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Association Between Physical Activity and Risk of Depression: A Systematic Review and Meta-analysis.JAMA Psychiatry Jun 2022Depression is the leading cause of mental health-related disease burden and may be reduced by physical activity, but the dose-response relationship between activity and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Depression is the leading cause of mental health-related disease burden and may be reduced by physical activity, but the dose-response relationship between activity and depression is uncertain.
OBJECTIVE
To systematically review and meta-analyze the dose-response association between physical activity and incident depression from published prospective studies of adults.
DATA SOURCES
PubMed, SCOPUS, Web of Science, PsycINFO, and the reference lists of systematic reviews retrieved by a systematic search up to December 11, 2020, with no language limits. The date of the search was November 12, 2020.
STUDY SELECTION
We included prospective cohort studies reporting physical activity at 3 or more exposure levels and risk estimates for depression with 3000 or more adults and 3 years or longer of follow-up.
DATA EXTRACTION AND SYNTHESIS
Data extraction was completed independently by 2 extractors and cross-checked for errors. A 2-stage random-effects dose-response meta-analysis was used to synthesize data. Study-specific associations were estimated using generalized least-squares regression and the pooled association was estimated by combining the study-specific coefficients using restricted maximum likelihood.
MAIN OUTCOMES AND MEASURES
The outcome of interest was depression, including (1) presence of major depressive disorder indicated by self-report of physician diagnosis, registry data, or diagnostic interviews and (2) elevated depressive symptoms established using validated cutoffs for a depressive screening instrument.
RESULTS
Fifteen studies comprising 191 130 participants and 2 110 588 person-years were included. An inverse curvilinear dose-response association between physical activity and depression was observed, with steeper association gradients at lower activity volumes; heterogeneity was large and significant (I2 = 74%; P < .001). Relative to adults not reporting any activity, those accumulating half the recommended volume of physical activity (4.4 marginal metabolic equivalent task hours per week [mMET-h/wk]) had 18% (95% CI, 13%-23%) lower risk of depression. Adults accumulating the recommended volume of 8.8 mMET hours per week had 25% (95% CI, 18%-32%) lower risk with diminishing potential benefits and higher uncertainty observed beyond that exposure level. There were diminishing additional potential benefits and greater uncertainty at higher volumes of physical activity. Based on an estimate of exposure prevalences among included cohorts, if less active adults had achieved the current physical activity recommendations, 11.5% (95% CI, 7.7%-15.4%) of depression cases could have been prevented.
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis of associations between physical activity and depression suggests significant mental health benefits from being physically active, even at levels below the public health recommendations. Health practitioners should therefore encourage any increase in physical activity to improve mental health.
Topics: Adult; Depression; Depressive Disorder, Major; Exercise; Humans; Prospective Studies
PubMed: 35416941
DOI: 10.1001/jamapsychiatry.2022.0609 -
The British Journal of Clinical... Jun 2022Adolescence is a formative and turbulent phase where physiological, psychosocial, and cognitive changes leave adolescents vulnerable to psychological disorders. Given... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Adolescence is a formative and turbulent phase where physiological, psychosocial, and cognitive changes leave adolescents vulnerable to psychological disorders. Given the lack of reviews that consolidate and compare worldwide prevalence of depression among adolescents, this review aims to examine the global prevalence of major depressive disorders, dysthymia, and elevated depressive symptoms among adolescents.
METHODS
A systematic review and meta-analysis was conducted. Six databases were searched for studies published from 2001 to December 2020. Seventy-two studies were included. Subgroup analysis were performed for year of publication, geographical region, gender, and assessment tools used.
RESULTS
The global point prevalence rate of elevated self-reported depressive symptoms from 2001 to 2020 was 34% (95% CI: 0.30-0.38). Point prevalence for major depressive disorder (MDD) and dysthymia was 8% (95% CI: 0.02-0.13) and 4% (95% CI: 0.01-0.07), respectively. The pooled one-year prevalence and lifetime prevalence for MDD were 8% (95% CI: 0.05-0.12) and 19% (95% CI: 0.12-0.26). Point prevalence of elevated depressive symptoms among adolescents increased from 24% (95% CI: 0.19-0.28) between 2001 and 2010 to 37% (95% CI: 0.32-0.42) between 2011 and 2020. The Middle East, Africa, and Asia have the highest prevalence of elevated depressive symptoms, and female adolescents were reported to have a higher prevalence of elevated depressive symptoms than male adolescents.
