Adult Major Depressive Disorder Research Articles

Comparative efficacy and safety of 4 atypical antipsychotics augmentation treatment for major depressive disorder in adults: A systematic review and network meta-analysis.

Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant therapy (ADT). We aimed to compare and rank the efficacy and safety of 4 AAPs in the adjuvant treatment of MDD. We searched randomized controlled trials (RCTs) published and unpublished from the date of databases and clinical trial websites inception to April 30, 2023. The evidence risk of bias (RoB) and certainty are assessed using the Cochrane bias risk tool and grading of recommendations assessment, development, and evaluation (GRADE) framework, respectively. Using network meta-analysis, we estimated summary risk ratios (RRs) or standardized mean difference (SMD) based on the random effects model. 56 eligible studies comprising 11448 participants were included. In terms of primary efficacy outcome, compared with placebo (PBO), all AAPs had significant efficacy (SMD = -0.40; 95% CI, -0.68 to -0.12 for quetiapine (QTP); -0.35, -0.59 to -0.11 for olanzapine (OLA); -0.28, -0.47 to -0.09 for aripiprazole (ARI) and -0.25, -0.42 to -0.07 for brexpiprazole (BRE), respectively). In terms of acceptability, no significant difference was found, either agents versus agents or agents versus PBO. In terms of tolerability, compared with the PBO, QTP (RR = 0.24; 95% CI,0.11-0.53), OLA (0.30,0.10-0.55), ARI (0.39,0.22-0.69), and BRE (0.37,0.18-0.75) were significantly less well tolerated. 8 (14.2%) of 56 trials were assessed as low RoB, 38 (67.9%) trials had moderate RoB, and 10 (17.9%) had high RoB; By the GRADE, the certainty of most evidence was low or very low. Adjuvant AAPs had significant efficacy compared with PBO, but treatment decisions must be made to balance the risks and benefits.

Physical exercise and major depressive disorder in adults: systematic review and meta-analysis

The objective of this study was to assess the benefits and potential risks associated with different physical exercise modalities for managing symptoms in adults with major depressive disorder who were not receiving second-generation antidepressants or cognitive behavioral therapy. A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted. The search included multiple databases: Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, PsycInfo, Web of Science, Clinical Trials repository, gray literature, and manual search. No language restrictions were applied. Eligible studies involved RCTs of adults with major depressive disorder who were not on antidepressants or receiving psychological therapy, comparing various exercise modalities with second-generation antidepressants or cognitive behavioral therapy, body-mind exercise, or no exercise interventions. Nine RCTs involving 678 adults were analyzed. The pooled results indicated a small clinical effect favoring exercise in reducing depressive symptoms, although the difference was not statistically significant (SMD = 0.27, 95% CI [− 0.58, 0.04], P = 0.09). Subgroup analyses suggested that intervention duration, frequency, intensity, supervision, age, overweight/obesity status, and diagnosis of depression could influence treatment outcomes. A sensitivity analysis was conducted for studies with controls without exercise interventions and a low risk of bias in the domains related to the randomization process and deviations from the intended interventions. The results showed that there are no statistically significant differences when interventions are compared with medication and body-mind exercise (p = 0.12, I2 = 78%). Furthermore, the analysis showed a moderate effect size favoring exercise, but no statistically significant difference between groups (p = 0.05), with high heterogeneity (I2 = 85%). The evidence quality was generally low to very low, and methodological limitations compromised the certainty of the findings. Adverse events associated with exercise were manageable. The study emphasizes the need for well-designed RCTs to provide clearer insights into the potential benefits of exercise in managing major depressive disorder symptoms. Caution is warranted in interpreting these results due to the limitations of the included studies.Systematic review registration: PROSPERO CRD42022356741.

