness of task sharing of counselling interventions to increase access to mental health care for CMDs at primary health care level. This study evaluated the relationship between levels of exposure to a task-shared counselling intervention and psychosocial outcomes (depression, functional disability, internalised stigma and social support) in chronic care service users with comorbid depression in South Africa guided by the Medical Research Council process evaluation framework. Implementation and participant-level factors that promote greater exposure were also investigated.MethodThe study design was a cohort study comprising of 173 participants referred by primary health care nurses for the task-shared counselling intervention. The study site comprised four primary health care facilities in a sub-district of the Dr. Kenneth Kaunda district in the North West Province of South Africa. The participants were assessed for psychosocial outcomes at three time points: baseline, 3 months and at 12 months. The number of counselling sessions each participant was exposed to was collected for each participant. Linear regression models were used to test the influence of counselling exposure on each of the psychosocial variables between baseline and endline. In-depth qualitative interviews were conducted on 29 randomly selected participants, stratified according to exposure to counselling sessions, and analysed using framework analysis.FindingsFindings from the cohort study indicated a significant reduction in depression severity at 12 months. Internalised stigma and functional disability improved from baseline to endline. Participants receiving 5–8 sessions have the greatest reduction in PHQ9 scores from baseline to endline (β = − 2.46, 95% CI − 5.06 to 0.15) compared to those with 0 sessions (β = − 0.51, 95% CI − 3.62 to 2.60, p = 0.064). The WHODAS scores decreased significantly more from baseline to endline among those who received 5–8 sessions (β = − 10.73, 95% CI − 19.86 to 1.59) compared to those with 0 sessions (β = 2.25, 95% CI − 8.65 to 13.14, p = 0.021). No significant differences as a function of levels of counselling exposure from baseline to endline was observed for OSS-3 scores. An improvement in ISMI scores from 1–4 sessions to 5–8 sessions was found (β = − 4.05, 95% CI − 7.30 to − 0.80, p = 0.015). The qualitative process evaluation indicated that the service was acceptable and accessible; but that session attendance was hindered by women’s’ caregiving burden, poor counsellor attributes and poor referral processes.ConclusionExposure to a greater number of sessions (5–8 sessions) was found to optimize functional ability, reduce stigma, and potentially reduce depression symptoms. In order to enhance session attendance, lay counsellor delivered psychosocial interventions need to pay attention to (i) counsellor selection criteria, particularly person-centred care qualities; and (ii) strengthening referral processes in contexts where mental health literacy is low.

Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systematic review and dose-response meta-analysis

SummaryBackgroundDepression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological management of depression. Optimising their use is crucial in reducing the burden of depression; however, debate about their dose dependency and their optimal target dose is ongoing. We have aimed to summarise the currently available best evidence to inform this clinical question.MethodsWe did a systematic review and dose-response meta-analysis of double-blind, randomised controlled trials that examined fixed doses of five selective serotonin reuptake inhibitors (SSRIs; citalopram, escitalopram, fluoxetine, paroxetine, and sertraline), venlafaxine, or mirtazapine in the acute treatment of adults (aged 18 years or older) with major depression, identified from the Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS, MEDLINE, PsycINFO, AMED, PSYNDEX, websites of drug licensing agencies and pharmaceutical companies, and trial registries. We imposed no language restrictions, and the search was updated until Jan 8, 2016. Doses of SSRIs were converted to fluoxetine equivalents. Trials of antidepressants for patients with depression and a serious concomitant physical illness were excluded. The main outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reasons), all after a median of 8 weeks of treatment (range 4–12 weeks). We used a random-effects, dose-response meta-analysis model with flexible splines for SSRIs, venlafaxine, and mirtazapine.Findings28 554 records were identified through our search (24 524 published and 4030 unpublished records). 561 published and 121 unpublished full-text records were assessed for eligibility, and 77 studies were included (19 364 participants; mean age 42·5 years, SD 11·0; 7156 [60·9%] of 11 749 reported were women). For SSRIs (99 treatment groups), the dose-efficacy curve showed a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg fluoxetine equivalents. Dropouts due to adverse effects increased steeply through the examined range. The relationship between the dose and dropouts for any reason indicated optimal acceptability for the SSRIs in the lower licensed range between 20 mg and 40 mg fluoxetine equivalents. Venlafaxine (16 treatment groups) had an initially increasing dose-efficacy relationship up to around 75–150 mg, followed by a more modest increase, whereas for mirtazapine (11 treatment groups) efficacy increased up to a dose of about 30 mg and then decreased. Both venlafaxine and mirtazapine showed optimal acceptability in the lower range of their licensed dose. These results were robust to several sensitivity analyses.InterpretationFor the most commonly used second-generation antidepressants, the lower range of the licensed dose achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression.FundingJapan Society for the Promotion of Science, Swiss National Science Foundation, and National Institute for Health Research.