CONCLUSION
Besides targeting those with existing clinical depression, research and policies should also focus on educational and supportive mitigation efforts to curb depressive symptoms among adolescents before escalation. The findings encourage future research to develop more gender-specific and culturally relevant intervention programmes.
PRACTITIONER POINTS
34% of adolescents globally, aged 10-19 years, are at risk of developing clinical depression, which exceeds the reported estimates of individuals aged 18 to 25 years. Practitioners are highly encouraged to prioritize depression screening and intervention implementation for individuals in this age group. Female adolescents and adolescents from Middle East, Africa, and Asia have the highest risk of developing depression. This urges practitioners and researchers to develop more gender-specific and culturally relevant intervention programmes.
Topics: Adolescent; Depression; Depressive Disorder, Major; Female; Humans; Male; Prevalence
PubMed: 34569066
DOI: 10.1111/bjc.12333 -
The Lancet. Psychiatry Jul 2020Depressive disorders are common in children and adolescents. Antidepressants, psychotherapies, and their combination are often used in routine clinical practice;... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis.
BACKGROUND
Depressive disorders are common in children and adolescents. Antidepressants, psychotherapies, and their combination are often used in routine clinical practice; however, available evidence on the comparative efficacy and safety of these interventions is inconclusive. Therefore, we sought to compare and rank all available treatment interventions for the acute treatment of depressive disorders in children and adolescents.
METHODS
We did a systematic review and network meta-analysis. We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, PsycINFO, ProQuest, CINAHL, LiLACS, international trial registries, and the websites of regulatory agencies for published and unpublished randomised controlled trials from database inception until Jan 1, 2019. We included placebo-controlled and head-to-head trials of 16 antidepressants, seven psychotherapies, and five combinations of antidepressant and psychotherapy that are used for the acute treatment of children and adolescents (≤18 years old and of both sexes) with depressive disorder diagnosed according to standard operationalised criteria. Trials recruiting participants with treatment-resistant depression, bipolar disorder, psychotic depression, treatment duration of less than 4 weeks, or an overall sample size of fewer than ten patients were excluded. We extracted data following a predefined hierarchy of outcome measures, and assessed risk of bias and certainty of evidence using validated methods. Primary outcomes were efficacy (change in depressive symptoms) and acceptability (treatment discontinuation due to any cause). We estimated summary standardised mean differences (SMDs) or odds ratios (ORs) with credible intervals (CrIs) using network meta-analysis with random effects. This study was registered with PROSPERO, number CRD42015020841.
FINDINGS
From 20 366 publications, we included 71 trials (9510 participants). Depressive disorders in most studies were moderate to severe. In terms of efficacy, fluoxetine plus cognitive behavioural therapy (CBT) was more effective than CBT alone (-0·78, 95% CrI -1·55 to -0·01) and psychodynamic therapy (-1·14, -2·20 to -0·08), but not more effective than fluoxetine alone (-0·22, -0·86 to 0·42). No pharmacotherapy alone was more effective than psychotherapy alone. Only fluoxetine plus CBT and fluoxetine were significantly more effective than pill placebo or psychological controls (SMDs ranged from -1·73 to -0·51); and only interpersonal therapy was more effective than all psychological controls (-1·37 to -0·66). Nortriptyline (SMDs ranged from 1·04 to 2·22) and waiting list (SMDs ranged from 0·67 to 2·08) were less effective than most active interventions. In terms of acceptability, nefazodone and fluoxetine were associated with fewer dropouts than sertraline, imipramine, and desipramine (ORs ranged from 0·17 to 0·50); imipramine was associated with more dropouts than pill placebo, desvenlafaxine, fluoxetine plus CBT, and vilazodone (2·51 to 5·06). Most of the results were rated as "low" to "very low" in terms of confidence of evidence according to Confidence In Network Meta-Analysis.
INTERPRETATION
Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents. However, the effects of these interventions might vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis.
FUNDING
National Key Research and Development Program of China.
