Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(3), P. 394 - 412

Published: Sept. 15, 2023

Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD demonstrated predictive utility in terms clinical decision-making outcomes does not currently exist. Instead, a plethora definitions have been proposed, which vary significantly their conceptual framework. The absence hampers precise estimates the prevalence TRD, also belies efforts to identify risk factors, prevention opportunities, effective interventions. In addition, it results heterogeneity practice decision-making, adversely affecting quality care. US Food Drug Administration (FDA) European Medicines Agency (EMA) adopted most used (i.e., inadequate response minimum two antidepressants despite adequacy treatment trial adherence treatment). It estimated that at least 30% persons meet this definition. significant percentage are actually pseudo-resistant (e.g., due inadequacy trials or non-adherence Although sociodemographic, clinical, contextual factors known negatively moderate depression, very few regarded as non-response across modalities treatment. Intravenous ketamine intranasal esketamine (co-administered an antidepressant) established efficacious management TRD. Some second-generation antipsychotics aripiprazole, brexpiprazole, cariprazine, quetiapine XR) proven adjunctive treatments partial responders, but only olanzapine-fluoxetine combination has studied FDA-defined Repetitive transcranial magnetic stimulation (TMS) FDA-approved for individuals accelerated theta-burst TMS recently showing efficacy. Electroconvulsive therapy acute maintenance intervention preliminary evidence suggesting non-inferiority intravenous ketamine. Evidence extending antidepressant trial, medication switching combining mixed. Manual-based psychotherapies on own offer symptomatic relief when added conventional antidepressants. Digital therapeutics under study represent potential future vista population.

Language: Английский

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Reporting guidelines for Delphi techniques in health sciences: A methodological review

Zeitschrift für Evidenz Fortbildung und Qualität im Gesundheitswesen, Journal Year: 2022, Volume and Issue: 172, P. 1 - 11

Published: June 17, 2022

Delphi techniques are conducted across different subfields in the health sciences. The reporting practices of studies using vary, and current guidelines for focus on individual sciences or aspects research therefore limited applicability. aim this article was to identify similarities, differences, possible shortcomings existing draft an initial proposal a comprehensively applicable guideline.A systematic literature search performed data resources based databases (Scopus, MEDLINE, CINAHL, Epistemonikos) including publications from 2016 2021. In June 2021, we additional PubMed included further by contacting experts scientific expert network (DeWiss). Title abstract screening articles performed, followed full-text included. We qualitatively quantitatively evaluated, compared contrasted identified content analysis discussed results among members network.We retrieved ten science with studies. analyzing them, nine main categories (Justification, Expert panel, Questionnaire, Survey design, Process regulation, Analyses, Results, Discussion, Methods reflection & Ethics). vary significantly, only aspect consensus appearing all them. Frequency distributions show that most subcategories addressed (e.g., meeting participants, proceeding survey method, transfer results, validation, prevention bias) epistemological foundations technique rarely mentioned reflected on. drafted sector.A well-justified position concerning is necessary make quality process assessable and, along process, classify compare study results. This will increase acceptance both method sector medical practice. A guideline must, above all, take into account diversity variants, subfield-related objectives application areas, their modifications order be sciences.The our methodological review do not provide final guideline. newly developed intended encourage discussion agreement analyses.

Language: Английский

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Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication

Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 48(10), P. 1492 - 1499

Published: July 13, 2023

Psilocybin is being investigated as a treatment in adults with treatment-resistant depression (TRD). Withdrawal from serotonergic antidepressant drugs common prerequisite for taking part trials of psilocybin due to the possibility ongoing altering psychedelic effect. This phase II, exploratory, international, fixed-dose, open-label study explored safety, tolerability, and efficacy synthetic form (investigational drug COMP360) adjunct selective serotonin reuptake inhibitor participants TRD. Participants received single 25 mg dose alongside psychological support were followed-up 3 weeks. The primary end point was change Montgomery-Åsberg Depression Rating Scale (MADRS) total score Baseline at Week 3. Secondary points including treatment-emergent adverse events (TEAEs), proportion responders remitters 3, Clinical Global Impression-Severity (CGI-S) score. Nineteen dosed mean MADRS 31.7 (SD = 5.77). Twelve (63.2%) had TEAE, most which mild resolved on day onset. There no serious TEAEs or indication increased suicidal ideation behavior. At -14.9 (95% CI, -20.7 -9.2), -1.3 1.29) CGI-S. Both response remission evident 8 (42.1%) participants. Larger, comparator-controlled are necessary understand if this paradigm can optimize treatment-outcome where withdrawal would be problematic.

Language: Английский

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Low-dose interleukin 2 antidepressant potentiation in unipolar and bipolar depression: Safety, efficacy, and immunological biomarkers

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 118, P. 52 - 68

Published: Feb. 15, 2024

Immune-inflammatory mechanisms are promising targets for antidepressant pharmacology. Immune cell abnormalities have been reported in mood disorders showing a partial T defect. Following this line of reasoning we defined an potentiation treatment with add-on low-dose interleukin 2 (IL-2). IL-2 is T-cell growth factor which has proven anti-inflammatory efficacy autoimmune conditions, increasing thymic production naïve CD4 + cells, and possibly correcting the defect observed disorders. We performed single-center, randomised, double-blind, placebo-controlled phase II trial evaluating safety, clinical biological responses depressed patients major depressive (MDD) or bipolar disorder (BD). 36 consecutively recruited inpatients at Mood Disorder Unit were randomised 2:1 ratio to receive either aldesleukin (12 MDD 12 BD) placebo (6 6 BD). Active significantly potentiated response ongoing SSRI/SNRI both diagnostic groups, expanded population regulatory, helper 2, percentage Naive CD4+/CD8 immune cells. Changes frequences rapidly induced first five days treatment, predicted later improvement depression severity. No serious adverse effect was observed. This control (RCT) evidence supporting hypothesis that strengthen system could be successful way correct immuno-inflammatory associated disorders, potentiate response.

