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treatment-resistant depression
Also known as: TRD, treatment-resistant unipolar depression
Facts (80)
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The Montreal model: an integrative biomedical-psychedelic ... frontiersin.org 60 facts
claimRegulatory approvals for treatment-resistant depression (TRD) are limited to a small number of specific treatments, including transcranial magnetic stimulation (such as the Stanford Accelerated Intelligent Neuromodulation Therapy), the combination of olanzapine and fluoxetine, and intranasal esketamine.
claimKetamine is considered a putative psychedelic with several advantages, including a long medical track record, efficacy in treating severe Treatment-Resistant Depression (TRD) and suicidality, treatment sessions that are approximately 75% shorter than other psychedelic therapies, minimal drug–drug interactions, and safety in patients with bipolar affective disorder 1.
claimThe Montreal model of ketamine treatment for Treatment-Resistant Depression (TRD) occupies a middle-ground between biomedical and psychedelic approaches to ketamine administration.
referenceJohnston et al. conducted a systematic review of the economic and quality of life literature regarding the burden of treatment-resistant depression, published in the Journal of Affective Disorders in 2019.
accountThe Montreal model was developed over 6 years and based on more than 500 ketamine treatments administered to inpatients and outpatients with severe treatment-resistant depression at two McGill University hospitals.
referenceS.T. Wilkinson, T.G. Rhee, J. Joormann, R. Webler, M. Ortiz Lopez, B. Kitay, et al. published 'Cognitive behavioral therapy to sustain the antidepressant effects of ketamine in treatment-resistant depression: a randomized clinical trial' in PPS in 2021.
claimThe Montreal model was developed to create a structured approach to ketamine treatment that is applicable to complex, real-world Treatment-Resistant Depression (TRD) patients and feasible for implementation in resource-limited public healthcare systems.
claimThe Montreal model is an approach to integrating ketamine into a broader biopsychosocial intervention for treatment-resistant depression, designed to deliver feasible and robust clinical benefits.
measurementThe Montreal team's IV ketamine service for Treatment-Resistant Depression (TRD) resulted in rapid improvements in depression and suicidality in approximately 50% of patients, with these effects generally fading within days or weeks of the last dose.
referenceZhou et al. conducted a systematic review and network meta-analysis on the comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression, published in the Journal of Clinical Psychiatry in 2015.
referenceMathew et al. (2019) published the ELEKT-D study protocol in Contemporary Clinical Trials, which compares electroconvulsive therapy (ECT) to ketamine for patients with treatment-resistant depression.
referenceA 2018 Cochrane review of psychotherapy for treatment-resistant depression, which analyzed six trials involving 698 participants, concluded that while various approaches like Cognitive Behavioral Therapy (CBT) have high acceptability, they provide only modest improvements.
referenceDemyttenaere and Van Duppen (2019) published 'The impact of (the concept of) treatment-resistant depression: an opinion review' in the International Journal of Neuropsychopharmacology.
referenceBrendle et al. (2022) analyzed the cost-effectiveness of esketamine nasal spray compared to intravenous ketamine for patients with treatment-resistant depression in the United States, utilizing clinical trial efficacy and real-world effectiveness estimates.
claimThe authors of the Montreal model suggest that establishing a 'psychotherapy-grade' therapeutic frame is vital for the safety and efficacy of ketamine treatment, especially when treating treatment-resistant depression (TRD) in patients with comorbidities like personality disorders.
referenceIjaz et al. published a 2018 Cochrane Database of Systematic Reviews study on psychological therapies for adults with treatment-resistant depression.
referenceLi et al. conducted a cohort study on all-cause mortality in patients with treatment-resistant depression within the US population, published in Annals of General Psychiatry in 2019.
claimIn the Montreal model, as patients with treatment-resistant depression improve, treatment goals evolve from evidence-based lifestyle changes to 'committed action' goals that align with an individual's unique values, consistent with Acceptance and Commitment Therapy (ACT).