Efficacy and tolerability of desvenlafaxine in the real-world treatment of patients with major depression: a narrative review and an expert opinion paper

ABSTRACT Introduction Major depressive disorder (MDD) is a common severe mental disorder, requiring a tailored and integrated treatment. Several approaches are available including different classes of antidepressants various psychotherapeutic approaches, and psychosocial interventions. The treatment plan for each patient with MDD should be differentiated on the basis of several clinical, personal, and contextual factors. Areas covered Desvenlafaxine – a serotonine-noradrenergic reuptake inhibitor (SNRI) antidepressant – has been approved in the United States in 2008 for the treatment of MDD in adults, and has been recently rediscovered by clinicians due to its good side-effect profile and its clinical effectiveness. A narrative review on efficacy, tolerability and use of desvenlafaxine in clinical practice was carried out. The keywords: ‘major depression’, ‘depression,’ ‘desvenlafaxine,’ ‘efficacy,’ ‘clinical efficacy,’ ‘side effects’, ‘tolerability,’ ‘elderly patients’, ‘consultation-liaison’, ‘menopausal’, ‘young people’, ‘adolescent’ were entered in PubMed, ISI Web of Knowledge, Scopus and Medline. No time limit was fixed, the search strategy was implemented on May 10, 2023. Expert opinion Desvenlafaxine should be listed among the optimal treatment strategies for managing people with MDD, whose main strengths are: 1) ease of dosing; 2) favorable safety and tolerability profile, 3) absence of sexual dysfunctions, weight gain and low rate of discontinuation symptoms; 4) low risk of drug–drug interactions.

Lateralized grey matter volume changes in adolescents versus adults with major depression: SDM-PSI meta-analysis

The current study is the first meta-analysis to examine grey matter volume (GMV) changes in adolescents and across the lifespan in major depressive disorder (MDD). Seed-based d mapping–with permutation of subject images (SDM-PSI) has advantages over previous coordinate-based meta-analytical methods (CBMA), such as reducing bias (via the MetaNSUE algorithm) and including non-statistically significant unreported effects. SDM-PSI was used to analyze 105 whole-brain GMV voxel-based morphometry (VBM) studies comparing 6,530 individuals with MDD versus 6,821 age-matched healthy controls (HC). A laterality effect was observed in which adults with MDD showed lower GMV than adult HC in left fronto-temporo-parietal structures (superior temporal gyrus, insula, Rolandic operculum, and inferior frontal gyrus). However, these abnormalities were not statistically significant for adolescent MDD versus adolescent HC. Instead, adolescent MDD showed lower GMV than adult MDD in right temporo-parietal structures (angular gyrus and middle temporal gyrus). These regional differences may be used as potential biomarkers to predict and monitor treatment outcomes as well as to choose the most effective treatments in adolescents versus adults. Finally, due to the paucity of youth, older adult, and longitudinal studies, future studies should attempt to replicate these GMV findings and examine whether they correlate with treatment response and illness severity.

Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder.

Depression is a significant cause of morbidity and mortality globally. Although various pharmacologic options exist for depression, treatments are limited by delayed or incomplete therapeutic response, low rates of remission, and adverse effects necessitating effective, fast-acting, and better tolerated alternatives. The purpose of this review is to describe the safety and efficacy of dextromethorphan-bupropion (Auvelity), a Food and Drug Administration approved treatment for major depressive disorder in adults. Dextromethorphan modulates glutamate signaling through uncompetitive antagonism of N-methyl-D-aspartate receptors and sigma-1 agonism, while bupropion increases the bioavailability of dextromethorphan by CYP2D6 inhibition. In a phase 3 trial with dextromethorphan-bupropion 45-105 mg for patients with major depressive disorder saw significant reductions in their Montgomery-Åsberg Depression Rating Scale total scores compared to placebo. A phase 2 trial comparing dextromethorphan-bupropion 45-105 mg to bupropion monotherapy led to significant reduction in Montgomery-Åsberg Depression Rating Scale score. Changes in Montgomery-Åsberg Depression Rating Scale with dextromethorphan-bupropion were seen within two weeks in both clinical trials. Remission and response rates were significantly higher with dextromethorphan-bupropion in both studies. The medication was well-tolerated in both trials, with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with dextromethorphan-bupropion saw large reductions in Montgomery-Åsberg Depression Rating Scale scores that were maintained through 12 and 15 months of treatment. In both long-term studies, remission rates approached 70%, while response rates were greater than 80%. These data suggest that dextromethorphan-bupropion is an effective, fast-acting, and well tolerated option for depression treatment and produced remission in a large percentage of patients.