Language: Английский

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Emerging Medications for Treatment-Resistant Depression: A Review with Perspective on Mechanisms and Challenges

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(2), P. 161 - 161

Published: Feb. 6, 2025

Background/Objectives: Non-response to initial treatment options for major depressive disorder (MDD) is a common clinical challenge with profound deleterious impacts affected patients. Few treatments have received regulatory approval treatment-resistant depression (TRD). Methods: A systematic search of United States and European Union trials registries was conducted identify Phase II, III, or IV trials, last update posted on after 1 January 2020, that were evaluating medications TRD. For both the US EU registries, condition term "treatment resistant depression" associated lower-level terms (per registry protocol) used. registry, secondary using "depressive disorders" modifying "inadequate" also performed capture registrations not tagged as Two additional searches in "suicide" "anhedonia" transdiagnostic targets investigational medications. Trials categorized based primary mechanism action trial's medication. Results: Fifty TRD, 20 anhedonia, 25 suicide identified. Glutamate system modulation currently most compounds development, including antagonists allosteric modulators NMDA receptors, AMPA metabotropic type 2/3 glutamate intracellular effector molecules downstream signaling. Psychedelics seen greatest surge among mechanistic past 5 years, however, psilocybin particular garnering significant attention. Other mechanisms included GABA modulators, monoamine anti-inflammatory/immune-modulating agents, an orexin 2 receptor antagonist. Conclusions: These investigations offer substantial promise more efficacious potentially personalized medication approaches Challenges detecting efficacy TRD include heterogeneity within population stemming from presumed variety biological dysfunctions underlying disorder, comorbid disorders, chronic psychosocial stressors, enduring effects prior serotonergic antidepressant treatments.

Language: Английский

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The opioid system in depression

Neuroscience & Biobehavioral Reviews, Journal Year: 2022, Volume and Issue: 140, P. 104800 - 104800

Published: July 30, 2022

Language: Английский

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Brain-Derived Neurotrophic Factor (BDNF) as a biomarker of treatment response in patients with Treatment Resistant Depression (TRD): A systematic review & meta-analysis

Psychiatry Research, Journal Year: 2022, Volume and Issue: 317, P. 114857 - 114857

Published: Sept. 21, 2022

Language: Английский

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On model-based time trend adjustments in platform trials with non-concurrent controls

BMC Medical Research Methodology, Journal Year: 2022, Volume and Issue: 22(1)

Published: Aug. 15, 2022

Abstract Background Platform trials can evaluate the efficacy of several experimental treatments compared to a control. The number is not fixed, as arms may be added or removed trial progresses. are more efficient than independent parallel group because using shared control groups. However, for treatment entering at later time point, divided into concurrent controls, consisting patients randomised when that arm in platform, and non-concurrent before. Using controls addition improve trial’s efficiency by increasing power reducing required sample size, but introduce bias due trends. Methods We focus on platform with two common arm. Assuming second time, we assess robustness recently proposed model-based approaches adjust trends utilizing controls. In particular, consider where modeled either linear step function, steps points enter leave trial. For continuous binary outcomes, investigate type 1 error rate testing newly arm, well root mean squared effect estimates under range scenarios. scenarios equal across arms, settings different additive scale model. Results A function model, fitted data from all gives increased while controlling error, long model scale. This holds even if shape trend deviates allocated block randomisation. differ between effects inflated. Conclusions gained models incorporate outweigh potential risks biases, especially small sizes. Such biases arise assumptions equality additivity satisfied. specifics trial, scientific plausibility trends, results should carefully considered.

Language: Английский

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Rethinking ketamine and esketamine action: Are they antidepressants with mood-stabilizing properties?

European Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 70, P. 49 - 55

Published: March 1, 2023

Language: Английский

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Sickness behaviour and depression: An updated model of peripheral-central immunity interactions

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 111, P. 202 - 210

Published: April 17, 2023

Current research into mood disorders indicates that circulating immune mediators participating in the pathophysiology of chronic somatic have potent influences on brain function. This paradigm has brought to fore use anti-inflammatory therapies as adjunctive standard antidepressant therapy improve treatment efficacy, particularly subjects do not respond medication. Such new practice requires biomarkers tailor these those most likely benefit but also validated mechanisms action describing interaction between peripheral immunity and function optimize target intervention. These are generally studied preclinical models try recapitulate human disease, MDD, through peripherally induced sickness behaviour. In this proposal paper, after an appraisal data rodent their adherence clinical cohorts, we put forward a modified model periphery-brain interactions goes beyond currently established view microglia cells drivers depression. Instead, suggest that, for patients with mild levels inflammation, barriers primary actors disease resistance. We then highlight gaps novel lines research.

Language: Английский

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