Antidepressant outcomes of high-frequency repetitive transcranial magnetic stimulation (rTMS) with F8-coil and deep transcranial magnetic stimulation (DTMS) with H1-coil in major depression: a systematic review and meta-analysis

BackgroundThe current study aims to systematically assess and compare the antidepressant outcomes of repetitive transcranial magnetic stimulation (rTMS) with the figure-of-eight (F8)-coil and deep transcranial magnetic stimulation (DTMS) with the H1-coil in studies matched on stimulation frequency in unipolar major depressive disorder (MDD).MethodsElectronic search of Medline and PsycInfo identified 19 studies with stimulation frequency of 18–20 Hz using F8-coil (k = 8 randomised sham-controlled trials, RCTs, k = 3 open-label; n = 168 patients) or H1-coil (k = 1 RCT, k = 7 open-label; n = 200). Depression severity (the primary outcome) and response/remission rates (the secondary outcomes) were assessed at session 10.ResultsEffects pooled with random-effects meta-analysis showed a large reduction in depression severity, 29% response, and 15% remission rates after 10 sessions of active stimulation with either coil relative to baseline. Reduction in depression severity was greater in studies with younger patients using either coil. The comparison between coils showed a larger reduction in depression severity in H1-coil vs. F8-coil studies (independent of the study design or the concurrent pharmacotherapy) and a trend towards higher remission rates in F8-coil vs. H1-coils studies. These effects are based on a low volume of studies, are not controlled for placebo, and may not be clinically-relevant. The stimulation protocols differed systematically because stimulation was more focal but less intense (80–110% of the resting motor threshold, MT) in the F8-coil studies and less focal but more intense (120% MT) in the H1-coil studies. Two seizures occurred in the H1-coil studies relative to none in the F8-coil studies.ConclusionWhen matched on frequency, the higher-intensity and less focal stimulation with the H1-coil reduces depression more than the lower-intensity and more focal stimulation with the F8-coil. Head-to-head trials should compare the antidepressant outcomes of F8-coil and H1-coil to identify the most optimal stimulation protocols for acute and longer-lasting efficacy.

Efficacy of repetitive transcranial magnetic stimulation using a figure-8-coil or an H1-Coil in treatment of major depressive disorder; A randomized clinical trial

Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment option for major depressive disorder (MDD). However, comparisons of efficacy between the two FDA-approved protocols of rTMS modalities are lacking. The aim of this industry-independent, randomized-controlled, single-blind trial was to evaluate clinical outcome of the two FDA-approved rTMS protocols delivered by H1-coil and the figure-8-coil, in MDD patients. A total of 228 MDD patients were randomized to 20 sessions of H1-coil or 8-coil as an adjunct to standard-of-care pharmacotherapy, or standard-of-care pharmacotherapy alone. Baseline MDD symptom severity was almost the same in the three groups. Hamilton depression rating scale (HAM-D17) mean score was 17 (5.3) in H1-coil, 17 (5.4) in 8-coil, and 19 (6.1) in control group. The primary outcome was the proportion of patients achieving remission defined as HAM-D17 score ≤7 at end-of-treatment at week-4. In the intention-to-treat analysis odds ratio for remission was 1.74 (CI95% 0.79–3.83) in H1-coil compared to the 8-coil group. The difference between two rTMS protocols was not significant. Remission rate was significantly greater in both HF-rTMS groups compared to the control: 60% (CI95% 48–71%), 43% (CI95% 31–55%) and 11% (CI95% 5–20%) respectively. The response was significantly better in H1-coil, than in 8-coil group OR = 2.33; CI95% 1.04–5.21 (P = 0.040). The HAM-D17 was lowered by 59% in the H1-coil, 41% in the 8-coil (P = 0.048), and 17% in the control group (P < 0.001 vs H1-coil; P = 0.003 vs 8-coil). Safety, tolerability, and the changes in quality of life were comparable. We confirmed the safety and efficacy of both FDA-approved protocols as adjunctive treatments of MDD. Better response rate and greater reduction of depression severity were observed in the H1-coil group, but without a significant difference in the remission rate between the two rTMS modalities. Clinical trials registrationClinicaltrials.govNCT02917499

