Montgomery-Asberg Depression Rating Scale Total Score Research Articles

Psychometric properties of the Clinical Assessment Interview for Negative Symptoms (CAINS) in patients with depression and its relationship to affective symptoms

BackgroundThere is a conceptual overlap between negative and depressive symptoms, requiring further exploration to advance the understanding of negative symptoms. The aim of this study was to examine psychometric properties of the Clinical Assessment Interview for Negative Symptoms (CAINS) in patients with depression, and to explore the relationship between the negative and affective symptoms domains.MethodsFifty-one patients with a depressive episode were included and interviewed with the CAINS and the Brief Psychiatric Rating Scale—Expanded (BPRS-E). Self-reported depressive symptoms were collected with the Montgomery-Asberg Depression Rating Scale (MADRS-S). Inter-rater agreement, internal consistency and validity measures were examined, as were correlations between negative and affective symptoms.ResultsThe intraclass correlation for the CAINS motivation and pleasure subscale (CAINS-MAP) was 0.98 (95% CI 0.96–0.99) and that for the expressional subscale (CAINS-EXP) was 0.81 (95% CI 0.67–0.89). Cronbach’s alpha was 0.71 (95% CI 0.57–0.82) for the CAINS-MAP and 0.86 (95% CI 0.79–0.92) for the CAINS-EXP. The correlation with the negative symptoms subscale of the BPRS-E was 0.35 (p = 0.011, blinded/different raters) or 0.55 (p < 0.001, not blinded/same rater). The CAINS-MAP correlated with the affective symptoms subscale of the BPRS-E (r = 0.39, p = 0.005) and the MADRS-S total score (r = 0.50, p < 0.001), but not with anxiety symptoms.ConclusionsNegative symptoms in depression can be assessed with the CAINS with good inter-rater agreement and acceptable internal consistency and validity. There are associations between negative and depressive symptoms that call for further exploration.

Cognitive Function Mediates the Anti-suicide Effect of Repeated Intravenous Ketamine in Adult Patients With Suicidal Ideation.

ObjectivePrior research has shown that ketamine has anti-suicide effects. Additional evidence also suggests that ketamine may offer pro-cognitive effects. Herein, we propose that the anti-suicide effects of ketamine are partially mediated via pro-cognitive effects. We aimed to determine whether improvement in cognitive function mediated change in suicidal ideation was associated with ketamine treatment.MethodsUnipolar or bipolar depressive patients (n = 86) with suicidal ideation received six infusions of ketamine (0.5 mg/kg) over 2 weeks. The current severity of suicidal ideation and depression symptoms were assessed with the Beck Scale for Suicide Ideation (SSI) and the Montgomery–Asberg Depression Rating Scale (MADRS), respectively, at baseline, days 13 and 26. Cognitive domains, including processing speed, working memory, visual learning, and verbal learning were measured with the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery at the same time points.ResultsMediation analysis showed a significant total effect of ketamine treatment on SSI score (coef = –1.853, 95%CI [–2.2, –1.5]). The direct and total indirect (MADRS total score and any of cognitive domains) effects of ketamine on suicidal ideation both were statistically significant (direct: coef = –1.064 to –1.352; total indirect: coef = –0.501 to –0.788). MADRS total score and processing speed (but not other cognitive domains) were significant partial mediators of the association between ketamine treatment and improvements in suicidal ideation.ConclusionDepressive symptoms severity and processing speed performance partially mediated improvements in suicidal ideation after repeated ketamine infusions in persons with unipolar or bipolar depressive disorder.

Reliability and Validity of the Quick Inventory of Depressive Symptomatology-Self-Report Scale in Older Adults With Depressive Symptoms.