The Burden of Attention-Deficit/Hyperactivity Disorder Traits in Adult Patients with Major Depressive Disorder in Japan.

Symptoms of attention-deficit/hyperactivity disorder (ADHD) often overlap with and are hidden by those of mood disorders, including major depressive disorder (MDD), resulting in adult ADHD patients being misdiagnosed as MDD. This study aims to examine if diagnosed MDD patients are more likely to exhibit ADHD traits and if the presence of ADHD traits increases the humanistic burden, including the impairment of health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), and health-care resource utilization (HRU), on MDD patients in Japan. This study utilized existing National Health and Wellness Survey (NHWS) data. The 2016 Japan NHWS is an internet-based survey comprising a total of 39,000 respondents, including those with MDD and/or ADHD. A randomly selected subset of the respondents responded to the Japanese-version Adult ADHD self-report scale (ASRS-v1.1; ASRS-J) symptom checklist. Respondents were considered ASRS-J-positive if the total score was ≥36. The HRQoL, WPAI, and HRU were assessed. Among MDD patients (n = 267), 19.9% were screened ASRS-J-positive, while 4.0% of non-MDD respondents (n = 8885) were ASRS-J-positive. There was a significant association between MDD status and ASRS-J status (crude odds-ratio [OR]: 5.9) as well as between MDD status and ADHD-diagnosis status (crude OR: 22.6). MDD patients who were ASRS-J positive experienced significantly lower HRQoL and higher WPAI than those who were ASRS-J negative. Limitations of this study include potential recall bias owing to the self-report nature of the survey and lack of objective confirmation of MDD diagnosis through review of medical records. This study demonstrated a significant association between MDD status and exhibiting ADHD traits. Adult MDD patients screened ASRS-J-positive experienced significantly higher humanistic burden than patients screened ASRS-J-negative. Our results emphasize the importance of ensuring appropriate screening of ADHD and looking out for potentially hidden ADHD symptoms when diagnosing and treating MDD in adulthood.

Ego-defense mechanisms and brief psychotherapies for the management of major depressive disorder in adults: A longitudinal and quasi-experimental study

ObjectiveTo evaluate the effect of psychotherapies on ego defense mechanisms and the reduction of depressive symptoms in a 12-month follow-up period. MethodsThis longitudinal and quasi-experimental study nested within a randomized clinical trial included a clinical sample of adults (18–60 years) diagnosed with major depressive disorder using the Mini-International Neuropsychiatric Interview. Two models of psychotherapy were used: Supportive Expressive Dynamic Psychotherapy (SEDP) and Cognitive Behavioral Therapy (CBT). Defense Style Questionnaire 40 was used to analyze defense mechanisms and the Beck Depression Inventory was used to measure the depressive symptoms. ResultsThe total sample comprised 195 patients (113 SEDP and 82 CBT), with the mean age was 35.63 (11.44) years. After adjustments, increased mature defenses was significantly associated with reduced depressive symptoms at all follow-up times (p < 0.001) and the decrease in immature defenses was significantly associated with the reduction of depressive symptoms at all follow-up times (p < 0.001). While neurotic defenses were not associated with a reduction in depressive symptoms at any time of follow-up (p > 0.05). ConclusionBoth models of psychotherapy were effective in increasing mature defenses and decreasing immature ones, as well as decreasing depressive symptoms at all evaluation times. With this, it is understood that a greater understanding of these interactions will allow a more adequate diagnostic and prognostic evaluation and the design of useful strategies that adapt to the patient's reality.

Co-expression network of mRNA and DNA methylation in first-episode and drug-naive adolescents with major depressive disorder.

