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Translational Psychiatry Jun 2023Major depressive disorder (MDD) is a very prevalent mental disorder that imposes an enormous burden on individuals, society, and health care systems. Most patients... (Review)
Review
Major depressive disorder (MDD) is a very prevalent mental disorder that imposes an enormous burden on individuals, society, and health care systems. Most patients benefit from commonly used treatment methods such as pharmacotherapy, psychotherapy, electroconvulsive therapy (ECT), and repetitive transcranial magnetic stimulation (rTMS). However, the clinical decision on which treatment method to use remains generally informed and the individual clinical response is difficult to predict. Most likely, a combination of neural variability and heterogeneity in MDD still impedes a full understanding of the disorder, as well as influences treatment success in many cases. With the help of neuroimaging methods like functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), the brain can be understood as a modular set of functional and structural networks. In recent years, many studies have investigated baseline connectivity biomarkers of treatment response and the connectivity changes after successful treatment. Here, we systematically review the literature and summarize findings from longitudinal interventional studies investigating the functional and structural connectivity in MDD. By compiling and discussing these findings, we recommend the scientific and clinical community to deepen the systematization of findings to pave the way for future systems neuroscience roadmaps that include brain connectivity parameters as a possible precision component of the clinical evaluation and therapeutic decision.
Topics: Humans; Depressive Disorder, Major; Diffusion Tensor Imaging; Brain; Electroconvulsive Therapy; Transcranial Magnetic Stimulation; Magnetic Resonance Imaging
PubMed: 37296121
DOI: 10.1038/s41398-023-02499-y -
Clinical Pharmacology and Therapeutics Dec 2022Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15-1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13-1.88) and 1.26 (95% CI = 0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.
Topics: Adult; Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Pharmacogenomic Testing; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 36111494
DOI: 10.1002/cpt.2748 -
Clinical Psychology Review Apr 2021There has been a marked increase of network studies of Major Depressive Disorder (MDD). Despite rapidly growing contributions, their findings have yet to be... (Review)
Review
There has been a marked increase of network studies of Major Depressive Disorder (MDD). Despite rapidly growing contributions, their findings have yet to be systematically aggregated and examined. We therefore conducted a systematic review of depression network studies using PRISMA guidelines. A total of 254 clinical and population studies were collected from ISI's Web of Science and PsycINFO, between January 2010 to May 2020. A total of 23 between-subject studies were included for review, resulting in 58 cross-sectional networks. To determine their most critical symptoms and their connections, we analyzed strength centrality rankings, and aggregated the most robust symptoms connections into a summary network. Results indicated substantial variability between study samples, depression measures, and network features. Fatigue and Depressed Mood were the most central symptoms, while Weight changes tended to have the weakest centrality. Depressed Mood and Fatigue formed two separated symptoms communities characterized by recurrent connections, with Mood-Anhedonia as the most frequent edge of MDD. Network analysis informed our understanding of MDD, suggesting the critical role of Fatigue and Depressed Mood. The study's findings are discussed in their clinical and methodological implications, including future directions for network studies of MDD.
Topics: Affect; Anhedonia; Cross-Sectional Studies; Depressive Disorder, Major; Humans
PubMed: 33721606
DOI: 10.1016/j.cpr.2021.102000 -
Journal of Affective Disorders May 2024Overlapping but divided literatures suggest certain depression facets may pose greater obesity and diabetes risk than others. Our objectives were to integrate the major... (Review)
Review
BACKGROUND
Overlapping but divided literatures suggest certain depression facets may pose greater obesity and diabetes risk than others. Our objectives were to integrate the major depressive disorder (MDD) subtype and depressive symptom cluster literatures and to clarify which facets are associated with the greatest cardiometabolic disease risk.
METHODS
We conducted a systematic review of published studies examining associations of ≥2 MDD subtypes or symptom clusters with obesity or diabetes risk outcomes. We report which facets the literature is "in favor" of (i.e., having the strongest or most consistent results).