Background: Depressive symptoms are common in older adults. Developing rapid self-report tools is essential to measure the presence and severity of depressive symptoms in older adults. This study evaluated the psychometric properties of the Quick Inventory of Depressive Symptomatology—Self-Report (QIDS-SR) scale for use in depressed older adults.Methods: A total of 238 depressed older adults were included in the study. The Montgomery–Asberg Depression Rating Scale (MADRS) and the QIDS-SR were administered to assess the severity of depressive symptoms. Cronbach's alpha coefficient, Spearman rank correlations, and principal component analysis were performed to estimate the internal consistency, convergent validity, and factorial structure of the QIDS-SR, respectively.Results: The Cronbach's alpha for the QIDS-SR was acceptable (α = 0.64). Item–total correlation analyses showed that the items of concentration/decision-making, involvement, energy level, and agitation/retardation had high correlation with the QIDS-SR total score (all correlation coefficients ≥0.60). The QIDS-SR total score was significantly correlated with the MADRS total score (r = 0.53, p < 0.001), demonstrating acceptable convergent validity. Factor analysis revealed the unidimensional structure of the QIDS-SR.Conclusions: The QIDS-SR appears to be a reliable and valid self-report scale for estimating the severity of depressive symptoms in depressed older adults.

A Randomized, Double-blind, Placebo-controlled Proof-of-Concept Trial to Evaluate the Efficacy and Safety of Non-racemic Amisulpride (SEP-4199) for the Treatment of Bipolar I Depression

Non-racemic amisulpride (SEP-4199) is an 85:15 ratio of aramisulpride:esamisulpride with a 5-HT7 and D2 receptor binding profile optimized for the treatment of bipolar depression. The aim of this study was to evaluate the efficacy and safety of SEP-4199 for the treatment of bipolar depression. Patients meeting DSM-5 criteria for bipolar I depression were randomized to 6 weeks of double-blind, placebo-controlled treatment with SEP-4199 200mg/d or 400mg/d. The primary endpoint was change in the Montgomery-Asberg Depression Rating Scale (MADRS) at Week 6. The primary efficacy analysis population consisted of patients in Europe and US (n=289); the secondary efficacy analysis population (ITT; n=337) included patients in Japan. Endpoint improvement in MADRS total score was observed on both the primary analysis for SEP-4199 200mg/d (P=0.054; effect size [ES], 0.31) and 400mg/d (P=0.054; ES, 0.29), and on the secondary (full ITT) analysis for SEP-4199 200mg/d (P=0.016; ES, 0.34) and 400mg/d (P=0.024; ES, 0.31). Study completion rates were 81% on SEP-4199 200mg/d, 88% on 400mg/d, and 86% on placebo. SEP-4199 had low rates of individual adverse events (<8%) and minimal effects on weight and lipids; median increases in prolactin were +83.6μg/L on 200mg/d, +95.2μg/L on 400mg/d compared with 0.0μg/L on placebo. The study excluded patients with bipolar II depression and serious psychiatric or medical comorbidity. Study results provide preliminary proof of concept, needing confirmation in subsequent randomized trials, for the efficacy of non-racemic amisulpride in bipolar depression.

Effect of Concomitant Benzodiazepine Use on Efficacy and Safety of Esketamine Nasal Spray in Patients with Major Depressive Disorder and Acute Suicidal Ideation or Behavior: Pooled Randomized, Controlled Trials

PurposeThe impact of benzodiazepines on the efficacy and safety of esketamine as a rapid-acting antidepressant remains unclear.Materials and MethodsData from two identically designed, randomized double-blind studies were pooled and analyzed on a post-hoc basis. In both studies, adults with major depressive disorder with acute suicidal ideation or behavior were randomized to placebo or esketamine 84 mg nasal spray twice-weekly for 4 weeks, each with comprehensive standard-of-care (initial hospitalization and newly initiated or optimized oral antidepressant[s]). Efficacy and safety were analyzed in two groups based on whether patients used concomitant benzodiazepines, which were prohibited within 8 hours before and 4 hours after the first dose of esketamine and within 8 hours of the primary efficacy assessment at 24 hours. The primary efficacy endpoint – change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score – was analyzed using ANCOVA.ResultsMost patients (309/451, 68.5%) used concomitant benzodiazepines. Greater decrease in MADRS total score was observed with esketamine (mean [SD]: −16.1 [11.73]) versus placebo (−12.6 [10.56]) at 24 hours (least-squares mean difference: −3.7, 95% CI: −5.76, −1.59). The differences between the esketamine and placebo groups were clinically meaningful, irrespective of benzodiazepine use (benzodiazepine: −4.3 [−6.63, −1.89]; no benzodiazepine: −3.1 [−6.62, 0.45]). Among patients taking esketamine, change in MADRS total score was not significantly different between patients taking benzodiazepines (−15.8 [11.27]) versus those not taking benzodiazepines (−16.8 [12.82]) (least-squares mean difference: 1.1, [−2.24, 4.45]). Among esketamine-treated patients, the incidence of sedation was higher with benzodiazepine use, whereas dissociation was similar.ConclusionBenzodiazepines do not meaningfully affect the rapid-acting antidepressant effect of esketamine at 24 hours post-first dose among patients with MDD and acute suicidal ideation or behavior.

Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent

To compare esketamine to placebo, each in addition to standard-of-care treatment, for rapidly reducing major depressive disorder symptoms, including suicidal ideation. This phase 3, double-blind, multicenter study (ASPIRE I), conducted between June 2017 and December 2018, enrolled 226 adults having major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) criteria, active suicidal ideation with intent, and need for psychiatric hospitalization. Patients were randomized 1:1 to esketamine 84 mg or placebo nasal spray twice-weekly for 4 weeks, each with comprehensive standard-of-care treatment (initial psychiatric hospitalization and newly initiated or optimized oral antidepressant[s] therapy). Change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score (primary endpoint) was analyzed using analysis of covariance (ANCOVA), and change in Clinical Global Impression of Severity of Suicidality Revised version (CGI-SS-r; key secondary endpoint) score was analyzed using ANCOVA on ranks with treatment difference estimated using the Hodges-Lehmann estimate. Greater improvement in MADRS total score was observed with esketamine + standard-of-care versus placebo + standard-of-care at 24 hours (least-squares mean difference [SE]: -3.8 [1.39]; 95% CI, -6.56 to -1.09; 2-sided P = .006), as well as at earlier (4 hours) and later time points during 4-week double-blind treatment. The difference between groups in the severity of suicidality was not statistically significant (median of treatment difference [95% CI]: 0.0 [-1.00 to 0.00]; 2-sided P = .107). The most common adverse events among esketamine-treated patients were dizziness, dissociation, headache, nausea, and somnolence. These findings demonstrate rapid and robust efficacy of esketamine nasal spray in reducing depressive symptoms in severely ill patients with major depressive disorder who have active suicidal ideation with intent. ClinicalTrials.gov identifier: NCT03039192.

Baseline insomnia as a predictor of antidepressant efficacy to repeated intravenous ketamine for unipolar and bipolar depression: A preliminary study

ObjectiveKetamine has been demonstrated to have robust and rapid antidepressant effects, and few studies have focused on the relationship between insomnia and the efficacy of ketamine. The objective of this study was to examine whether baseline insomnia predicted the antidepressant efficacy of repeated intravenous ketamine infusions for unipolar and bipolar depression. MethodPatients with high insomnia (n = 64) or low insomnia (n = 68) received six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days (Monday-Wednesday-Friday). The Montgomery-Asberg Depression Rating Scale (MADRS) without sleep item was used to assess depressive symptoms. Response was defined as a MADRS total score ≥ 50%, and remission was defined as a MADRS total score ≤ 10. ResultThere were no differences in response or remission rates between patients with high and low insomnia. However, the logistic regression model showed that high insomnia predicted an increased likelihood of response and remission. Cox proportional hazards models showed a reduced latency to respond and remit in patients with high insomnia. A linear mixed model showed that the high insomnia subgroup had greater improvement than the low insomnia subgroup (all p < 0.05). LimitationThe major limitation of this study is the open-label design. ConclusionWhen given six ketamine infusions, patients with high insomnia were more likely to respond and remit than those with low insomnia. Patients with high insomnia showed not only a shorter latency to respond and remit, but also greater improvement than those with low insomnia.