We explored the DNA methylation and messenger RNA (mRNA) co-expression network and hub genes in first-episode, drug-naive adolescents with major depressive disorder (MDD). To preliminarily explore whether adolescent MDD has unique mechanisms compared with adult MDD. We compared DNA methylation and mRNA profiles of peripheral blood mononuclear cells from four first-episode and drug-naive adolescents with MDD and five healthy adolescent controls (HCs). We performed differential expression analysis, constructed co-expression network, and screened the hub genes. And enrichment analysis was performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We also downloaded DNA methylation and mRNA datasets of adults with MDD (GSE113725/GSE38206) from the GEO database, and performed differential expression and enrichment analysis. Our clinical data showed that 3034 methylation sites and 4190 mRNAs were differentially expressed in first-episode, drug-naive adolescents MDD patients compared with HCs. 19 hub genes were screened out according to the high degree value in the co-expression network. The results from the GEO database showed that compared with adult HCs, there were 290 methylation sites and 127 mRNAs were differentially expressed in adult MDD patients. Compared with adolescent HCs and adult MDD patients, the DNA methylation and mRNA expression patterns of first-episode, drug-naive adolescent MDD patients were different. The co-expression network of DNA methylation and mRNA and the screened hub genes may play an important role in the pathogenesis of MDD in first-episode, drug-naive adolescents. Compared with adult MDD, adolescent MDD is more enriched in metabolism in terms of function and pathways.

Association between inflammatory cytokines and symptoms of major depressive disorder in adults.

This study investigated the association between inflammatory cytokines and major depressive disorder. Plasma biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Statistical analysis of baseline biomarkers in the major depression disorder (MDD) group and healthy controls (HC) group, and differences in biomarkers before and after treatment. Spearman analysis was performed to correlate baseline and after treatment MDD biomarkers with the 17-item Hamilton Depression Rating Scale (HAMD-17) total scores. Receiver operator characteristic (ROC) curves were analyzed for the effect of biomarkers on MDD and HC classification and diagnosis. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were significantly higher in the MDD group than in the HC group, while high mobility group protein 1 (HMGB1) levels were significantly lower in the MDD group. The AUCs for HMGB1, TNF-α, and IL-6 were 0.375, 0.733, and 0.783, respectively, according to the ROC curves. MDD patients with brain-derived neurotrophic factor precursor (proBDNF) levels were positively correlated with total HAMD-17 scores. The levels of proBDNF levels were positively correlated with the total HAMD-17 score in male MDD patients, and brain-derived neurotrophic factor (BDNF) and interleukin 18 (IL-18) levels were negatively correlated with the total HAMD-17 score in female MDD patients. Inflammatory cytokines are associated with the severity of MDD, and TNF-α and IL-6 have the potential as objective biomarkers to aid in the diagnosis of MDD.

Design and rationale of the REStoring mood after early life trauma with psychotherapy (RESET-psychotherapy) study: a multicenter randomized controlled trial on the efficacy of adjunctive trauma-focused therapy (TFT) versus treatment as usual (TAU) for adult patients with major depressive disorder (MDD) and childhood trauma

BackgroundMajor depressive disorder (MDD) is a common, recurrent mental disorder and a leading cause of disability worldwide. A large part of adult MDD patients report a history of childhood trauma (CT). Patients with MDD and CT are assumed to represent a clinically and neurobiologically distinct MDD subtype with an earlier onset, unfavorable disease course, stress systems’ dysregulations and brain alterations. Currently, there is no evidence-based treatment strategy for MDD that specifically targets CT. Given the central role of trauma in MDD patients with CT, trauma-focused therapy (TFT), adjunctive to treatment as usual (TAU), may be efficacious to alleviate depressive symptoms in this patient population.MethodsThe RESET-psychotherapy study is a 12-week, single-blind, randomized controlled trial testing the efficacy of TFT in 158 adults with moderate to severe MDD, as a ‘stand-alone’ depression diagnosis or superimposed on a persistent depressive disorder (PDD), and CT. TFT (6–10 sessions of Eye Movement Desensitization and Reprocessing and/or imagery rescripting) + TAU is compared to TAU only. Assessments, including a wide range of psychological/psychiatric and biological characteristics, take place before randomization (T0), during treatment (T1), at post-treatment (T2) and at 6-month follow-up (T3). Pre-post treatment stress-related biomarkers in hair (cortisol) and blood (epigenetics and inflammation) will be assessed to better understand working mechanisms of TFT. A subgroup of 60 participants will undergo structural and functional Magnetic Resonance Imaging (MRI) assessments to determine pre-post treatment brain activity. The primary outcome is self-reported depression symptom severity at post-treatment, measured with the 30-item Inventory of Depressive Symptomatology – Self Report (IDS-SR).DiscussionIf adjunctive TFT efficaciously alleviates depressive symptoms in MDD patients with CT, this novel treatment strategy could pave the way for a more personalized and targeted MDD treatment.Trial registrationClinicalTrials.gov, registered at 08–12-2021, number of identification: NCT05149352.