RESULTS
Forty-five articles were included. Of the MDD subtype-obesity risk studies, 14 were in favor of atypical MDD, and 8 showed similar or null associations across subtypes. Of the symptom cluster-obesity risk studies, 5 were in favor of the somatic cluster, 1 was in favor of other clusters, and 5 were similar or null. Of the MDD subtype-diabetes risk studies, 7 were in favor of atypical MDD, 3 were in favor of other subtypes, and 5 were similar or null. Of the symptom cluster-diabetes risk studies, 7 were in favor of the somatic cluster, and 5 were similar or null.
LIMITATIONS
Limitations in study design, sample selection, variable measurement, and analytic approach in these literatures apply to this review.
CONCLUSIONS
Atypical MDD and the somatic cluster are most consistently associated with obesity and diabetes risk. Future research is needed to establish directionality and causality. Identifying the depression facets conferring the greatest risk could improve cardiometabolic disease risk stratification and prevention programs.
Topics: Humans; Depressive Disorder, Major; Depression; Syndrome; Obesity; Diabetes Mellitus; Cardiovascular Diseases
PubMed: 38432462
DOI: 10.1016/j.jad.2024.02.051 -
Acta Neuropsychiatrica Feb 2023A better understanding of the genetic, molecular and cellular mechanisms of brain-derived neurotrophic factor (BDNF) and its association with neuroplasticity could play... (Review)
Review
OBJECTIVE
A better understanding of the genetic, molecular and cellular mechanisms of brain-derived neurotrophic factor (BDNF) and its association with neuroplasticity could play a pivotal role in finding future therapeutic targets for novel drugs in major depressive disorder (MDD). Because there are conflicting results regarding the exact role of BDNF polymorphisms in MDD still, we set out to systematically review the current evidence regarding BDNF-related mutations in MDD.
METHODS
We conducted a keyword-guided search of the PubMed and Embase databases, using 'BDNF' or 'brain-derived neurotrophic factor' and 'major depressive disorder' and 'single-nucleotide polymorphism'. We included all publications in line with our exclusion and inclusion criteria that focused on BDNF-related mutations in the context of MDD.
RESULTS
Our search yielded 427 records in total. After screening and application of our eligibility criteria, 71 studies were included in final analysis. According to present overall scientific data, there is a possibly major pathophysiological role for BDNF neurotrophic systems to play in MDD. However, on the one hand, the synthesis of evidence makes clear that likely no overall association of BDNF-related mutations with MDD exists. On the other hand, it can be appreciated that solidifying evidence emerged on specific significant sub-conditions and stratifications based on various demographic, clinico-phenotypical and neuromorphological variables.
CONCLUSIONS
Further research should elucidate specific BDNF-MDD associations based on demographic, clinico-phenotypical and neuromorphological variables. Furthermore, biomarker approaches, specifically combinatory ones, involving BDNF should be further investigated.
Topics: Humans; Depressive Disorder, Major; Mutation; Biomarkers; Polymorphism, Single Nucleotide
PubMed: 35993165
DOI: 10.1017/neu.2022.22 -
Journal of Affective Disorders Jul 2023Major Depressive Disorder (MDD) and obesity are bidirectionally related, but the amount of weight-gain secondary to MDD is unknown. We aimed to estimate the adjusted... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Major Depressive Disorder (MDD) and obesity are bidirectionally related, but the amount of weight-gain secondary to MDD is unknown. We aimed to estimate the adjusted effect of MDD on weight-change in prospective studies compared to individuals without MDD.
METHODS
Scopus/MEDLINE, PsycInfo, Web of Science and Cochrane were systematically searched for prospective observational studies of participants with a diagnosis of MDD. We included studies that conducted regression analyses on weight-variables. We searched for weight-variables reported at baseline, follow-up, and regression analyses. A meta-analysis of the odds ratios reported in logistic regression models was performed using the generic inverse weight variance method.