Experience with vortioxetine in the treatment of post-stroke depression

Post-stroke depression significantly impairs functional recovery in patients and their quality of life. Objective : to evaluate the efficacy of vortioxetine in correcting depressive symptoms in the early recovery period of ischemic stroke, as well as its effect on the cognitive functions of patients. Patients and methods. The investigation enrolled 60 patients with ischemic stroke in the carotid bed with symptoms of mild and moderate depression according to the Montgomery-Asberg Depression Rating Scale (MADRS). Group 1 (a study group) included 30 patients who received vortioxetine 10 mg/day for 8 weeks; Group 2 (a comparison group) consisted of 30 patients who refused to take an antidepressant. The investigators evaluated the severity of focal neurological deficit using the US National Institutes of Health Stroke Scale (NIHSS), the degree of functional deficit with the modified Rankin Scale (mRS) and the Functional Independence Measure (FIM). The diagnosis of poststroke depression was established according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria; the authors analyzed the severity of depression using the Hospital Anxiety and Depression Scale (HADS) and MADRS and cognitive functions with the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). For evaluation of higher mental dysfunctions, they used a set of neuropsychological techniques developed by A.R. Luria and his followers, by applying the classic stimulus materials. Results and discussion. At 8-week follow-up, in Group 1 there were no patients with symptoms of moderate depression, only 14 (46.7%) patients had symptoms of mild depression, and the remaining 16 (53.3%) patients did not have emotional disturbances. At the same time, in Group 2, 14 (46.7%) patients were observed to have signs of moderate depressive disorder and 15 (50%) had symptoms of mild depression; 1 (0.3%) patient had symptoms of major depressive disorder. During treatment with vortioxetine, there was a considerable decrease in the severity of depressive symptoms according to the total MADRS score (U=87.0; p<0.0001) and a better functional recovery after a stroke, as shown by FIM (U=296.0, p= 0.023) and NIHSS scores (p<0.05). Analyzing the MoCA subtest scores revealed that Group 1 patients statistically significantly better coped with attention tasks (U=237.0; p<0.001). Conclusion. Vortioxetine significantly reduces the severity of depressive symptoms, has an obvious positive effect on the cognitive status of patients, by improving neurodynamic functions and memory in patients in the early recovery period of ischemic stroke.

A 12-week multidomain intervention for late-life depression: a community-based randomized controlled trial

BackgroundGiven that current unimodal strategies for treating late-life depression are insufficient, the awareness of the necessity and importance of multidomain intervention has increased. We assessed the efficacy of multidomain intervention in reducing symptoms of late-life depression. MethodsThis was a 12-week community-based randomized controlled trial in 78 older adults diagnosed with major depressive disorder. Participants were randomly assigned to the multidomain intervention or supportive therapy group. We provided four home visits and 12 telephone calls over 12 weeks. Four therapeutic approaches (physical activity, healthy diet, social activity, and brief cognitive restructuring) were incorporated into the multidomain intervention. The primary outcome was the change in depressive symptoms, as measured by the Montgomery–Asberg Depression Rating Scale (MADRS). Secondarily, we investigated changes in resting-state functional connectivity. ResultsThe MADRS total score was reduced more in the multidomain intervention group than in the supportive therapy group during the 12 weeks (intervention × time interaction, P = =0.007). After correction for multiple comparisons, the multidomain intervention group exhibited a lower MADRS total score at week 12 (score difference 5.117; P = =0.029). At follow-up, the multidomain intervention group also exhibited less functional connectivity between the posterior cingulate cortex and left inferior parietal lobule within the default mode network (FDR < 0.1). LimitationsCaution is needed in the interpretation of the results, considering the small sample size and high percentage of female participants. ConclusionsA 12-week multidomain intervention resulted in a greater reduction of depressive symptoms among the elderly with major depressive disorder than their counterparts who received supportive therapy.

Associations between cognitions and functional decline in patients with major depressive disorder

Associations between cognitions and functional decline in patients with major depressive disorder

Efficacy of Adjunctive Infliximab vs Placebo in the Treatment of Adults With Bipolar I/II Depression