RHYTHMIC TRANSKRANIAL MAGNETIC STIMULATION IN TREATMENT OF PATIENTS WITH DEPRESSION

23 patients with clinically proven diagnosis of depression were treated with the help of rTMS. The signs of depression were assessed according to the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Depression Scale. The low-frequency (1 Hz) rTMS was conducted on “Neuro-MS/T” with the intensity of 80% from the threshold of motor response to the TMS of the right dorsolateral prefrontal cortex, number of trains – 60, duration – 23 minutes. &#x0D; After 10 sessions of rTMS, the patients noted the improvement of sleep (15), mood improvement (19), a calmer reaction to stressful situations (14). A reduction of depression severity according to assessment scales was also registered (р &lt; 0,05). &#x0D; The therapeutic rTMS method and the chosen protocol of stimulation proved to be effective in treatment of depression and can be used in medical practice under the control of psychotherapist. &#x0D; 23 patients with clinically proven diagnosis of depression were treated with the help of rTMS. The signs of depression were assessed according to the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Depression Scale. The low-frequency (1 Hz) rTMS was conducted on “Neuro-MS/T” with the intensity of 80% from the threshold of motor response to the TMS of the right dorsolateral prefrontal cortex, number of trains – 60, duration – 23 minutes. &#x0D; After 10 sessions of rTMS, the patients noted the improvement of sleep (15), mood improvement (19), a calmer reaction to stressful situations (14). A reduction of depression severity according to assessment scales was also registered (р &lt; 0,05). &#x0D; The therapeutic rTMS method and the chosen protocol of stimulation proved to be effective in treatment of depression and can be used in medical practice under the control of psychotherapist. &#x0D; 23 patients with clinically proven diagnosis of depression were treated with the help of rTMS. The signs of depression were assessed according to the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Depression Scale. The low-frequency (1 Hz) rTMS was conducted on “Neuro-MS/T” with the intensity of 80% from the threshold of motor response to the TMS of the right dorsolateral prefrontal cortex, number of trains – 60, duration – 23 minutes. &#x0D; After 10 sessions of rTMS, the patients noted the improvement of sleep (15), mood improvement (19), a calmer reaction to stressful situations (14). A reduction of depression severity according to assessment scales was also registered (р &lt; 0,05). &#x0D; The therapeutic rTMS method and the chosen protocol of stimulation proved to be effective in treatment of depression and can be used in medical practice under the control of psychotherapist. &#x0D; 23 patients with clinically proven diagnosis of depression were treated with the help of rTMS. The signs of depression were assessed according to the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Depression Scale. The low-frequency (1 Hz) rTMS was conducted on “Neuro-MS/T” with the intensity of 80% from the threshold of motor response to the TMS of the right dorsolateral prefrontal cortex, number of trains – 60, duration – 23 minutes. &#x0D; After 10 sessions of rTMS, the patients noted the improvement of sleep (15), mood improvement (19), a calmer reaction to stressful situations (14). A reduction of depression severity according to assessment scales was also registered (р &lt; 0,05). &#x0D; The therapeutic rTMS method and the chosen protocol of stimulation proved to be effective in treatment of depression and can be used in medical practice under the control of psychotherapist. &#x0D; 23 patients with clinically proven diagnosis of depression were treated with the help of rTMS. The signs of depression were assessed according to the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Depression Scale. The low-frequency (1 Hz) rTMS was conducted on “Neuro-MS/T” with the intensity of 80% from the threshold of motor response to the TMS of the right dorsolateral prefrontal cortex, number of trains – 60, duration – 23 minutes. &#x0D; After 10 sessions of rTMS, the patients noted the improvement of sleep (15), mood improvement (19), a calmer reaction to stressful situations (14). A reduction of depression severity according to assessment scales was also registered (р &lt; 0,05). &#x0D; The therapeutic rTMS method and the chosen protocol of stimulation proved to be effective in treatment of depression and can be used in medical practice under the control of psychotherapist.