RESULTS
Eight studies were included with a total of 60,443 subjects; 56.8 % with MDD. Weight-variables included weight, BMI, waist circumference, fat mass, and obesity incidence. In three follow-up reports, weight-variables increased more in participants with MDD and its subphenotypes than in control subjects, except for one MDD subphenotype. Meta-analysis of three eligible studies (n = 21,935) showed a significantly greater likelihood of incident obesity in participants with MDD (OR:1.48, 95%CI 1.03-2.13). MDD subphenotype reports might suggest a greater risk for atypical MDD.
LIMITATIONS
Heterogeneity in weight related variables, follow-ups, and regression models; scarcity of follow-up data; and limited studies eligible for meta-analysis.
CONCLUSIONS
Despite previous associations between MDD and obesity, current prospective evidence on MDD related weight-change is scarce and heterogeneous. Our findings suggest a need to standardize weight-change assessment in MDD trials. Moreover, careful weight tracking and management should be incorporated in clinical settings. PROSPERO registration CRD42020214427.
Topics: Adult; Humans; Depressive Disorder, Major; Prospective Studies; Obesity; Weight Gain; Observational Studies as Topic
PubMed: 36963517
DOI: 10.1016/j.jad.2023.03.050 -
Psychological Medicine Jul 2023Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy.
METHODS
A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events.
RESULTS
Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13, = 4375), amisulpride [1.99 (1.55-2.55)], sulpiride [1.50 (1.03-2.17)], and quetiapine [1.48 (1.23-1.78)] were significantly superior to placebo regarding treatment response. However, intolerability-related discontinuations were significantly higher compared to placebo with amisulpride and quetiapine. In adjunctive therapy (studies = 32, = 8349), ziprasidone [1.80 (1.07-3.04)], risperidone [1.59 (1.19-2.14)], aripiprazole [1.54 (1.35-1.76)], brexpiprazole [1.41 (1.21-1.66)], cariprazine [1.27 (1.07-1.52)], and quetiapine [1.23 (1.08-1.41)] were significantly superior to placebo regarding treatment response. However, of these antipsychotics that were superior to placebo, only risperidone was equivalent to placebo regarding discontinuation due to intolerability, while the other antipsychotics were inferior.
CONCLUSION
Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Risperidone; Depressive Disorder, Major; Amisulpride; Olanzapine; Benzodiazepines; Dibenzothiazepines
PubMed: 35510505
DOI: 10.1017/S0033291722000745 -
Journal of Affective Disorders Apr 2020Comorbidity between Substance Use Disorders (SUDs) and major depression is highly prevalent. This systematic review and meta-analysis aimed to estimate the prevalence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Comorbidity between Substance Use Disorders (SUDs) and major depression is highly prevalent. This systematic review and meta-analysis aimed to estimate the prevalence of SUDs in subjects diagnosed with a major depressive disorder (MDD) in community, inpatient and outpatient settings.
METHODS
A comprehensive literature search of Medline, EMBASE, PsycINFO and CINAHL databases was conducted from 1990 to 2019. Prevalence of co-morbid SUDs and MDD were extracted and odds ratios (ORs) were calculated using random effects meta-analysis.
RESULTS
There were 48 articles identified by electronic searches with a total sample size of 348,550 subjects that yielded 14 unique epidemiological studies, 2 national case registry studies, 7 large cohort studies and 20 clinical studies using in- or out-patients. The prevalence of any SUD in individuals with MDD was 0.250. Maximum prevalence was found with alcohol use disorder (0.208), followed by illicit drug use disorder (0.118) and cannabis use disorder (0.117). Meta-analysis showed the pooled variance of any AUD in men with MDD was 36%, which was significantly higher than that for females with MDD (19%, OR 2.628 95% CI 2.502, 2.760).
CONCLUSIONS
Few studies were published over the last decade so current prevalence rates of SUD in MDD are needed. Meta-analysis revealed that SUDs in MDD are highly prevalent and rates have not changed over time. The persistently high prevalence suggests there is an urgent need for more informative studies to help develop better prevention and treatment options for reducing prevalence of SUDs in persons with major depression and co-morbid disorders.