To our knowledge, no study has previously evaluated whether individuals with bipolar depression enriched a priori on the basis of biochemical and/or phenotypic immuno-inflammatory activation would differentially respond to an anti-inflammatory agent for the treatment of depressive symptoms. To assess the antidepressant efficacy of adjunctive infliximab, a monoclonal antibody targeting tumor necrosis factor, in adults with bipolar I and bipolar II depression and inflammatory conditions. This 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at 2 outpatient tertiary care sites in Canada and the United States. Eligible adults (aged 18-65 years) met DSM-5-defined criteria for bipolar I or bipolar II depression and exhibited pretreatment biochemical and/or phenotypic evidence of inflammatory activation. Participants were enrolled between October 1, 2015, and April 30, 2018. Data analysis was performed from May 1 through July 31, 2018, using modified intent-to-treat analysis. Patients were randomized to receive 3 intravenous infusions of infliximab therapy or placebo at baseline and at weeks 2 and 6 of the 12-week study. The primary efficacy outcome was baseline-to-end point (ie, week-12) change in Montgomery-Asberg Depression Rating Scale (MADRS) total score. History of childhood maltreatment, as assessed by the Childhood Trauma Questionnaire, was used for exploratory analyses as 1 of several secondary outcomes. A total of 60 participants were randomized to infliximab (n = 29 [48%]; mean [SD] age, 45.0 [11.7] years; 20 of 28 female [71%]) or to placebo (n = 31 [52%]; mean [SD] age, 46.8 [10.2] years; 26 of 30 female [87%]) across study sites. Overall baseline-to-end point change in MADRS total score was observed across treatment × time interaction (χ2 = 10.33; P = .04); reduction in symptom severity was not significant at week 12 (relative risk, 1.09; 95% CI, 0.80-1.50; df = 1; P = .60). As part of a secondary analysis, a significant treatment × time × childhood maltreatment interaction was observed in which infliximab-treated individuals with childhood history of physical abuse exhibited greater reductions in MADRS total score (χ2 = 12.20; P = .02) and higher response rates (≥50% reduction in MADRS total score) (χ2 = 4.05; P = .04). Infliximab did not significantly reduce depressive symptoms compared with placebo in adults with bipolar depression. Results from secondary analyses identified a subpopulation (ie, those reporting physical and/or sexual abuse) that exhibited a significant reduction in depressive symptoms with infliximab treatment compared with placebo. ClinicalTrials.gov identifier: NCT02363738.

EFFICACY AND SAFETY OF ESKETAMINE NASAL SPRAY PLUS AN ORAL ANTIDEPRESSANT IN ELDERLY PATIENTS WITH TREATMENT-RESISTANT DEPRESSION

Introduction Estimates of 18-40% of elderly patients with depression suffer from treatment-resistant depression (TRD), defined as non-response to at least two antidepressants. Elderly patients experience greater disability and functional decline, decreased quality of life, and greater mortality from suicide than younger patients. Esketamine nasal spray is being investigated for treatment of TRD. We evaluated the efficacy, safety, and tolerability of flexibly dosed esketamine nasal spray (ESK) (28 mg, 56 mg or 84 mg) plus a newly initiated oral antidepressant (AD), compared with AD plus placebo nasal spray (PBO), for the treatment of TRD in elderly patients. Post hoc analyses, performed to better assess the data from this first large clinical trial of TRD in the elderly, are presented in the companion abstract. Methods Patients ≥ 65 years of age (N=138) in this phase 3, double-blind, multicenter, active-controlled study (NCT02422186) were randomized (1:1) to either ESK + AD (n=72) or AD + PBO (n=66). The primary endpoint was the change in the Montgomery–Asberg Depression Rating Scale (MADRS) total score from day 1 (baseline) to the end of a 4-week double-blind treatment phase. Statistical analysis employed mixed-effects model for repeated measures (MMRM), with a weighted combination test to account for an interim analysis for sample size re-estimation, using a one-sided 0.025 significance level. Pre-specified subgroup analyses were performed for ages 65-74 years (n=116) and ≥75 years (n=21). Remote raters, blinded to the treatment arm, conducted the MADRS assessments by telephone. Results The mean (SD) patient age was 70.0 (4.52) years and mean (SD) baseline MADRS total score was 35.2 (6.16). The mean (SD) change in MADRS total scores from baseline to day 28 was -10.0 (12.74) for ESK + AD and -6.3 (8.86) for AD + PBO. Based on MMRM analysis, the median-unbiased estimate of the difference between ESK + AD and AD + PBO was -3.6 (95% CI: -7.20, 0.07; one-sided p=0.029). A treatment difference favoring ESK+AD was seen for the 65-74 years subgroup. The difference in LS mean (SE) change at day 28 was -4.9 (2.04) for 65-74 years (one-sided p=0.009) and -0.4 (5.02) for ≥75 years (one-sided p=0.465). The most common treatment-emergent adverse events (TEAEs) in the ESK + AD group were dizziness (20.8%), nausea (18.1%), headache, fatigue, increased blood pressure, dissociation (12.5% each) and vertigo (11.1%). The most common TEAEs in the AD + PBO group were anxiety, dizziness and fatigue (7.7% each). Conclusions While treatment with ESK + AD did not demonstrate a statistically significant difference vs treatment with AD + PBO using the weighted combination test on the primary outcome, a statistically significant treatment effect was observed for patients aged 65-74 years, but not for the limited number of patients aged ≥75 years. Safety results were consistent with previous studies in younger adult populations; no new safety concerns were identified. This study was funded by Janssen Research & Development, LLC. This research was funded by Janssen Research & Development, LLC

