The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.

Objective: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

Methods: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support.

The impact of antidepressant discontinuation prior to treatment with psilocybin for treatment-resistant depression.

It has been suggested that the recent use and discontinuation of antidepressant drugs compromises the action of psilocybin. As evidence is only available from small or uncontrolled samples, this post hoc analysis investigated this using data from the largest, phase II, randomized controlled trial of psilocybin treatment to date. Data from 233 participants with treatment-resistant depression (TRD) who received 25 mg, 10 mg, or 1 mg of investigational drug COMP360 psilocybin (a proprietary, pharmaceutical-grade synthetic psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.

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

Psilocybin is being investigated as a treatment in adults with treatment-resistant depression (TRD). Withdrawal from serotonergic antidepressant drugs is a common prerequisite for taking part in trials of psilocybin due to the possibility of ongoing antidepressant drugs altering the psychedelic effect. This phase II, exploratory, international, fixed-dose, open-label study explored the safety, tolerability, and efficacy of a synthetic form of psilocybin (investigational drug COMP360) adjunct to a selective serotonin reuptake inhibitor in participants with TRD.

The Fake IQ Test: a novel measure of self-reflection in major depressive disorder.

Background: Excessive negative self-referential processing plays an important role in the development and maintenance of major depressive disorder (MDD). Current measures of self-reflection are limited to self-report questionnaires and invoking imagined states, which may not be suitable for all populations.

Aims: The current study aimed to pilot a new measure of self-reflection, the Fake IQ Test (FIQT).

Unblinding and demand characteristics in the treatment of depression.

Blinding of treatment allocation in clinical trials in psychiatry is regarded as an ideal. The potential impact of unblinding chimes with a general concern for psychological research: so-called demand characteristics can undermine confidence in findings from experimental and clinical studies. Scepticism can result in nihilism.

Observational study to characterize treatment-resistant depression in Germany, France and the United Kingdom: analysis of real-world data collected through a survey of healthcare professionals.

Objective: This study describes treatment patterns, productivity, healthcare resource utilization and previous episodes of depression for patients with treatment-resistant depression (TRD).

Methods: In this cross-sectional study, a quantitative survey was administered to 225 healthcare providers (HCPs) distributed evenly across Germany, France and the UK from July to August 2021. Each HCP was asked to answer based on medical records of five patients with TRD, defined as patients failing to respond to two or more treatments of adequate dose and duration in the same episode of major depressive disorder (MDD), which provided a sample size of 1125 patients.

Brain activity during pursuit and goal-conflict threat avoidance in major depressive disorder.

Threat avoidance is a prominent symptom of affective disorders, yet its biological basis remains poorly understood. Here, we used a validated task, the Joystick Operated Runway Task (JORT), combined with fMRI, to explore whether abnormal function in neural circuits responsible for avoidance underlies these symptoms. Eighteen individuals with major depressive disorder (MDD) and 17 unaffected controls underwent the task, which involved using physical effort to avoid threatening stimuli, paired with mild electric shocks on certain trials.

Systematic review and meta-analysis of augmentation and combination treatments for early-stage treatment-resistant depression.

Background: Major depressive disorder (MDD) is a highly burdensome health condition, for which there are numerous accepted pharmacological and psychological interventions. Adjunctive treatment (augmentation/combination) is recommended for the ~50% of MDD patients who do not adequately respond to first-line treatment. We aimed to evaluate the current evidence for concomitant approaches for people with early-stage treatment-resistant depression (TRD; defined below).

Patient perspectives of lithium and quetiapine augmentation treatment in treatment-resistant depression: A qualitative assessment.

Background: Treatment-resistant depression (TRD) has a profound cost to patients and healthcare services worldwide. Pharmacological augmentation is one therapeutic option for TRD, with lithium and quetiapine currently recommended as first-line agents. Patient opinions about pharmacological augmentation may affect treatment outcomes, yet these have not been systematically explored.

The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation.

Background: Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin's effects on cognitive function have not been widely or systematically studied.

Aim: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date.

A retrospective examination of care pathways in individuals with treatment-resistant depression.