A comparative evaluation of resting state proxies of sympathetic and parasympathetic nervous system activity in adolescent major depression.

Major depressive disorder (MDD) is associated with autonomic nervous system (ANS) dysfunction, characterized by decreased parasympathetic (PNS) and increased sympathetic (SNS) activity. Although findings on reduced PNS activity in adult MDD have been replicated in adolescents, comprehensive studies assessing PNS and SNS proxies in underage patients with MDD are scarce. Proxies of resting PNS (heart rate variability (HRV) and SNS activity (skin conductance response [SCR] and salivary alpha amylase [sAA], as well as mixed activity (heart rate [HR]) were collected in adolescents with MDD (n = 29) and non-depressed controls (n = 29). Primary analyses addressed differences between groups and correlations with depression severity. Patients with MDD showed significantly decreased HRV (g = -0.87; 95% CI [-1.39; -0.35]) and increased HR (g = 0.66; 95% CI [0.14; 1.18]). Proxies of pure SNS activity showed no significant differences between groups. HR (positive) and HRV (negative) were significantly correlated with self- and clinician-rated depression severity. Alterations of ANS activity are evident in adolescent MDD, but characterized by decreased PNS activity only. We found no evidence for altered SNS activity. Findings suggest that ANS dysfunction early in the course of MDD might be predominantly driven by decreased PNS activity.

Safety and feasibility of faecal microbiota transplant for major depressive disorder: study protocol for a pilot randomised controlled trial

BackgroundMental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain-axis is now recognised as playing a role in mental and brain health, and promising preclinical and clinical data suggest Faecal Microbiota Transplants (FMT) may be efficacious for treating a range of mental illnesses. However, there are no existing published studies in humans evaluating the efficacy of FMT for MDD.Methods and designThis protocol describes an 8-week, triple-blind, 2:1 parallel group, randomised controlled pilot trial (n = 15), of enema-delivered FMT treatment (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. There will be a further 26-week follow-up to monitor longer-term safety. Participants will receive four FMT or placebo enemas over four consecutive days. The primary aims of the study are to evaluate feasibility and safety of FMT as an adjunctive treatment for MDD in adults. Changes in gut microbiota will be assessed as a secondary outcome. Other data will be collected, including changes in depression and anxiety symptoms, and safety parameters.DiscussionModification of the microbiota-gut-brain axis via FMT is a promising potential treatment for MDD, but there are no published rigorous clinical trials evaluating its use. If this study finds that our FMT strategy is safe and feasible, a larger fully powered RCT is planned. Further high-quality research in this field is urgently needed to address unmet need.Trial registrationAustralian and New Zealand Clinical Trials Registry: ACTRN12621000932864

A 6-week, phase IIb, randomized, double-blind, placebo-controlled trial of Anyu Peibo capsules for the treatment of major depressive disorder in adults.

