Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis

The Lancet, Journal Year: 2018, Volume and Issue: 391(10128), P. 1357 - 1366

Published: Feb. 21, 2018

Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological non-pharmacological treatments are available; however, because inadequate resources, antidepressants used more frequently than psychological interventions. Prescription these agents should be informed by best available evidence. Therefore, we aimed to update expand our previous work compare rank for acute treatment adults with unipolar major disorder.We did a systematic review network meta-analysis. We searched Cochrane Central Register Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, websites regulatory agencies, international registers published unpublished, double-blind, randomised controlled trials from their inception Jan 8, 2016. included placebo-controlled head-to-head 21 (≥18 years old both sexes) diagnosed according standard operationalised criteria. excluded quasi-randomised that were incomplete or 20% participants bipolar disorder, psychotic depression, treatment-resistant depression; patients serious concomitant medical illness. extracted data following predefined hierarchy. In meta-analysis, group-level data. assessed studies' risk bias accordance Handbook Systematic Reviews Interventions, certainty evidence using Grading Recommendations Assessment, Development Evaluation framework. Primary outcomes efficacy (response rate) acceptability (treatment discontinuations due any cause). estimated summary odds ratios (ORs) pairwise meta-analysis random effects. This study registered PROSPERO, number CRD42012002291.We identified 28 552 citations 522 comprising 116 477 participants. terms efficacy, all effective placebo, ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) amitriptyline 1·37 (1·16-1·63) reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) fluoxetine (0·88, 0·80-0·96) associated fewer dropouts whereas clomipramine was worse placebo (1·30, 1·01-1·68). When considered, differences ranged 1·15 1·55 0·64 0·83 wide CrIs on comparative analyses. studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, vortioxetine other (range 1·19-1·96), fluoxetine, fluvoxamine, reboxetine, trazodone least efficacious drugs (0·51-0·84). citalopram, sertraline, tolerable 0·43-0·77), clomipramine, duloxetine, trazodone, venlafaxine had highest dropout rates (1·30-2·32). 46 (9%) rated as high bias, 380 (73%) moderate, 96 (18%) low; moderate very low.All disorder. Smaller active found when analysis, there variability trials. These results serve evidence-based practice inform patients, physicians, guideline developers, policy makers relative merits different antidepressants.National Institute Health Research Oxford Biomedical Centre Japan Society Promotion Science.

Language: Английский

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Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression

Frontiers in Pharmacology, Journal Year: 2018, Volume and Issue: 8

Published: Jan. 17, 2018

Introduction: It is a basic principle of the "psychedelic" treatment model that quality acute experience mediates long-term improvements in mental health. In present paper we sought to test this using data from clinical trial assessing psilocybin for treatment-resistant depression (TRD). line with previous reports, hypothesized occurrence and magnitude Oceanic Boundlessness (OBN) (sharing features mystical-type experience) Dread Ego Dissolution (DED) (similar anxiety) would predict positive outcomes, whereas sensory perceptual effects have negligible predictive value. Materials Methods: Twenty patients resistant underwent (two separate sessions: 10 25 mg psilocybin). The Altered States Consciousness (ASC) questionnaire was used assess experiences session. From ASC, dimensions OBN DED were measure challenging experiences, respectively. Self-Reported Quick Inventory Depressive Symptoms (QIDS-SR) at 5 weeks served as endpoint outcome measure, later time points some subjects had gone on receive new treatments, thus confounding inferences. repeated ANOVA, Time within-subject factor (independent variable), QIDS-SR dependent variable baseline, 1-day, 1-week, 5-weeks. independent variables. OBN-by-Time DED-by-Time interactions primary outcomes interest. Results: For interaction (QIDS-SR main effect each point compared baseline all significant (p = 0.002 p 0.003, respectively, effects), confirming our hypothesis. Furthermore, Pearson's correlation (5 weeks) specific ASC < 0.05). Discussion: This report further bolsters view psychedelic key mediator changes Future therapeutic work psychedelics should recognize essential importance determining efficacy consider ways enhancing reducing anxiety. Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797.

Language: Английский

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The serotonin theory of depression: a systematic umbrella review of the evidence

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(8), P. 3243 - 3256

Published: July 20, 2022

Abstract The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether associated with lowered concentration or activity in a systematic umbrella review the principal relevant areas research. PubMed, EMBASE PsycINFO were searched using terms appropriate each area research, from their inception until December 2020. Systematic reviews, meta-analyses large data-set analyses following identified: metabolite, 5-HIAA, concentrations body fluids; 5-HT 1A receptor binding; transporter (SERT) levels measured by imaging at post-mortem; tryptophan depletion studies; SERT gene associations gene-environment interactions. Studies physical conditions specific subtypes (e.g. bipolar depression) excluded. Two independent reviewers extracted data assessed quality included studies AMSTAR-2, an adapted STREGA for genetic study. certainty study results was modified version GRADE. did not individual because they overlapping studies. registered PROSPERO (CRD42020207203). 17 included: 12 reviews meta-analyses, 1 collaborative meta-analysis, meta-analysis cohort studies, narrative synthesis, association review. Quality variable some high quality. examining showed no (largest n = 1002). One plasma relationship depression, that antidepressant use ( 1869). 561), three binding 1845) weak inconsistent reduced areas, which would be consistent increased synaptic availability people if this original, causal abnormaly. However, effects prior reliably found effect most healthy volunteers 566), but those family history 75). Another 342) sample ten subsequent 407) volunteers. No has been performed since 2007. two largest highest gene, one 115,257) 43,165), revealed interaction between genotype, stress depression. main research provide there being support caused concentrations. Some possibility long-term reduces concentration.