The Psychometric Properties of the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) in Patients with HBV-Related Liver Disease.

BackgroundComorbid depression in Hepatitis B virus (HBV) is common. Developing accurate and time- efficient tools to measure depressive symptoms in HBV is important for research and clinical practice in China.AimsThis study tested the psychometric properties of the Chinese version of the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR) in HBV patients.MethodsThe study recruited 245 depressed patients with HBV and related liver disease. The severity of depressive symptoms was assessed with the Montgomery-Asberg Depression Rating Scale (MADRS) and the QIDS-SR.ResultsInternal consistency (Cronbach’s alpha) was 0.796 for QIDS-SR. The QIDS-SR total score was significantly correlated with the MADRS total score (r=0.698, p<0.001). The QIDS-SR showed unidimensional measurement properties in exploratory factor analysis.ConclusionsThe QIDS-SR (Chinese version) has good psychometric properties in HBV patients and appears to be useful in assessing depression in clinical settings.

Clinical validation of the Psychotic Depression Assessment Scale (PDAS) against independent global severity ratings in older adults.

According to a recent study, ratings on the Psychotic Depression Assessment Scale (PDAS) obtained via a dedicated semi-structured interview are valid measures of the severity of psychotic depression. This study aimed to further test the validity, scalability and responsiveness of the PDAS in older adults using independent ratings on the Clinical Global Impression Scale - Severity (CGI-S) and the Montgomery-Asberg Depression Rating Scale (MADRS) as references. Ratings were performed at admission and discharge at two old age psychiatric wards in Flanders, Belgium. In total, 62 older adults (mean age: 74.3 years) with psychotic depression were included. The PDAS was rated by trained nurses using the semi-structured PDAS interview. Senior psychiatrists scored the participants on the CGI-S. Psychologists or experienced nurses rated participants on the MADRS. Clinical validity was assessed by correlating the PDAS total scores with CGI-S ratings and MADRS total scores. Mokken analysis was performed to assess the scalability of the PDAS. Responsiveness was assessed by comparing the proportion of participants in remission (PDAS total score <8 at study baseline and endpoint). The Spearman correlation coefficients were 0.76 and 0.79 for the PDAS versus CGI-S and PDAS versus MADRS, respectively. The Mokken analysis yielded a Loevinger coefficient of 0.46, which is indicative of scalability. At admission, no participants met the PDAS remission criterion. At discharge, 54% (95% confidence interval: 47%-60%) of the patients met this criterion. The PDAS appears to be a clinically valid, scalable and responsive measure of the severity of psychotic depression in older adults.

S100B, Homocysteine, Vitamin B12, Folic Acid, and Procalcitonin Serum Levels in Remitters to Electroconvulsive Therapy: A Pilot Study.

Background Electroconvulsive therapy (ECT) is one of the most effective treatment options for refractory depressed patients. To date, there are only a few predictors of response. Aim The aim was to identify predictive biomarkers of remission to ECT on a molecular level. Methods 11 patients suffering from a major depressive episode—according to the Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)—underwent 10 ECT sessions. Blood samples were taken, and the depression severity was assessed before, one hour and 24 hours after sessions 1, 4, 7, and 10 using the Montgomery Asberg Depression Rating Scale (MADRS). A MADRS total score < 12 was interpreted as remission. Results Patients remitting under ECT had significantly higher homocysteine (p < 0.001), S100B (p < 0.001), and procalcitonin (PCT) (p = 0.027) serum levels. On the contrary, serum levels of vitamin B12 (p < 0.001) and folic acid (p = 0.007) were significantly lower in remitters compared to those in nonremitters. Levels remained unchanged throughout the whole ECT course. Conclusions Our findings indicate that lower levels of vitamin B12 and folic acid associated with higher levels of homocysteine, S100B, and PCT point to a subgroup of depressed patients sensitive to ECT. Due to the limited sample size, further studies are required to replicate our findings.