Almost one-third of patients with major depressive disorder (MDD) do not respond to conventional antidepressants, and new treatments for MDD are urgently needed. This phase IIb clinical trial was designed to evaluate the efficacy and safety of Anyu Peibo capsules in the treatment of adults with MDD. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study. A total of 172 patients with MDD from nine study centers were randomized (1:1) to receive placebo (n = 86) or oral Anyu Peibo capsules (0.8 g) twice per day (n = 86) for 6 weeks. The primary endpoint was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to week 6, analyzed using an analysis of covariance (ANCOVA) approach with the baseline MADRS score, center effect and center by group interaction as the covariates. Other efficacy endpoints and variables included clinical response and remission rates according to the MADRS and the 17-item Hamilton Depression Rating Scale (HAMD-17) scores, the change in the HAMD-17, Clinical Global Impression - Severity scale and Clinical Global Impression - Improvement scale scores and the reduction in the Hamilton Anxiety Scale from baseline to week 6. The mean baseline MADRS total scores were 29.20 and 29.72 in the Anyu Peibo (n = 82) and placebo groups (n = 81), respectively. The least squares mean change in the MADRS score from baseline to week 6 was 16.59 points in the Anyu Peibo group and 14.51 points in the placebo group. Although there were greater reductions in the MADRS score from baseline to week 6 in the Anyu Peibo capsule group compared to the placebo group, the difference did not reach statistical significance (least-squares mean difference, 2.07 points; 95% confidence interval, -0.27 to 4.41; p = 0.0819). The results of sensitivity analyses by ANCOVA with the last observation carried forward method for missing data indicated that the administration of Anyu Peibo capsules may lead to a significant reduction in depressive symptoms compared to the placebo (least-squares mean difference: 3.29 points; 95% confidence interval: 0.64-5.93; p = 0.0152). Furthermore, Anyu Peibo capsules showed significant benefits over placebo when the change in the HAMD-17 score from baseline to week 6 was evaluated as the secondary analysis (t = 2.01; 95% confidence interval, 0.03-4.23; p = 0.0464). Anyu Peibo capsules may have an effective and safe antidepressant effect, which warrants further research.

Prospective Associations between Childhood Exposure to Living with Adult Alcohol Misuse and Major Depressive Disorder in Adulthood: The Role of Child Maltreatment

Background Many children grow up with adult alcohol misuse in the home. A clearer understanding of this exposure’s long-term mental health consequences and the role of associated child maltreatment experiences and potential protective factors could guide relevant intervention strategies. Objective To prospectively evaluate the association between living with adult alcohol misuse during childhood and major depressive disorder (MDD) during adulthood; whether child maltreatment explains the association; and whether sex, school bonding, or neighborhood bonding moderate the association. Participants and setting: This study used longitudinal data from 783 individuals followed from childhood to age 39. Methods At grade 9, participants were asked whether they lived with adults who misused alcohol. Diagnostic assessments of MDD were conducted across three time-points during participants’ thirties and participants were categorized as having met diagnostic criteria 0, 1, or 2 or more times. Results Ordinal logistic regressions found that children living with adult alcohol misuse showed greater chronicity of adult MDD (OR = 1.63; 95% CI: 1.05, 2.52). There was a 49% reduction in the odds ratio and the association was no longer statistically significant when child maltreatment was included in the model (OR = 1.32; 95% CI: 0.84, 2.07). No statistically significant moderation of associations was observed. Conclusions Children exposed to adult alcohol misuse, and maltreatment often associated with this misuse, may be at risk for mental health challenges well into adulthood. Interventions that address childhood exposure to adult alcohol misuse and associated maltreatment may be important to mitigate long-term mental health challenges to exposed children.

Polygenic risk scores for schizophrenia and major depression are associated with socio-economic indicators of adversity in two British community samples

Schizophrenia (SCZ) and major depressive disorder (MDD) are complex psychiatric disorders which contribute substantially to the global burden of disease. Both psychopathologies are heritable with some genetic overlap between them. Importantly, SCZ and MDD have also been found to be associated with environmental risk factors. However, rather than being independent of genetic influences, exposure to environmental risk factors may be under genetic control, known as gene-environment correlation (rGE). In this study we investigated rGE in relation to polygenic risk scores for SCZ and MDD in adults, derived from large genome-wide association studies, across two different British community samples: Understanding Society (USoc) and the National Child Development Study (NCDS). We tested whether established environmental risk factors for SCZ and/or MDD are correlated with polygenic scores in adults and whether these associations differ between the two disorders and cohorts. Findings partially overlapped between disorders and cohorts. In NCDS, we identified a significant correlation between the genetic risk for MDD and an indicator of low socio-economic status, but no significant findings emerged for SCZ. In USoc, we replicated associations between indicators of low socio-economic status and the genetic propensity for MDD. In addition, we identified associations between the genetic susceptibility for SCZ and being single or divorced. Results across both studies provide further evidence that the genetic risk for SCZ and MDD were associated with common environmental risk factors, specifically MDD’s association with lower socio-economic status.