Background: Individuals with treatment-resistant depression (TRD) experience a high burden of illness. Current guidelines recommend a stepped care approach for treating depression, but the extent to which best-practice care pathways are adhered to is unclear.

Aims: To explore the extent and nature of 'treatment gaps' (non-adherence to stepped care pathways) experienced by a sample of patients with established TRD (non-response to two or more adequate treatments in the current depressive episode) across three cities in the UK.

Neural effects of antidepressant medication and psychological treatments: a quantitative synthesis across three meta-analyses.

Background: Influential theories predict that antidepressant medication and psychological therapies evoke distinct neural changes.

Aims: To test the convergence and divergence of antidepressant- and psychotherapy-evoked neural changes, and their overlap with the brain's affect network.

Method: We employed a quantitative synthesis of three meta-analyses (n = 4206).

Inflammatory Proteins and Clinical Response to Psychological Therapy in Patients with Depression: An Exploratory Study.

In people with depression, immune dysfunctions have been linked with treatment non-response, but examinations of psychological therapy outcomes, particularly longitudinal biomarker studies, are rare. This study investigated relationships between inflammation, depressive subtypes and clinical outcomes to psychological therapy. Adults with depression ( = 96) were assessed before and after a course of naturalistically-delivered psychological therapy.

Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis.

Most interventions for treatment-resistant depression (TRD) are added as augmenters. We aimed to determine the relative effectiveness of augmentation treatments for TRD. This systematic review and network meta-analysis (NMA) sought all randomized trials of pharmacological and psychological augmentation interventions for adults meeting the most common clinical criteria for TRD.

Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines.

Background: Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression. A range of guidelines provide advice on treatment selection, prescription, monitoring and discontinuation, but variation in the content and quality of guidelines may limit the provision of objective, evidence-based care. This is of importance given the side effect burden and poorer long-term outcomes associated with polypharmacy and treatment-resistant depression.

Online mood monitoring in treatment-resistant depression: qualitative study of patients' perspectives in the NHS.

Aims And Method: True Colours is an automated symptom monitoring programme used by National Health Service psychiatric services. This study explored whether patients with unipolar treatment-resistant depression (TRD) found this a useful addition to their treatment regimes. Semi-structured qualitative interviews were conducted with 21 patients with TRD, who had engaged in True Colours monitoring as part of the Lithium versus Quetiapine in Depression study.

Predictors of response to augmentation treatment in patients with treatment-resistant depression: A systematic review.

Background: Treatment-resistant depression is an important contributor to the global burden of depression. Antidepressant augmentation is a recommended treatment strategy for treatment-resistant patients, but outcomes remain poor. Identifying factors that are predictive of response to augmentation treatments may improve outcomes.

Brain activation during human defensive behaviour: A systematic review and preliminary meta-analysis.

The neural underpinnings of defensive behaviour have implications for both basic research and clinical translation. This review systematically collates published research on neural response during simple avoidance of threat and approach-avoidance behaviour during goal-conflicting situations and presents an exploratory meta-analysis of available whole-brain data. Scopus, PsychInfo and Web of Science databases were searched for the period up to March 2018.

Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis.

Background: Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.AimsWe conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD.

Meta-analyses of the neural mechanisms and predictors of response to psychotherapy in depression and anxiety.

Understanding the neural mechanisms underlying psychological therapy could aid understanding of recovery processes and help target treatments. The dual-process model hypothesises that psychological therapy is associated with increased emotional-regulation in prefrontal brain regions and decreased implicit emotional-reactivity in limbic regions; however, research has yielded inconsistent findings. Meta-analyses of brain activity changes accompanying psychological therapy (22 studies, n = 352) and neural predictors of symptomatic improvement (11 studies, n = 293) in depression and anxiety were conducted using seed-based d mapping.

A morphometric signature of depressive symptoms in unmedicated patients with mood disorders.

Objective: A growing literature indicates that unipolar depression and bipolar depression are associated with alterations in grey matter volume. However, it is unclear to what degree these patterns of morphometric change reflect symptom dimensions. Here, we aimed to predict depressive symptoms and hypomanic symptoms based on patterns of grey matter volume using machine learning.