Efficacy and tolerability of different doses of three new antidepressants for treating major depressive disorder: A PRISMA-compliant meta-analysis

In last decade, the US FDA has approved three new antidepressants: vortioxetine, levomilnacipran, and vilazodone. Many studies have researched the effects of these antidepressants on major depressive disorder (MDD), but they have not determined the optimum dosage. This meta-analysis investigated the efficacies of these three drugs at different dosages in the treatment of MDD. The PubMed, Embase, Cochrane Library, psycINFO, and ClinicalTrials.gov databases were searched to identify relevant literature. The primary outcomes were efficacy [quantified as the change from baseline in total score on the Montgomery-Asberg Depression Rating Scale (MADRS)] and tolerability (discontinuations due to adverse events). The effect size was quantified as the weighted mean difference for continuous data and the risk ratio (RR) for dichotomous data. Overall 22 studies were included. The changes in the MADRS total score were significantly higher for vortioxetine at 5, 10, 20, and 10–20 mg/day than for placebo. The tolerability was significantly worse for 20 mg/day vortioxetine than for placebo (RR = 1.84, 95% confidence interval = 1.13 to 3.02). In addition, increasing the dosage improved the efficacy of vortioxetine but worsened the tolerability. Levomilnacipran and vilazodone at any dosage produced a significantly higher mean change from baseline in the MADRS total score and a worse tolerability than for placebo. In conclusion, considering both efficacy and tolerability, 10 mg/day vortioxetine might be optimal for the treatment of MDD. The long-term efficacy and safety of vortioxetine needed to be investigated, and more studies of levomilnacipran and vilazodone are needed to define their optimal dosages.

Resilience and spirituality in patients with depression and their family members: A cross-sectional study

ObjectiveThe degree and quality of resilience in patients with depression have never been investigated in the context of remission status, spirituality/religiosity, and family members' resilience levels, which was addressed in this study. MethodsThis cross-sectional study recruited Japanese outpatients with depressive disorder according to ICD-10 and cohabitant family members who were free from psychiatric diagnoses. Resilience was assessed using the 25-item Resilience Scale (RS). Other assessments included the Montgomery-Asberg Depression Rating Scale (MADRS); the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT) and Kasen et al.'s (2012) scale for spirituality/religiosity; and the Rosenberg Self-Esteem Scale (RSES). ResultsOne hundred outpatients with depression (mean±SD age, 50.8±14.5years; 44 men; MADRS total score 9.8±9.0) and 36 healthy family members (mean±SD age, 56.5±15.0years; 18 men) were included. Symptom severity, attendance at religious/spiritual services, and self-esteem were significantly associated with RS scores in the patient group. RS total scores were significantly higher in remitted patients compared to non-remitted patients (mean±SD, 112.3±17.1 vs. 84.8±27.7, p<0.001). No correlation was found in RS total scores between patients and their family members (p=0.265), regardless of patients' remission status. ConclusionsResilience may be influenced by individual characteristics rather than familial environment; furthermore, self-esteem or spirituality/religiosity may represent reinforcing elements. While caution is necessary in extrapolating these findings to other patient populations, our results suggest that resilience may be considered a state marker in depression.

What does the MADRS mean? Equipercentile linking with the CGI using a company database of mirtazapine studies