Topics: Adolescent; Antidepressive Agents; Child; Depressive Disorder; Evidence-Based Medicine; Humans; Network Meta-Analysis; Psychotherapy; Randomized Controlled Trials as Topic
PubMed: 32563306
DOI: 10.1016/S2215-0366(20)30137-1 -
Journal of Affective Disorders Apr 2022To compare the efficacy and discontinuation of augmentation agents in adult patients with treatment-resistant depression (TRD). We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the efficacy and discontinuation of augmentation agents in adult patients with treatment-resistant depression (TRD). We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of augmentation agents.
METHODS
We included randomized controlled trials comparing one active drug with another or with placebo following a treatment course up to 24 weeks. Nineteen agents were included: stimulants, atypical antipsychotics, thyroid hormones, antidepressants, and mood stabilizers. Data for response/remission and all-cause discontinuation rates were analyzed. We estimated effect-size by relative risk using pairwise and NMA with random-effects model.
RESULTS
A total of 65 studies (N = 12,415) with 19 augmentation agents were included in the NMA. Our findings from the NMA for response rates, compared to placebo, were significant for: liothyronine, nortriptyline, aripiprazole, brexpiprazole, quetiapine, lithium, modafinil, olanzapine (fluoxetine), cariprazine, and lisdexamfetamine. For remission rates, compared to placebo, were significant for: thyroid hormone(T4), aripiprazole, brexpiprazole, risperidone, quetiapine, and olanzapine (fluoxetine). Compared to placebo, ziprasidone, mirtazapine, and cariprazine had statistically significant higher discontinuation rates. Overall, 24% studies were rated as having low risk of bias (RoB), 63% had moderate RoB and 13% had high RoB.
LIMITATIONS
Heterogeneity in TRD definitions, variable trial duration and methodological clinical design of older studies and small number of trials per comparisons.
CONCLUSIONS
This NMA suggests a superiority of the regulatory approved adjunctive atypical antipsychotics, thyroid hormones, dopamine compounds (modafinil and lisdexamfetamine) and lithium. Acceptability was lower with ziprasidone, mirtazapine, and cariprazine. Further research and head-to-head studies should be considered to strengthen the best available options for TRD.
Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Depression; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Humans; Network Meta-Analysis
PubMed: 34986373
DOI: 10.1016/j.jad.2021.12.134 -
Neuroscience and Biobehavioral Reviews Jul 2019With growing interest in the gut microbiome, prebiotics and probiotics have received considerable attention as potential treatments for depression and anxiety. We... (Meta-Analysis)
Meta-Analysis
With growing interest in the gut microbiome, prebiotics and probiotics have received considerable attention as potential treatments for depression and anxiety. We conducted a random-effects meta-analysis of 34 controlled clinical trials evaluating the effects of prebiotics and probiotics on depression and anxiety. Prebiotics did not differ from placebo for depression (d = -.08, p = .51) or anxiety (d = .12, p = .11). Probiotics yielded small but significant effects for depression (d = -.24, p < .01) and anxiety (d = -.10, p = .03). Sample type was a moderator for probiotics and depression, with a larger effect observed for clinical/medical samples (d = -.45, p < .001) than community ones. This effect increased to medium-to-large in a preliminary analysis restricted to psychiatric samples (d = -.73, p < .001). There is general support for antidepressant and anxiolytic effects of probiotics, but the pooled effects were reduced by the paucity of trials with clinical samples. Additional randomized clinical trials with psychiatric samples are necessary fully to evaluate their therapeutic potential.
Topics: Anxiety Disorders; Controlled Clinical Trials as Topic; Depressive Disorder; Gastrointestinal Microbiome; Humans; Prebiotics; Probiotics
PubMed: 31004628
DOI: 10.1016/j.neubiorev.2019.03.023 -
Neuroscience and Biobehavioral Reviews Jul 2019Environmental stressors, such as childhood maltreatment, have been recognized to contribute to the development of depression. Growing evidence suggests that epigenetic...