RHYTHMIC TRANSKRANIAL MAGNETIC STIMULATION IN TREATMENT OF PATIENTS WITH DEPRESSION

23 patients with clinically proven diagnosis of depression were treated with the help of rTMS. The signs of depression were assessed according to the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Depression Scale. The low-frequency (1 Hz) rTMS was conducted on “Neuro-MS/T” with the intensity of 80% from the threshold of motor response to the TMS of the right dorsolateral prefrontal cortex, number of trains – 60, duration – 23 minutes. &#x0D; After 10 sessions of rTMS, the patients noted the improvement of sleep (15), mood improvement (19), a calmer reaction to stressful situations (14). A reduction of depression severity according to assessment scales was also registered (р &lt; 0,05). &#x0D; The therapeutic rTMS method and the chosen protocol of stimulation proved to be effective in treatment of depression and can be used in medical practice under the control of psychotherapist. &#x0D; 23 patients with clinically proven diagnosis of depression were treated with the help of rTMS. The signs of depression were assessed according to the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Depression Scale. The low-frequency (1 Hz) rTMS was conducted on “Neuro-MS/T” with the intensity of 80% from the threshold of motor response to the TMS of the right dorsolateral prefrontal cortex, number of trains – 60, duration – 23 minutes. &#x0D; After 10 sessions of rTMS, the patients noted the improvement of sleep (15), mood improvement (19), a calmer reaction to stressful situations (14). A reduction of depression severity according to assessment scales was also registered (р &lt; 0,05). &#x0D; The therapeutic rTMS method and the chosen protocol of stimulation proved to be effective in treatment of depression and can be used in medical practice under the control of psychotherapist. &#x0D; 23 patients with clinically proven diagnosis of depression were treated with the help of rTMS. The signs of depression were assessed according to the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Depression Scale. The low-frequency (1 Hz) rTMS was conducted on “Neuro-MS/T” with the intensity of 80% from the threshold of motor response to the TMS of the right dorsolateral prefrontal cortex, number of trains – 60, duration – 23 minutes. &#x0D; After 10 sessions of rTMS, the patients noted the improvement of sleep (15), mood improvement (19), a calmer reaction to stressful situations (14). A reduction of depression severity according to assessment scales was also registered (р &lt; 0,05). &#x0D; The therapeutic rTMS method and the chosen protocol of stimulation proved to be effective in treatment of depression and can be used in medical practice under the control of psychotherapist. &#x0D; 23 patients with clinically proven diagnosis of depression were treated with the help of rTMS. The signs of depression were assessed according to the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Depression Scale. The low-frequency (1 Hz) rTMS was conducted on “Neuro-MS/T” with the intensity of 80% from the threshold of motor response to the TMS of the right dorsolateral prefrontal cortex, number of trains – 60, duration – 23 minutes. &#x0D; After 10 sessions of rTMS, the patients noted the improvement of sleep (15), mood improvement (19), a calmer reaction to stressful situations (14). A reduction of depression severity according to assessment scales was also registered (р &lt; 0,05). &#x0D; The therapeutic rTMS method and the chosen protocol of stimulation proved to be effective in treatment of depression and can be used in medical practice under the control of psychotherapist. &#x0D; 23 patients with clinically proven diagnosis of depression were treated with the help of rTMS. The signs of depression were assessed according to the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Depression Scale. The low-frequency (1 Hz) rTMS was conducted on “Neuro-MS/T” with the intensity of 80% from the threshold of motor response to the TMS of the right dorsolateral prefrontal cortex, number of trains – 60, duration – 23 minutes. &#x0D; After 10 sessions of rTMS, the patients noted the improvement of sleep (15), mood improvement (19), a calmer reaction to stressful situations (14). A reduction of depression severity according to assessment scales was also registered (р &lt; 0,05). &#x0D; The therapeutic rTMS method and the chosen protocol of stimulation proved to be effective in treatment of depression and can be used in medical practice under the control of psychotherapist.