Topics: Alcoholism; Comorbidity; Depressive Disorder, Major; Female; Humans; Male; Prevalence; Substance-Related Disorders
PubMed: 32056890
DOI: 10.1016/j.jad.2020.01.141 -
Journal of Affective Disorders Aug 2023Although reduced heart rate variability (HRV) has been observed in adults with major depressive disorder (MDD), the correlation between HRV and MDD in children and... (Meta-Analysis)
Meta-Analysis Review
Although reduced heart rate variability (HRV) has been observed in adults with major depressive disorder (MDD), the correlation between HRV and MDD in children and adolescents remains uncertain and requires to be systematically reviewed. Our meta-analysis included ten articles comprising 410 MDD patients and 409 healthy controls. Adolescents with MDD showed significant reductions in most HRV measures, such as HF-HRV, RMSSD, and PNN50, and depressive symptom severity was statistically associated with RMSSD, HF-HRV, and LF/HF ratio. A large heterogeneity across studies was detected. Sensitivity analysis revealed that removal of a specific study would significantly decline the heterogeneity for measures of HF-HRV, LF-HRV, and SDNN, and meta-regression analysis found that sample size and year of publication substantially moderated the differences between depressed samples and controls in RMSSD. Compared with adults, depression-induced autonomic dysfunction was more detectable in children and adolescents with substantial effects. Moreover, excluded studies which reported both HRV and MDD or depression symptoms were summarized based on objectives. Findings indicate that it is promising for HRV to be an appropriate and objective candidate biomarker for clinically depressed children and adolescents.
Topics: Adult; Humans; Adolescent; Child; Depressive Disorder, Major; Heart Rate; Regression Analysis
PubMed: 37178829
DOI: 10.1016/j.jad.2023.05.022 -
The International Journal of... Jun 2023Major depressive disorder (MDD) is a highly prevalent and burdensome condition. This study aims to evaluate the effectiveness, tolerability, and safety of vortioxetine... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Major depressive disorder (MDD) is a highly prevalent and burdensome condition. This study aims to evaluate the effectiveness, tolerability, and safety of vortioxetine in treating MDD based on real-world data.
METHODS
A systematic search of 8 electronic databases was performed from inception until October 2022 to identify real-world studies, excluding randomized controlled trials. We conducted subgroup, meta-regression, sensitivity analyses, publication bias, and quality assessments using the random-effects model. The effects were summarized by rates or standardized mean difference (SMD) with 95% confidence interval (CI).
RESULTS
Of the 870 records identified, 11 studies (3139 participants) and 10 case reports or series were eligible for inclusion. Vortioxetine significantly relieved depression symptoms as assessed by both patients (SMD = 2.25, 95% CI = 1.60-2.89) and physicians (SMD = 3.73, 95% CI = 2.78-4.69). Cognitive function (SMD =1.86, 95% CI = 1.11-2.62) and functional disability (SMD =1.71, 95% CI = 1.14-2.29) were similarly markedly improved. Subgroup and meta-regression analyses showed that geographic location and medication regimen (whether combined with other antidepressants) were crucial factors influencing effectiveness (in terms of depression severity and cognitive function), potentially contributing to significant heterogeneity. The estimated response and remission rates were 66.4% (95% CI = 51.2%-81.5%) and 58.0% (95% CI = 48.9%-67.1%), respectively. Vortioxetine was well tolerated, with a pooled dropout rate of 3.5% (95% CI = 1.8%-5.8%), and the most common adverse event was nausea, with an estimated rate of 8.9% (95% CI = 3.8%-15.8%).
LIMITATIONS
The study has some limitations, including significant heterogeneity and limited evidence for some outcomes.
CONCLUSIONS
Vortioxetine is effective, well tolerated, and safe for treating MDD in clinical practice, with significant improvements observed in depressive severity, cognitive function, and functioning. Future studies should directly compare vortioxetine with other antidepressants in real-world settings to further evaluate its clinical utility.
Topics: Humans; Vortioxetine; Depressive Disorder, Major; Antidepressive Agents; Nausea; Cognition
PubMed: 37105713
DOI: 10.1093/ijnp/pyad018