referenceHeerlein et al. conducted a 2021 European cohort study published in the Journal of Affective Disorders examining treatment patterns and clinical outcomes for patients with treatment-resistant depression.
claimBiological models for treatment-resistant depression (TRD) that fail to address sociopsychological factors can paradoxically reinforce symptoms such as demoralization, passivity, and guilt.
claimThe Montreal model clinicians suggest that the psychological processes underlying psychedelic ketamine experiences are not specific to ketamine or Treatment-Resistant Depression, but may arise in any therapeutic situation where a patient receives a powerful psychoactive drug with psychological accompaniment.
claimThe Montreal model for treating patients with treatment-resistant depression (TRD) often involves setting goals such as 20 minutes of daily walking and establishing fixed sleeping hours to address irregular routines and behavioral deactivation.
measurementIn a cohort study of treatment-resistant depression (TRD) patients receiving ketamine under the Montreal model, all patients were willing to attempt benzodiazepine receptor (BZDR) discontinuation, nearly all achieved total abstinence during treatment, and the majority remained BZDR-free after an average follow-up of one year.
referenceBozymski et al. published a review on esketamine as a novel option for treatment-resistant depression in the Annals of Pharmacotherapy in 2020.
claimSubanesthetic intravenous (IV) racemic ketamine, an N-methyl-D-aspartate (NMDA) antagonist, produces rapid and potent antidepressant effects in patients with treatment-resistant depression.
referenceJaffe et al. (2019) published 'The humanistic and economic burden of treatment-resistant depression in Europe: a cross-sectional study' in BMC Psychiatry.
referenceFekadu et al. conducted a systematic review of medium to long-term outcome studies for patients with treatment-resistant depression, published in the Journal of Affective Disorders in 2009.
perspectiveThe Montreal model clinical team recommends reducing the use of benzodiazepines and related sedatives (BZDRs) for patients with treatment-resistant depression, citing evidence of tolerance, potential harms, and questionable long-term efficacy.
claimTreatment-resistant depression is typically defined as a lack of meaningful improvement to at least two adequate trials of antidepressants.
measurementA 12-month cohort study of 411 patients with treatment-resistant depression across multiple European countries found that only about 30% of patients achieved a clinical response after 6–12 months of continual treatment.
claimElectroconvulsive therapy (ECT) is considered the most evidence-based treatment option for treatment-resistant depression, though it is associated with stigma, inconsistent availability, and side effects such as amnesia due to the requirement for general anesthesia.
measurementMeta-analysis indicates that approximately 50% of patients with treatment-resistant depression experience a greater than 50% improvement in depressive symptoms within hours or days of receiving a single 40-minute intravenous ketamine infusion.
referenceLundberg et al. performed a population-wide study on the association of treatment-resistant depression with patient outcomes and health care resource utilization, published in JAMA Psychiatry in 2022.
accountThe Montreal model of psychedelic therapy was evaluated in a randomized controlled trial (RCT) examining the effects of music on ketamine infusions in patients with treatment-resistant depression (TRD).
claimPatients with treatment-resistant depression (TRD) exhibit high rates of psychiatric comorbidities, including anxiety disorders, sleep disorders, substance abuse, personality disorders, and intentional self-harm.
procedureThe Montreal model maintenance phase for treatment-resistant depression (TRD) consists of three forms: medication/neurostimulation, concomitant psychotherapy, and maintenance ketamine treatments.
referenceMcMullen et al. published a 2021 study in Advances in Therapy regarding strategies to prolong the efficacy of ketamine in adults with treatment-resistant depression.
referenceBahr et al. (2019) discussed the use of intranasal esketamine (Spravato) in conjunction with oral antidepressants for the treatment of treatment-resistant depression in the journal P&T.
claimThe antidepressant benefits of ketamine for treatment-resistant depression typically fade within days or weeks of administration.
