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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 -
Journal of Affective Disorders Jan 2021Ketamine appears to have a therapeutic role in certain mental disorders, most notably depression. However, the comparative performance of different formulations of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ketamine appears to have a therapeutic role in certain mental disorders, most notably depression. However, the comparative performance of different formulations of ketamine is less clear.
OBJECTIVES
This study aimed to assess the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar major depression.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
We searched PubMed, MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for relevant studies published since database inception and December 17, 2019.
STUDY ELIGIBILITY CRITERIA
We considered randomized controlled trials examining racemic or esketamine for the treatment of unipolar or bipolar major depression.
OUTCOMES
Primary outcomes were response and remission from depression, change in depression severity, suicidality, retention in treatment, drop-outs, and drop-outs due to adverse events.
ANALYSIS
Evidence from randomized controlled trials was synthesized as rate ratios (RRs) for treatment response, disorder remission, adverse events, and withdrawals and as standardized mean differences (SMDs) for change in symptoms, via random-effects meta-analyses.
FINDINGS
24 trials representing 1877 participants were pooled. Racemic ketamine relative to esketamine demonstrated greater overall response (RR = 3.01 vs. RR = 1.38) and remission rates (RR = 3.70 vs. RR = 1.47), as well as lower dropouts (RR = 0.76 vs. RR = 1.37).
CONCLUSIONS
Intravenous ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Major; Humans; Ketamine
PubMed: 33022440
DOI: 10.1016/j.jad.2020.09.071 -
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 -
The Lancet. Psychiatry Nov 2022Ketamine has rapid yet often transient antidepressant effects in patients with treatment-resistant depression. Different strategies have been proposed to prolong these... (Review)
Review
Ketamine has rapid yet often transient antidepressant effects in patients with treatment-resistant depression. Different strategies have been proposed to prolong these effects. Maintenance ketamine treatment appears promising, but little is known about its efficacy, safety, and tolerability in depression. We searched Pubmed, Embase, and the Cochrane Library and identified three randomised controlled trials, eight open-label trials, and 30 case series and reports on maintenance ketamine treatment. We found intravenous, intranasal, oral, and possibly intramuscular and subcutaneous maintenance ketamine treatment to be effective in sustaining antidepressant effect in treatment-resistant depression. Tachyphylaxis, cognitive impairment, addiction, and serious renal and urinary problems seem uncommon. Despite the methodological limitations, we conclude that from a clinical view, maintenance ketamine treatment seems to be of therapeutic potential. We recommend both controlled and naturalistic studies with long-term follow-up and sufficient power to determine the position of maintenance ketamine treatment within routine clinical practice.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Treatment-Resistant; Humans; Ketamine
PubMed: 36244360
DOI: 10.1016/S2215-0366(22)00317-0 -
Psychiatry Research Nov 2023The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive... (Meta-Analysis)
Meta-Analysis Review
The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. Systematic searches were conducted to search for randomized clinical trials and open-label trials that evaluated depression symptoms after psilocybin therapy. Data was pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in depression severity, determined by calculating the change in depression ratings from baseline to the primary endpoint in the psilocybin arm versus the control arm. The literature search yielded 1734 studies, and 13 studies (n = 686) were included in either qualitative and/or quantitative analyses. The meta-analysis included 9 studies (pooled n = 596) and yielded a large effect size in favour of psilocybin (SMD = -0.78; p<0.001). Risk ratios for response and remission were large and significant in favour of psilocybin. A review of open-label trials showed robust decreases in depressive symptoms following psilocybin administration. These findings provide preliminary evidence for antidepressant efficacy with psilocybin-assisted psychotherapy, however, further studies are needed to evaluate safety and efficacy and to optimize treatment protocols.
Topics: Humans; Psilocybin; Depression; Depressive Disorder, Major; Psychotherapy; Antidepressive Agents; Hallucinogens
PubMed: 37844352
DOI: 10.1016/j.psychres.2023.115531 -
Nutritional Neuroscience Jul 2023Individuals with bipolar disorder (BD) have higher rates of unhealthy lifestyles and risk for medical comorbidities Research currently suggests that dietary factors may...
INTRODUCTION
Individuals with bipolar disorder (BD) have higher rates of unhealthy lifestyles and risk for medical comorbidities Research currently suggests that dietary factors may play a role in the development of depression and anxiety. Therefore, nutritional approaches are potential strategies for the treatment of BD. The aim of this review is to summarize the available evidence on nutrition and BD.
MATERIALS AND METHODS
The paper was developed based on PRISMA 2020 guidelines. The search was conducted in Sep-2021 using PubMed and Cochrane Library, augmented by manually checked references lists. The search found 986 studies, of which 47 were included, combined with 13 from reference lists, totaling 60 studies.