How to determine whether conceptual endophenotypes can improve clinical outcomes in patients suffering from major depression: An exploratory approach

Depression is a complex mental health disorder, resulting in a high degree of disability. Since symptom constellation, course, and outcome are heterogeneous in these patients, current research initiatives are striving to establish stratified diagnostic and treatment approaches. In the past two decades, Dirk Hellhammer and his team introduced Neuropattern, a new diagnostic concept, which is based on conceptual endophenotypes of the stress response network. We explore how to use this concept in clinical practice in order to ultimately determine whether it brings any value over standard care. In view of the novelty of the concept and the difficulties dealing with such a concept at a practical level, it was necessary to initiate an exploratory study to determine key factors for planning future clinical trials.We report results and knowledge gained from an exploratory single-site study investigating the use and potential benefits of Neuropattern in standard care. Inpatients (ICD-10 diagnosis F32, F33; Nö=ö178) were allocated to either treatment as usual (standard group, SG) or a novel Neuropattern oriented exploratory treatment (intervention group, IG). Symptom severity was assessed with psychometric tests at admission to hospital, during the first six weeks, and upon discharge from the hospital. In addition, direct and indirect costs were assessed for the 3-month-intervals prior to and after the hospital stay.Compared to the SG, depression scores of patients in the IG showed a faster decline once psychotherapeutic and pharmacological treatment were based on an individualized explanatory model. The patients in the IG with an F33 diagnosis showed a more pronounced reduction of depression severity during the stay in the hospital and a stronger and quicker reduction of general symptom severity. Comparing the average depression scores at the start of the study and after six weeks, symptom severity was reduced in all Neuropattern groups.Some limitations of the study have to be mentioned: The study was not blinded, was single-site, included highly depressed inpatients only, and was conducted for no longer than 8 months. The results highlight some important issues regarding taking the Neuropattern approach to the bedside and researching its efficacy and effectiveness to support personalized treatments in clinical care.

Exploratory analyses of effect modifiers in the antidepressant treatment of major depression: Individual-participant data meta-analysis of 2803 participants in seven placebo-controlled randomized trials

BackgroundIt is clinically important to know who are likely to respond more or less to antidepressants. However, meaningful effect modifiers (variables associated with differential response depending on the treatment) are yet to be identified. MethodsWe conducted individual participant data (IPD) meta-analysis and meta-regression to explore effect modifiers in placebo-controlled antidepressant trials conducted so far in Japan. ResultsWe obtained access to IPD from seven placebo-controlled trials comparing bupropion, duloxetine, escitalopram, mirtazapine, paroxetine or venlafaxine with placebo in the acute phase treatment of major depression (total n = 2803). The higher the guilt subscale score of the baseline Hamilton Rating Scale for Depression (HRSD), the greater the difference in reduction in depression severity between the antidepressants and placebo at week 6, while the older the current age or the age at onset, the smaller the difference. At week 8, the guilt subscale score of HRSD and presence of suicidal ideation at baseline predicted greater, and the anhedonia subscale and insomnia subscale scores of HRSD and early response at week 2 predicted smaller, difference in reduction. LimitationsDifferent studies measured different sets of baseline variables and we were able to analyze only a limited set of candidate variables for effect modification. ConclusionAge, age at onset, several HRSD subscales including guilt, anhedonia and insomnia, presence of suicidal ideation at baseline and early response are potential effect modifiers for response to antidepressants in the acute phase antidepressant treatment of major depression. Future trials need to measure these and additional variables in concerted efforts to enable matching of treatments with individual characteristics in depression.