referenceReutfors et al. conducted a register-based cohort study on mortality in treatment-resistant unipolar depression in Sweden, published in the Journal of Affective Disorders in 2018.
claimThe Montreal model aims to facilitate experiential learning with ketamine treatments to cultivate engaged, collaborative, and flexible life orientations as a corrective force to the passivity, rigidity, and nihilism commonly found in Treatment-Resistant Depression (TRD).
claimThe Montreal team implemented and evaluated diverse nonpharmacological strategies to improve the sustained efficacy and tolerability of their ketamine intervention for Treatment-Resistant Depression (TRD).
referenceThe National Institute for Health and Care Excellence (NICE) issued clinical guidance in 2022 recommending the use of esketamine nasal spray for treatment-resistant depression.
claimA 2023 preliminary report by Garel et al. in Neuropsychopharmacology examined the use of intravenous ketamine for benzodiazepine deprescription and withdrawal management in patients with treatment-resistant depression.
referenceCole et al. published a study on Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) for treatment-resistant depression in the American Journal of Psychiatry in 2020.
claimA notable strength of the ketamine clinical literature is the frequent inclusion of real-world treatment-resistant depression (TRD) patients who are often excluded from other clinical trials due to severity and comorbidity.
claimBoth intravenous racemic ketamine and intranasal esketamine are currently used in various models of care for treatment-resistant depression (TRD) due to meta-analytic evidence of their antidepressant effects and the high demand for novel treatments.
referenceThe Montreal model is a comprehensive biopsychosocial approach to using ketamine for severe treatment-resistant depression that was refined over six years in public healthcare settings.
claimIn a 12-month cohort study of 411 patients with treatment-resistant depression, 60% of patients experienced no changes to their treatment regimen despite poor clinical outcomes, indicating therapeutic inertia or nihilism.
accountThe Montreal team established an intravenous (IV) ketamine service for Treatment-Resistant Depression (TRD) that utilized an electroconvulsive therapy (ECT)-like model of care and standard dosing protocols.
claimTreatment-resistant depression is associated with greater functional impairment, elevated risks of repeated episodes, and increased long-term mortality, both overall and specifically by suicide.
claimPsychedelic-Assisted Psychotherapy (PAP) has demonstrated significant benefits in treating Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD), though current practices are heterogeneous and ill-defined.
claimClinical practice for treatment-resistant depression often involves the off-label use of various pharmacological agents, including second-generation antipsychotics, lithium, and thyroid hormones.
claimSubanesthetic ketamine has accumulated meta-analytic evidence for rapid antidepressant effects in treatment-resistant depression, which has generated both excitement and debate regarding its mechanisms of action and integration into psychiatric care.
referenceNemeroff (2007) published 'Prevalence and management of treatment-resistant depression' in the Journal of Clinical Psychiatry.
referenceMarkowitz et al. (2022) addressed the neglected role of psychotherapy in the treatment of treatment-resistant depression.
referenceThe Montreal model of ketamine for treatment-refractory depression is a biopsychosocial approach developed gradually over years of real-world clinical experiences and research endeavors.
perspectiveThe Montreal model researchers hypothesize that their 'slower-but-steadier' endeavor is better suited to complex patients suffering from severe and chronic treatment-resistant depression (TRD) because the six treatment visits provide multiple opportunities to engage in the treatment process, revisit behavioral goals, and consolidate insights.
claimThe most common strategy for prolonging the benefits of ketamine in treatment-resistant depression is the readministration of ketamine, despite a lack of evidence regarding the long-term safety, efficacy, and feasibility of this practice.
measurementA recent review identified five small trials studying ketamine-psychotherapy combinations, none of which were psychedelic in their therapeutic approach and only one of which focused on treatment-resistant depression.