BackgroundLittle is known about the clinical relevance of the Montgomery Asberg Depression Rating Scale (MADRS) total scores. It is unclear how total scores translate into clinical severity, or how commonly used measures for response (reduction from baseline of ≥50% in the total score) translate into clinical relevance. Moreover, MADRS based definitions of remission vary. MethodsWe therefore compared: a/ the MADRS total score with the Clinical Global Impression – Severity Score (CGI-S) b/ the percentage and absolute change in the MADRS total scores with Clinical Global Impression – Improvement (CGI-I); c/ the absolute and percentage change in the MADRS total scores with CGI-S absolute change. The method used was equipercentile linking of MADRS and CGI ratings from 22 drug trials in patients with Major Depressive Disorder (MDD) (n=3288). ResultsOur results confirm the validity of the commonly used measures for response in MDD trials: a CGI-I score of 2 (‘much improved’) corresponded to a percentage MADRS reduction from baseline of 48–57%, and a CGI-I score of 1 (‘very much improved’) to a reduction of 80–84%. If a state of almost complete absence of symptoms were required for a definition of remission, a MADRS total score would be <8, because such scores corresponded to a CGI-S score of 2 (‘borderline mentally ill’). Limitations: Although our analysis is based on a large number of patients, the original trials were not specifically designed to examine our research question. ConclusionsThe results might contribute to a better understanding and improved interpretation of clinical trial results in MDD.

P.2.f.009 - Antidepressant augmentation and co-initiation treatment in acute major depressive disorder: a systematic review, meta-analysis and metaregression analysis

This phase 2 study examined the efficacy and tolerability of edivoxetine, a highly selective norepinephrine reuptake inhibitor, as an adjunctive treatment for patients with major depressive disorder (MDD) who have a partial response to selective serotonin reuptake inhibitor (SSRI) treatment.Study design consisted of double-blind, 10-week therapy of adjunctive edivoxetine (6–18 mg once daily) or adjunctive placebo with SSRI. Inclusion/entry criteria included partial response to current SSRI by investigator opinion and a GRID 17-item Hamilton Rating Scale for Depression (HAMD17) total score ≥16. The primary efficacy measure was the Montgomery–Asberg Depression Rating Scale (MADRS). Safety measures included treatment-emergent adverse events (TEAE) and vital signs.For the primary evaluable population (n=63 for adjunctive edivoxetine and n=68 for adjunctive placebo), the treatment groups did not differ significantly on the primary outcome of change from baseline to week 8 in the MADRS total score; the effect size of edivoxetine treatment was 0.26. Significant treatment differences, favoring adjunctive edivoxetine (p≤.05), were shown for improvements in role functioning and the functional impact of fatigue. For the adjunctive edivoxetine randomized group (N=111), the most frequent TEAEs were hyperhidrosis (7.2%), nausea (7.2%), erectile dysfunction (6.3%) and testicular pain (6.3%). Hemodynamic changes were observed in blood pressure and pulse rate between treatment groups.Study was underpowered for an alpha 2-sided 0.05 significance level for the primary outcome.For patients with MDD who had a partial response to SSRIs, adjunctive edivoxetine treatment was not statistically superior to adjunctive placebo on the primary outcome measure. However, pending further study, improved functioning and remission rate suggest a potential role for edivoxetine for patients with depression.

Does early improvement in depressive symptoms predict subsequent remission in patients with depression who are treated with duloxetine?

PurposeIn this prospective study, we examined whether early reduction in depressive symptoms predicts later remission to duloxetine in the treatment of depression, as monitored using the Montgomery–Asberg Depression Rating Scale (MADRS).Patients and methodsAmong the 106 patients who were enrolled in this study, 67 were included in the statistical analysis. A clinical evaluation using the MADRS was performed at weeks 0, 4, 8, 12, and 16 after commencing treatment. For each time point, the MADRS total score was separated into three components: dysphoria, retardation, and vegetative scores.ResultsRemission was defined as an MADRS total score of ≤10 at end point. From our univariate logistic regression analysis, we found that improvements in both the MADRS total score and the dysphoria score at week 4 had a significant interaction with subsequent remission. Furthermore, age and sex were significant predictors of remission. There was an increase of approximately 4% in the odds of remission for each unit increase in age, and female sex had an odds of remission of 0.318 times that of male sex (remission rate for men was 73.1% [19/26] and for women 46.3% [19/41]). However, in the multivariate model using the change from baseline in the total MADRS, dysphoria, retardation, and vegetative scores at week 4, in which age and sex were included as covariates, only sex retained significance, except for an improvement in the dysphoria score.ConclusionNo significant interaction was found between early response to duloxetine and eventual remission in this study. Sex difference was found to be a predictor of subsequent remission in patients with depression who were treated with duloxetine, with the male sex having greater odds of remission.