Effectiveness of Shared Decision-Making for Elderly Depressed Minority Primary Care Patients

The authors assessed the impact of a shared decision-making (SDM) intervention among elderly depressed minority primary care patients not currently receiving treatment. A total of 202 English and Spanish-speaking primary care participants aged 65 and older who scored positive on the Patient Health Questionnaire-9 (≥10) were randomized at the physician level to receive a brief SDM intervention or usual care (UC). Primary analyses focused on patient adherence to either psychotherapy or antidepressant medication, and reduction in depression severity (Hamilton Depression Rating Scale) over 12 weeks. Patients randomized to physicians in the SDM condition were significantly more likely than patients of physicians randomized to UC to receive a mental health evaluation or initiate some form of treatment (39% versus 21%), and to adhere to psychotherapy visits over 12 weeks. There were no differences between groups in adherence to antidepressant medication or in reduction of depressive symptoms. Among untreated elderly depressed minority patients from an inner-city municipal hospital, a brief SDM intervention was associated with greater initiation and adherence to psychotherapy. However, low treatment adherence rates across both groups and the intervention's lack of impact on clinical outcomes highlight the need to provide focused and accessible mental health services to patients choosing active treatments.

An Uncontrolled Open Trial of a Brief Behavioural Activation Treatment for Depression in Patients with Chronic Spontaneous Urticaria

AbstractChronic spontaneous urticaria (CSU) has been associated with depression and can have an impact on quality of life. Therefore, researchers have suggested the potential utility of psychological interventions for targeting depression among CSU patients. Psychological interventions that may hold the most promise are those that are brief and easily transportable, such as brief behavioural activation treatment for depression. We report results of a preliminary investigation of an uncontrolled open trial of a one-session behavioural activation treatment for depression designed for patients with CSU (BATD-CSU) at a university-based allergy and immunology clinic. Participants were 11 females with chronic, poorly controlled urticaria and symptoms of depression. Following the completion of pretreatment questionnaires, participants were administered BATD-CSU primarily by non-mental health professionals trained and supervised in its delivery. One month post-BATD-CSU, participants completed follow-up questionnaires. Participants exhibited significant reductions in depression severity, avoidance/rumination, and work/school impairment. BATD-CSU was also associated with improvements in urticaria control one month post-treatment. Moreover, five of nine patients reported reliable and clinically significant improvement on at least one outcome. Results demonstrate that BATD-CSU may have benefits for CSU patients even when consisting of one session and delivered by professionals with limited background in psychological interventions, thus speaking to its feasibility and transportability.

A novel approach for assessing neuromodulation using phase-locked information measured with TMS-EEG

Neuromodulation therapies such as electroconvulsive therapy (ECT) are used to treat several neuropsychiatric disorders, including major depressive disorder (MDD). Recent work has highlighted the use of combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) to evaluate the therapeutic effects of neuromodulation; particularly, the phase locking factor (PLF) and phase locking value (PLV) can reportedly assess neuromodulation-induced functional changes in cortical networks. To examine changes in TMS-induced PLV and PLF before and after ECT, and their relationship with depression severity in patients with MDD, TMS-EEG and the Montgomery–Åsberg Depression Rating Scale (MADRS; depression severity) were implemented before and after ECT in 10 patients with MDD. Single-pulse TMS was applied to the visual and motor areas to induce phase propagation in the visuo-motor network at rest. Functional changes were assessed using PLF and PLV data. Pre-ECT TMS-induced alpha band (9–12 Hz) PLV was negatively correlated with depression severity, and increments of post-ECT from pre-ECT TMS-induced alpha band PLV were positively correlated with the reduction in depression severity. Moreover, we found a negative correlation between pre-ECT TMS-induced PLF at TMS-destination and depression severity. Finally, differences in post-ECT TMS-induced PLF peak latencies between visual and motor areas were positively correlated with depression severity. TMS-EEG-based PLV and PLF may be used to assess the therapeutic effects of neuromodulation and depressive states, respectively. Furthermore, our results provide new insights about the neural mechanisms of ECT and depression.

The Effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) in Real-World Healthcare Services

Depression is common with a high risk of relapse/recurrence. There is evidence from multiple randomised controlled trials (RCTs) demonstrating the efficacy of mindfulness-based cognitive therapy (MBCT) for the prevention of depressive relapse/recurrence, and it is included in several national clinical guidelines for this purpose. However, little is known about whether MBCT is being delivered safely and effectively in real-world healthcare settings. In the present study, five mental health services from a range of regions in the UK contributed data (n = 1554) to examine the impact of MBCT on depression outcomes. Less than half the sample (n = 726, 47%) entered with Patient Health Questionnaire (PHQ-9) scores in the non-depressed range, the group for whom MBCT was originally intended. Of this group, 96% sustained their recovery (remained in the non-depressed range) across the treatment period. There was also a significant reduction in residual symptoms, consistent with a reduced risk of depressive relapse. The rest of the sample (n = 828, 53%) entered treatment with PHQ-9 scores in the depressed range. For this group, 45% recovered (PHQ-9 score entered the non-depressed range), and overall, there was a significant reduction in depression severity from pre-treatment to post-treatment. For both subgroups, the rate of reliable deterioration (3%) was comparable to other psychotherapeutic interventions delivered in similar settings. We conclude that MBCT is being delivered effectively and safely in routine clinical settings, although its use has broadened from its original target population to include people experiencing current depression. Implications for implementation are discussed.

Engagement in Socially and Interpersonally Rewarding Activities as a Predictor of Outcome in “Engage” Behavioral Activation Therapy for Late-Life Depression

Loneliness and social isolation are associated with depressive symptoms, cognitive and physical disabilities, and increased risk of mortality among older adults. Socially rewarding activities reduce loneliness, and neurobiological evidence suggests that these activities may activate neural reward systems in older adults to a greater extent than other rewarding experiences. The current study was designed to investigate whether engagement in social and interpersonal activities (i.e., exposure to social rewards) predicts subsequent increase in behavioral activation and reduction in depressive symptoms in reward exposure treatment for late-life depression. Forty-eight older adults without cognitive impairment and with major depression received nine sessions of "Engage" psychotherapy. Behavioral activation and depression severity were assessed by trained raters at baseline and weeks 6 and 9. Patients' weekly behavioral plans were categorized into three groups: 1) solitary activities; 2) social-group activities (attending a social gathering or a social setting such as church or a senior center); and 3) interpersonal-individual activities (engaging in an interpersonal interaction with a specific friend or family member). Mixed-effects models showed reduction in depression severity and increase in behavioral activation over time. In linear regression models, a higher percentage of interpersonal-individual activities (but not solitary or social-group activities) predicted subsequent increase in behavioral activation and improvement of depression. These findings highlight the importance of understanding the effects of engagement in specific types of rewarding activities in behavioral activation treatments for late-life depression. Exposure to socially rewarding interpersonal interactions could contribute to the efficacy of psychotherapy for late-life depression.

Examining the impacts of 12 weeks of low to moderate-intensity aerobic exercise on depression status in patients with systolic congestive heart failure - A randomized controlled study

OBJECTIVES:Psychiatric depression disorder is common in patients with systolic congestive heart failure (HF), and both conditions share underlying pathophysiological mechanisms. The incidence rate of depression disorder has clearly increased with the increase in HF manifestations in recent decades. Depression disorder is considered an independent predisposing factor for hospitalization, disturbed functional performance, and high rates of morbidity and mortality in HF patients. This randomized controlled study was designed to examine the impacts of low- to moderate-intensity aerobic exercise training on depression status in patients with systolic congestive HF.METHODS:A total of 46 systolic congestive HF patients with depression (40-60 years of age) were randomized to receive twelve weeks of mild- to moderate-intensity aerobic exercise plus standard medical treatment (exercise group) or standard medical treatment without any exercise intervention (control group). Depression status was examined using the validated Patient Health Questionnaire-9 (PHQ9) pre- and post-intervention at the end of the study program.RESULTS:No significant differences were observed between the exercise and control groups in demographic data or clinical characteristics (p>0.05). Both study groups showed a significant reduction in depression status at the end of the 12-week intervention (p<0.05). The comparison between the mean values of the depression scores showed significant differences between the two groups after 6 and 12 weeks of the intervention, indicating a greater reduction in depression scores in the exercise group than in the control group (p<0.05).CONCLUSIONS:Twelve weeks of a low- to moderate-intensity aerobic exercise program was safe and effective for reducing depression severity in patients with systolic congestive HF. Low- to moderate-intensity aerobic training should be recommended for cardiac patients, particularly those with HF-related depression.