Environmental stressors, such as childhood maltreatment, have been recognized to contribute to the development of depression. Growing evidence suggests that epigenetic changes are a key mechanism by which stressors interact with the genome leading to stable changes in DNA structure, gene expression, and behaviour. The current review aimed to evaluate the relationship between stress-associated epigenetic changes and depression. Human studies were identified via systematic searching of PubMed/Medline from inception to February 2018. Seventeen articles were identified. Stress-associated epigenetic changes in the following genes were correlated with depression: NRC31, SLCA4, BDNF, FKBP5, SKA2, OXTR, LINGO3, POU3F1 and ITGB1. Epigenetic changes in glucocorticoid signaling (e.g., NR3C1, FKBP5), serotonergic signaling (e.g. SLC6A4), and neurotrophin (e.g., BDNF) genes appear to be the most promising therapeutic targets for future research. However, continued research is warranted due to inconsistent findings regarding the directionality of epigenetic modification. Future studies should also aim to control for the use of psychotropic agents due to their widespread use in depressed populations and established effects on DNA methylation.
Topics: Adult; Adverse Childhood Experiences; Child; Child Abuse; Depression; Depressive Disorder, Major; Epigenesis, Genetic; Humans; Stress, Psychological
PubMed: 31005627
DOI: 10.1016/j.neubiorev.2019.04.010 -
Neuroscience and Biobehavioral Reviews Jan 2022Major depressive disorder is characterized by a depressed mood or feeling of sadness, loss of interest or pleasure in everyday activities. Depressed individuals have a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Major depressive disorder is characterized by a depressed mood or feeling of sadness, loss of interest or pleasure in everyday activities. Depressed individuals have a cognitive impairment, low self-esteem, difficulty making decisions, feeling helpless and hopeless. The factors that have been associated with depression include the lack of social support, living in rural areas, suffering from chronic diseases, smoking, and alcohol abuse. This study aimed to investigate the global prevalence of major depressive disorder in the elderly.
METHOD
The electronic database such as Web of Science (WoS), Scopus, SID, PubMed, Google Scholar, Mag Iran, and IranDoc were systematically searched for studies reporting the prevalence of major depressive disorderin the elderly published up to March 2021. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) software. Heterogeneity between the studies was evaluated using the I index. Begg and Mazumdar rank correlation test was used to assess publication bias.
RESULT
A total of 20 studies involving 18953 participants were included in this study. The global prevalence of major depression in the elderly was 13.3 % (95 % CI: 8.4-20.3 %). In the subgroup analysis, the prevalence of major depression in elderly women was 11.9 % (95 % CI: 7.6-18.6) and men 9.7 % (95 % CI: 5.2-17.3). No comparison was made between the two sexes, but based on the confidence intervals and large overlap, the two groups are not statistically different. Among continents, Australia had the highest prevalence of major depression in the elderly at 20.1 % (CI: 14.5-27.2 %). This was followed by Europe at 12.9 % (95 % CI: 5.1-28.9 %).
CONCLUSION
Major depressive disorder has a growing trend in the elderly population of the world. The prevalence of major depression in the elderly depends on various clinical and demographic factors such as age and gender. Therefore, mental health and the quality of life (QoL) of the elderly are important. The present study emphasizes the importance of social support in mental health that can reduce depression in the elderly.
Topics: Aged; Depressive Disorder, Major; Europe; Female; Humans; Male; Prevalence; Quality of Life
PubMed: 34742925
DOI: 10.1016/j.neubiorev.2021.10.041 -
Journal of Affective Disorders Apr 2020Growing attention has been paid to the field of gut microbiota for mental disorders over the last decade. However, to our knowledge, no studies have conducted systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Growing attention has been paid to the field of gut microbiota for mental disorders over the last decade. However, to our knowledge, no studies have conducted systematic reviews on the association between gut microbiota and major depressive disorder (MDD) in both interventional and non-interventional studies.
METHODS
We conducted a systematic review and meta-analysis of 16 studies (10 observational [701 participants] and six interventional trials [302 participants]) examining gut microbiota in patients with MDD. The primary outcome measures were differences in the profile of microbiota in the observational studies, and symptom changes for depression between pre- and post-intervention with probiotics in the interventional trials.
RESULTS
In the observational studies, significant reductions in several taxa at the family and genus levels were observed in patients with MDD compared to non-depressed controls. In the interventional studies with probiotics, a significant improvement was found in depressive symptomatology compared to controls (SMD = -1.62, 95% CI = -2.73 to -0.51, p< 0.01).
LIMITATIONS
Lack of consideration of the effects of diet and pharmacotherapy was a possible limitation.