Dextromethorphan/Bupropion: First Approval.

An oral, fixed-dose combination of dextromethorphan hydrobromide [an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist] and the antidepressant bupropion hydrochloride (an aminoketone and CYP2D6 inhibitor that increases dextromethorphan bioavailability) [AUVELITYTM; dextromethorphan/bupropion], is being developed by Axsome Therapeutics, Inc. for the treatment of major depressive disorder (MDD), Alzheimer's disease agitation and smoking cessation. Dextromethorphan/bupropion was approved in the USA in August 2022 for the treatment of MDD in adults. This article summarizes the milestones in the development of dextromethorphan/bupropion leading to this first approval for the treatment of adults with MDD.

An Open-Label Rater-Blinded Randomized Trial of Vilazodone versus Escitalopram in Major Depression.

Vilazodone, a novel selective serotonin reuptake inhibitor and 5-HT1A partial agonist, was approved in 2011 for treatment for major depression. We aimed to compare the efficacy and safety of vilazodone versus escitalopram in patients with major depression at 4 weeks. Participants (n = 52) were adult major depressive disorder outpatients who were randomized to receive either oral escitalopram (modal endpoint dose 20 mg/day; n = 26) or oral vilazodone (modal endpoint dose 40 mg/day; n = 26). Rater-blinded assessments of depression scores (primary outcome) and clinical severity of illness (secondary outcome) were obtained at baseline, 2 weeks, and 4 weeks. Adverse effects such as weight gain, sexual dysfunction, and diarrhea were recorded at each visit. The primary analysis was performed on the Intention-to-treat sample. No significant difference was noted between groups on depression scores at study endpoint (F = 2.80, df = 1,50, P = 0.10); however, the vilazodone group had significantly lower endpoint clinical severity of illness (F = 7.69, df = 1,50, P = 0.01). At 2 weeks, there were no significant between-group differences on depression scores (F = 0.006, df = 1,50, P = 0.94). Instances of diarrhea (P = 0.001) were significantly higher in the vilazodone group. Clinical ratings of major depression did not differ significantly between vilazodone and escitalopram groups at the end of 4 weeks. Our findings are limited by lack of statistical power to detect smaller differences between groups, should they exist.

Prediction of remission among patients with a major depressive disorder based on the resting-state functional connectivity of emotion regulation networks

The prediction of antidepressant response is critical for psychiatrists to select the initial antidepressant drug for patients with major depressive disorders (MDD). The implicated brain networks supporting emotion regulation (ER) are critical in the pathophysiology of MDD and the prediction of antidepressant response. Therefore, the primary aim of the current study was to identify the neuroimaging biomarkers for the prediction of remission in patients with MDD based on the resting-state functional connectivity (rsFC) of the ER networks. A total of 81 unmedicated adult MDD patients were investigated and they underwent resting-state functional magnetic resonance imagining (fMRI) scans. The patients were treated with escitalopram for 12 weeks. The 17-item Hamilton depression rating scale was used for assessing remission. The 36 seed regions from predefined ER networks were selected and the rsFC matrix was caculated for each participant. The support vector machine algorithm was employed to construct prediction model, which separated the patients with remission from those with non-remission. And leave-one-out cross-validation and the area under the curve (AUC) of the receiver operating characteristic were used for evaluating the performance of the model. The accuracy of the prediction model was 82.08% (sensitivity = 71.43%, specificity = 89.74%, AUC = 0.86). The rsFC between the left medial superior frontal gyrus and the right inferior frontal gyrus as well as the precuneus were the features with the highest discrimination ability in predicting remission from escitalopram among the MDD patients. Results from our study demonstrated that rsFC of the ER brain networks are potential predictors for the response of antidepressant drugs. The trial name: appropriate technology study of MDD diagnosis and treatment based on objective indicators and measurement. URL: http://www.chictr.org.cn/showproj.aspx?proj=21377. Registration number: ChiCTR-OOC-17012566.