Neuroimaging in psychedelic drug development: past, present, and ... nature.com Sep 27, 2023 7 facts
claimThe first open-label study of psilocybin for treatment-resistant depression showed that changes in cerebral blood flow in the amygdala, measured with arterial spin-labelling MRI, correlated with changes in depression scores.
claimPsilocybin therapy for treatment-resistant depression is associated with changes in amygdala and prefrontal functional connectivity during emotional processing, as reported in a 2020 study.
referenceCarhart-Harris et al. (2017) used fMRI to measure brain mechanisms associated with the use of psilocybin for treatment-resistant depression.
claimResearch on the cohort from the first open-label psilocybin study for treatment-resistant depression found increased amygdala responses to emotional stimuli, that changes in amygdala connectivity predict some clinical outcomes, and that patients show increased brain response to music stimuli following treatment.
claimPatients with treatment-resistant depression treated with psilocybin showed differences in the functional connectivity of the medial pre-frontal cortex and hippocampus.
referenceCarhart-Harris et al. (2016) conducted an open-label feasibility study on the use of psilocybin with psychological support for treatment-resistant depression.
referenceRoseman et al. (2018) observed increased amygdala responses to emotional faces in patients after receiving psilocybin for treatment-resistant depression.
Effects of psychedelics on neurogenesis and broader neuroplasticity link.springer.com Dec 19, 2024 5 facts
claimMuscat S-A, Hartelius G, Crouch CR, and Morin KW proposed an integrative approach to ketamine therapy in 2021, suggesting it may enhance multiple dimensions of efficacy for treating treatment-resistant depression.
claimHaile et al. (2014) investigated the relationship between plasma brain-derived neurotrophic factor (BDNF) levels and the response to ketamine in patients with treatment-resistant depression.
measurementApproximately 50 to 60% of patients do not experience positive outcomes from standard antidepressant drug classes, leading to a condition known as treatment-resistant depression (TRD).
measurementIn treatment-resistant depression (TRD) patients, non-responsiveness to ketamine treatment is correlated with decreased brain-derived neurotrophic factor (BDNF) levels 7 and 14 days after a single 0.5 mg/kg ketamine infusion.
claimKetamine is a prescriptible treatment for treatment-resistant depression (TRD) in the USA and Israel, with many other countries implementing this treatment, according to Mathai et al. (2020).
Psychedelics, Sociality, and Human Evolution frontiersin.org 4 facts
referenceR. Watts, C. Day, J. Krzanowski, and R. Carhart-Harris (2017) documented patients' accounts of increased 'connectedness' and 'acceptance' following psilocybin treatment for treatment-resistant depression.
referenceThe edited volume by Winkelman and Sessa (2019) contains reviews of clinical evidence demonstrating the therapeutic effectiveness of psychedelics for treating anxiety, trauma, treatment-resistant depression, and personality, inflammatory, and autoimmune conditions.
measurementPatients with treatment-resistant depression (n=20) showed increased agreeableness and decreased neuroticism sustained at a 6-month follow-up after ayahuasca administration, according to Netzband et al. (2020).
measurementPatients with treatment-resistant depression (n=20) exhibited decreased disconnection, decreased avoidance of difficult emotions, and increased acceptance following psilocybin administration in a 2017 study.
Ancient Roots of Today's Emerging Renaissance in ... link.springer.com 3 facts
referenceRosalind Watts, Camilla Day, Jacob Krzanowski, David J. Nutt, and Robin Carhart-Harris reported in 2017 that patients experienced increased feelings of 'connectedness' and 'acceptance' following psilocybin treatment for treatment-resistant depression.
referenceLeor Roseman, David J. Nutt, and Robin Carhart-Harris published 'Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression' in Frontiers of Pharmacology in 2018.
referenceSalahudeen, Wright, and Peterson (2020) conducted a narrative review evaluating esketamine as a potential treatment for treatment-resistant depression.
Published Studies — Johns Hopkins Center for Psychedelic and ... hopkinspsychedelic.org 1 fact
referenceGukasyan, N. published 'On blinding and suicide risk in a recent trial of psilocybin-assisted therapy for treatment-resistant depression' in Med in 2023.