Language: Английский

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The Lancet Psychiatry Commission on psychological treatments research in tomorrow's science

The Lancet Psychiatry, Journal Year: 2018, Volume and Issue: 5(3), P. 237 - 286

Published: Feb. 23, 2018

Language: Английский

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Interventions to support the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic: a mixed methods systematic review

Cochrane library, Journal Year: 2020, Volume and Issue: 2020(11)

Published: Nov. 5, 2020

Language: Английский

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Antidepressant drugs act by directly binding to TRKB neurotrophin receptors

Cell, Journal Year: 2021, Volume and Issue: 184(5), P. 1299 - 1313.e19

Published: Feb. 18, 2021

It is unclear how binding of antidepressant drugs to their targets gives rise the clinical effect. We discovered that transmembrane domain tyrosine kinase receptor 2 (TRKB), brain-derived neurotrophic factor (BDNF) promotes neuronal plasticity and responses, has a cholesterol-sensing function mediates synaptic effects cholesterol. then found both typical fast-acting antidepressants directly bind TRKB, thereby facilitating localization TRKB its activation by BDNF. Extensive computational approaches including atomistic molecular dynamics simulations revealed site at region dimers. Mutation antidepressant-binding motif impaired cellular, behavioral, plasticity-promoting responses in vitro vivo. suggest allosteric facilitation BDNF signaling common mechanism for action, which may explain why act slowly are translated into mood recovery.

Language: Английский

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The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders

Australian & New Zealand Journal of Psychiatry, Journal Year: 2020, Volume and Issue: 55(1), P. 7 - 117

Published: Dec. 22, 2020

Objectives: To provide advice and guidance regarding the management of mood disorders, derived from scientific evidence supplemented by expert clinical consensus to formulate s that maximise utility. Methods: Articles information sourced search engines including PubMed, EMBASE, MEDLINE, PsycINFO Google Scholar were literature known disorders committee (e.g. books, book chapters government reports) published depression bipolar disorder guidelines. Relevant was appraised discussed in detail members committee, with a view formulating developing consensus-based recommendations guidance. The guidelines subjected rigorous consultation external review involving: advisors, key stakeholders, professional bodies specialist groups interest disorders. Results: Royal Australian New Zealand College Psychiatrists practice 2020 (MDcpg ) up-to-date is informed experience. guideline intended for use psychiatrists, psychologists, primary care physicians others an mental health care. Conclusion: MDcpg builds on previous 2015 maintains its joint focus both depressive It provides within evidence-based framework, consensus. Mood committee: Gin S Malhi (Chair), Erica Bell, Darryl Bassett, Philip Boyce, Richard Bryant, Hazell, Malcolm Hopwood, Bill Lyndon, Roger Mulder, Porter, Ajeet B Singh Greg Murray.

Language: Английский

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Cortical GABAergic Dysfunction in Stress and Depression: New Insights for Therapeutic Interventions

Frontiers in Cellular Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: March 12, 2019

Major depressive disorder (MDD) is a debilitating illness characterized by neuroanatomical and functional alterations in limbic structures, notably the prefrontal cortex (PFC), that can be precipitated exposure to chronic stress. For decades, monoaminergic deficit hypothesis of depression provided conceptual framework understand pathophysiology MDD. However, accumulating evidence suggests MDD stress are associated with an imbalance excitation-inhibition (E:I) within PFC, generated inhibitory synaptic transmission onto principal glutamatergic neurons. patients chronically stressed animals show reduction GABA GAD67 levels brain, decreased expression GABAergic interneuron markers, GABAA GABAB receptor levels. Moreover, genetically modified deletion specific receptors subunits or function depressive-like behaviors. Here, we provide further supporting role cortical interneurons, mainly somatostatin- parvalbumin-expressing cells, required for optimal E:I balance PFC discuss how malfunction these cells result depression-related Finally, considering relatively low efficacy current available medications, review new fast-acting pharmacological approaches target system treat We conclude deficits neurotransmission resulting from compromise integrity neurocircuits development other stress-related disorders. Drugs establish targeting systems promising as antidepressants represent breakthrough strategies treatment depression.

Language: Английский

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Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults With Major Depressive Disorder: A Systematic Review and Network Meta-Analysis

FOCUS The Journal of Lifelong Learning in Psychiatry, Journal Year: 2018, Volume and Issue: 16(4), P. 420 - 429

Published: Oct. 1, 2018

(Reprinted with permission from Lancet 2018; 391:1357-66).

Language: Английский

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Role of BDNF in the pathophysiology and treatment of depression: Activity‐dependent effects distinguish rapid‐acting antidepressants

European Journal of Neuroscience, Journal Year: 2019, Volume and Issue: 53(1), P. 126 - 139

Published: Dec. 7, 2019

Abstract The pathophysiology and treatment of depression have been the focus intense research while there is much that remains unknown, modern neurobiological approaches are making progress. This work demonstrates stress associated with atrophy neurons reduced synaptic connectivity in brain regions such as hippocampus prefrontal cortex contribute to depressive behaviors, conversely antidepressant can reverse these deficits. role neurotrophic factors, particularly brain‐derived factor (BDNF), has particular interest factors play a key activity‐dependent regulation plasticity. Here, we review literature demonstrating exposure decreases BDNF expression PFC up‐regulate adult effects stress. We then on rapid‐acting antidepressants, NMDA receptor antagonist ketamine, which produces rapid behavioral actions dependent release BDNF. differs from typical monoaminergic agents require chronic administration produce slow induction expression, consistent time lag for therapeutic action agents. evidence other classes also release, this common, convergent downstream mechanism. Finally, discuss ketamine another growth factor, vascular endothelial (VEGF) its complex interplay

Language: Английский

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