CONCLUSIONS
Our results indicate that several taxa at the family and genus levels, specifically family Prevotellaceae, genus Corprococcus, and Faecalibacterium, were decreased in MDD compared to non-depressed controls in observational studies, and depressive symptoms were improved compared to controls in interventional studies with probiotics. Due to the limited number of studies, further studies considering diet and pharmacotherapy are needed to explore the relationships between gut microbiota and MDD in humans.
Topics: Depressive Disorder, Major; Diet; Gastrointestinal Microbiome; Humans; Microbiota; Probiotics
PubMed: 32056863
DOI: 10.1016/j.jad.2020.01.102 -
Molecular Psychiatry Feb 2020Leading biological hypotheses propose that biological changes may underlie major depressive disorder onset and relapse/recurrence. Here, we investigate if there is... (Meta-Analysis)
Meta-Analysis
Leading biological hypotheses propose that biological changes may underlie major depressive disorder onset and relapse/recurrence. Here, we investigate if there is prospective evidence for biomarkers derived from leading theories. We focus on neuroimaging, gastrointestinal factors, immunology, neurotrophic factors, neurotransmitters, hormones, and oxidative stress. Searches were performed in Pubmed, Embase and PsychInfo for articles published up to 06/2019. References and citations of included articles were screened to identify additional articles. Inclusion criteria were having an MDD diagnosis as outcome, a biomarker as predictor, and prospective design search terms were formulated accordingly. PRISMA guidelines were applied. Meta-analyses were performed using a random effect model when three or more comparable studies were identified, using a random effect model. Our search resulted in 67,464 articles, of which 75 prospective articles were identified on: Neuroimaging (N = 24), Gastrointestinal factors (N = 1), Immunology (N = 8), Neurotrophic (N = 2), Neurotransmitters (N = 1), Hormones (N = 39), Oxidative stress (N = 1). Meta-analyses on brain volumes and immunology markers were not significant. Only cortisol (N = 19, OR = 1.294, p = 0.024) showed a predictive effect on onset/relapse/recurrence of MDD, but not on time until MDD onset/relapse/recurrence. However, this effect disappeared when studies including participants with a baseline clinical diagnosis were removed from the analyses. Other studies were too heterogeneous to compare. Thus, there is a lack of evidence for leading biological theories for onset and maintenance of depression. Only cortisol was identified as potential predictor for MDD, but results are influenced by the disease state. High-quality (prospective) studies on MDD are needed to disentangle the etiology and maintenance of MDD.
Topics: Biomarkers; Depressive Disorder, Major; Humans; Hydrocortisone; Prospective Studies
PubMed: 31745238
DOI: 10.1038/s41380-019-0585-z -
Depression and Anxiety Feb 2020Varying conceptualizations of treatment-resistant depression (TRD) have made translating research findings or systematic reviews into clinical practice guidelines...
BACKGROUND
Varying conceptualizations of treatment-resistant depression (TRD) have made translating research findings or systematic reviews into clinical practice guidelines challenging and inconsistent.
METHODS
We conducted a review for the Centers for Medicare & Medicaid Services and the Agency for Healthcare Research and Quality to clarify how experts and investigators have defined TRD and to review systematically how well this definition comports with TRD definitions in clinical trials through July 5, 2019.
RESULTS
We found that no consensus definition existed for TRD. The most common TRD definition for major depressive disorder required a minimum of two prior treatment failures and confirmation of prior adequate dose and duration. The most common TRD definition for bipolar disorder required one prior treatment failure. No clear consensus emerged on defining adequacy of either dose or duration. Our systematic review found that only 17% of intervention studies enrolled samples meeting the most frequently specified criteria for TRD. Depressive outcomes and clinical global impressions were commonly measured; functional impairment and quality-of-life tools were rarely used.
CONCLUSIONS
Two key steps are critical to advancing TRD research: (a) Developing a consensus definition of TRD that addresses how best to specify the number of prior treatment failures and the adequacy of dose and duration; and (b) identifying a core package of outcome measures that can be applied in a standardized manner. Our recommendations about stronger approaches to designing and conducting TRD research will foster better evidence to translate into clearer guidelines for treating patients with this serious condition.
Topics: Antidepressive Agents; Bipolar Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Humans; Quality of Life; United States
PubMed: 31638723
DOI: 10.1002/da.22968