The Clinical Effectiveness of Blended Cognitive Behavioral Therapy Compared With Face-to-Face Cognitive Behavioral Therapy for Adult Depression: Randomized Controlled Noninferiority Trial

BackgroundInternet-based cognitive behavioral therapy (iCBT) has been demonstrated to be cost- and clinically effective. There is a need, however, for increased therapist contact for some patient groups. Combining iCBT with traditional face-to-face (FtF) consultations in a blended format may produce a new treatment format (B-CBT) with multiple benefits from both traditional CBT and iCBT, such as individual adaptation, lower costs than traditional therapy, wide geographical and temporal availability, and possibly lower threshold to implementation.ObjectiveThe primary aim of this study is to compare directly the clinical effectiveness of B-CBT with FtF-CBT for adult major depressive disorder.MethodsA 2-arm randomized controlled noninferiority trial compared B-CBT for adult depression with treatment as usual (TAU). The trial was researcher blinded (unblinded for participants and clinicians). B-CBT comprised 6 sessions of FtF-CBT alternated with 6-8 web-based CBT self-help modules. TAU comprised 12 sessions of FtF-CBT. All participants were aged 18 or older and met the diagnostic criteria for major depressive disorder and were recruited via a national iCBT clinic. The primary outcome was change in depression severity on the 9-item Patient Health Questionnaire (PHQ-9). Secondary analyses included client satisfaction (8-item Client Satisfaction Questionnaire [CSQ-8]), patient expectancy (Credibility and Expectancy Questionnaire [CEQ]), and working (Working Alliance Inventory [WAI] and Technical Alliance Inventory [TAI]). The primary outcome was analyzed by a mixed effects model including all available data from baseline, weekly measures, 3-, 6, and 12-month follow-up.ResultsA total of 76 individuals were randomized, with 38 allocated to each treatment group. Age ranged from 18 to 71 years (SD 13.96) with 56 (74%) females. Attrition rate was 20% (n=15), which was less in the FtF-CBT group (n=6, 16%) than in the B-CBT group (n=9, 24%). As many as 53 (70%) completed 9 or more sessions almost equally distributed between the groups (nFtF-CBT=27, 71%; nB-CBT=26, 68%). PHQ-9 reduced 11.38 points in the FtF-CBT group and 8.10 in the B-CBT group. At 6 months, the mean difference was a mere 0.17 points. The primary analyses confirmed large and significant within-group reductions in both groups (FtF-CBT: β=–.03; standard error [SE] 0.00; P<.001 and B-CBT: β=–.02; SE 0.00; P<.001). A small but significant interaction effect was observed between groups (β=.01; SE 0.00; P=.03). Employment status influenced the outcome differently between groups, where the B-CBT group was seen to profit more from not being full-time employed than the FtF group.ConclusionsWith large within-group effects in both treatment arms, the study demonstrated feasibility of B-CBT in Denmark. At 6 months’ follow-up, there appeared to be no difference between the 2 treatment formats, with a small but nonsignificant difference at 12 months. The study seems to demonstrate that B-CBT is capable of producing treatment effects that are close to FtF-CBT and that completion rates and satisfaction rates were comparable between groups. However, the study was limited by small sample size and should be interpreted with caution.Trial RegistrationClinicalTrials.gov NCT02796573; https://clinicaltrials.gov/ct2/show/NCT02796573International Registered Report Identifier (IRRID)RR2-10.1186/s12888-016-1140-y

Men's Depression, Externalizing, and DSM-5-TR: Primary Signs and Symptoms or Co-occurring Symptoms?

Men's Depression, Externalizing, and DSM-5-TR: Primary Signs and Symptoms or Co-occurring Symptoms?