RESULTS
There were 33 observational trials, of which 15 focused on fatty acids, 9 on micronutrients, 5 on specific foods, 4 on macro and micronutrients. The 27 interventional studies mainly focused on fatty acids, micronutrients and N-acetylcysteine (NAC).
DISCUSSION
Dietary intake or supplementation of unsaturated fatty acids, mainly Omega-3 seems to be associated with improved BD symptoms, along with seafood, folic acid and zinc. Studies found variable, mainly non-significant impacts of creatine, carnitine, vitamin D, inositol or NAC supplementation on BD. There are promising results associated with Coenzyme Q10 (Coq10) and probiotics. Taken together, these preliminary findings suggest that dietetic approaches might be included as part of BD treatment. Also considering the high risk of metabolic disorders in individuals with BD, they should be encouraged to choose healthy dietary lifestyles, including daily intake of fruits, vegetables, seafood and whole grains.
Topics: Humans; Bipolar Disorder; Diet; Vitamins; Micronutrients; Fatty Acids, Omega-3; Acetylcysteine
PubMed: 35608150
DOI: 10.1080/1028415X.2022.2077031 -
Molecular Psychiatry Apr 2022The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry.... (Review)
Review
The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.
Topics: Bipolar Disorder; Brain; Depressive Disorder, Major; Gastrointestinal Microbiome; Humans; Schizophrenia
PubMed: 35194166
DOI: 10.1038/s41380-022-01456-3 -
Canadian Journal of Psychiatry. Revue... Jan 2023Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for... (Review)
Review
OBJECTIVE
Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder.
METHODS
A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria.
RESULTS
Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient.
CONCLUSIONS
There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.
Topics: Humans; Hallucinogens; Psilocybin; Depressive Disorder, Major; Canada; Anxiety; Neoplasms
PubMed: 35975555
DOI: 10.1177/07067437221111371 -
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 -
JAMA Network Open Jun 2022New and expectant parents experience perinatal mood disorders, with consequences to parenting ability, bonding with the neonate, interpersonal relationships, and health... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
New and expectant parents experience perinatal mood disorders, with consequences to parenting ability, bonding with the neonate, interpersonal relationships, and health and well-being of parents. Research shows that maternal and paternal perinatal mood disorders are associated, but no recent systematic review has addressed the prevalence of perinatal mood disorders in both mothers and fathers (parental dyad).
OBJECTIVE
To examine the prevalence of perinatal mood disorders in parental dyads and identify factors associated with perinatal mood disorders in parental dyads.
DATA SOURCES
Ovid (MEDLINE, Embase, and PsycINFO) and Web of Science were searched from January 1, 1990, to June 8, 2021, for observational studies reporting on the prevalence of perinatal depression or anxiety in a parental dyad.
STUDY SELECTION
Studies reporting the prevalence of anxiety or depression in both members of a parental dyad were included, with diagnosis according to established criteria (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition], International Classification of Diseases, 11th Revision) or use of validated screening tools.
DATA EXTRACTION AND SYNTHESIS
Prevalence data were extracted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were analyzed in subgroups: antenatal depression, early postnatal depression (0-12 weeks), late postnatal depression (3-12 months), and perinatal anxiety. Pooled prevalence was calculated using a random-effects meta-analysis model. Quality assessment was performed using Joanna Briggs Institute Appraisal Checklist for Studies Reporting Prevalence Data. Data were analyzed in June 2021.
MAIN OUTCOMES AND MEASURES
Prevalence of perinatal anxiety and perinatal depression in parental dyads.
RESULTS
Twenty-three studies were included, with data from 29 286 couples. The pooled prevalence of antenatal depression in both parents was 1.72% (95% CI, 0.96%-2.48%; P < .001). The prevalence of early postnatal depression (up to 12 weeks post partum) was 2.37% (95% CI, 1.66%-3.08%; P < .001) and the prevalence of late postnatal depression (3-12 months post partum) was 3.18% (95% CI, 2.3-4.05; P < .001). Only 3 studies reported on perinatal anxiety in both parents, precluding a quantitative analysis.
CONCLUSIONS AND RELEVANCE
In up to 3.18% of couples, both parents may concurrently experience perinatal depression. Perinatal health care must consider the mental health needs of parents, both as individuals and as a parental dyad. Further research is needed to examine outcomes in families where both parents experience perinatal mood disorders.
Topics: Anxiety; Depression; Depression, Postpartum; Female; Humans; Infant, Newborn; Parents; Pregnancy; Prevalence
PubMed: 35749112
DOI: 10.1001/jamanetworkopen.2022.18969