Antidepressant treatments, including conventional antidepressants and (es)ketamine, may reverse default mode network (DMN) resting-state functional connectivity (rsFC) alterations related to major depressive disorder (MDD). Despite these agents having distinct initial action mechanisms, both likely share downstream effects that lead to structural and functional adaptations in MDD-related neural...
The contribution of patient support to psilocybin's antidepressant effects remains uncertain. Relationships between therapeutic alliance (Scale to Assess Therapeutic Relationship-Patient version; STAR-P), psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire and Emotional Breakthrough Inventory; 5D-ASC and EBI) and clinical outcomes (Montgomery-Åsberg Depression...
Ketamine and its enantiomer esketamine are efficacious in 30-35% of the patients with treatment-resistant depression (TRD). Increased serum brain-derived neurotrophic factor (BDNF) following treatment has been proposed as a potential biomarker of antidepressant response. This is based on studies evaluating single intravenous ketamine treatment. BDNF expression at different treatment schedules...
The research, understanding, and implementation of psychedelic therapies is characterised by a layered complexity that arises from the dynamic interactions between pharmacological and extra-pharmacological factors, and the embeddedness of psychedelics within broader societal, legal, and regulatory systems ill-equipped to accommodate them. This complexity is compounded by an epistemic...
Psychedelic-assisted therapy (PAT) is increasingly recognized as a potential novel treatment for substance use disorder (SUD). As evidence continues to grow, the successful implementation of this modality into clinical practice will depend significantly on the perceptions and attitudes of mental healthcare professionals. Accordingly, a systematic review was conducted to provide a comprehensive...
Oral esketamine is a potentially effective and well-tolerated treatment for treatment-resistant depression (TRD). However, around 50% of TRD individuals treated with oral esketamine do not achieve response, and this variation in response may be accounted for by interindividual differences between patients. Efforts to develop effective and personalized depression treatment strategies are...
Ketamine, including its enantiomers (S)-ketamine (esketamine) and (R)-ketamine (arketamine), has demonstrated rapid antidepressant effects in major depressive disorder (MDD) and bipolar disorder (BD), yet clinical responses vary widely, highlighting the need to identify mechanisms underlying treatment efficacy and related potential predictors. Growing evidence suggests that alterations in sleep...
Summary This case report presents the case of a 25-year-old woman who developed ketamine addiction following a single sub-anaesthetic dose of intranasal ketamine in a pilot study investigating intranasal racemic ketamine for acute suicidality. She had a history of depression, obsessive–compulsive disorder, autism spectrum disorder and anorexia nervosa, and she had sporadically used alcohol and...
Oral esketamine displays therapeutic potential for treatment-resistant depression. However, treatment is complicated by a low and variable bioavailability. Genetic polymorphisms in the cytochrome P450 (CYP) enzymes responsible for esketamine's metabolism may influence bioavailability. In a subsample of patients included in a placebo-controlled trial investigating repeated, low dose oral...
Ketamine has been shown to decrease suicidality in patients with depression. However, little is known about tolerability and efficacy in heterogenous, acutely suicidal patients in emergency settings. This pilot study aimed to assess the feasibility, acceptability, and safety of generic intranasal racemic ketamine (75 mg) in the treatment of acute suicidality regardless of the underlying...
Ketamine-assisted psychotherapy (KAP) is considered a promising treatment strategy in psychiatric disorders, combining psychotherapeutic interventions with the rapid-acting pharmacological effects of ketamine towards enhancing outcomes. Although KAP has been practiced for many years across different diagnoses, evidence regarding optimal treatment methods and working mechanisms remains limited...
Oral esketamine is a promising new therapy for treatment-resistant depression. However, concerns exist about interindividual pharmacokinetic variability. Genetic polymorphisms regulating the expression of ATP-binding cassette (ABC) transporters might influence bioavailability. Utilizing blood samples from a placebo-controlled trial investigating repeated, low dose oral esketamine (N = 18), we...
Suicidality is a transdiagnostic entity in patients with and without psychiatric disorders. Ketamine is a novel treatment for treatment-resistant depression with favorable effects on related suicidality in this population. Little is known about the effects of ketamine on suicidality as a distinct phenomenon. To assess whether a dose of 75 mg intranasal (IN) ketamine reduces acute suicidality...
Classic psychedelics are increasingly studied as potential treatments for different psychiatric disorders. Current research protocols often require patients to discontinue antidepressants (ADs) for at least 2 weeks before psychedelic administration to decrease the risk of serotonin syndrome and limit their effect on efficacy and the acute subjective effects of psychedelics. Moreover, the...
Intranasal (IN) esketamine represents a novel add-on treatment for treatment-resistant depression (TRD) with reported favourable effects on insomnia. IN esketamine treatment might similarly reduce the incidence of insomnia as an adverse event (AE). The present meta-analysis therefore investigated whether IN esketamine relative to placebo is associated with a lower incidence of insomnia as an AE...
Oral esketamine has relatively low and variable bioavailability, which may complicate broader use as an antidepressant. This study aimed to investigate associations between different pharmacokinetic outcomes and change in depressive symptoms following oral esketamine administration in patients with treatment-resistant depression. Understanding such associations may inform dosing and...
Oral esketamine for patients with treatment-resistant depression (TRD) could offer certain advantages over other routes, such as intravenous or intranasal, but it has not been systematically studied in a real-world setting. Here we present results from a relatively large naturalistic study to evaluate the effectiveness, tolerability, and safety of oral esketamine in patients with TRD. One...
Background: Esketamine is a rapidly acting antidepressant with robust efficacy in treatment-resistant depression (TRD). Diminishing therapeutic effects and attenuated side effects have been reported after long-term use. This study aimed to investigate its long-term pharmacokinetics and factors that may contribute to reduced efficacy over time in patients with TRD by evaluating the potential...
To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression. 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...
Accumulating evidence supports the efficacy of (es)ketamine in the treatment of major depressive disorder (MDD), particularly treatment-resistant depression (TRD). Yet around 50% of the individuals with TRD do not respond to (es)ketamine. Elucidating predictors of response and remission could improve treatment outcomes at the individual level by defining subpopulations that are most likely to...
This study investigates repeated oral esketamine as a substitution strategy for maintenance electroconvulsive therapy (M-ECT) in eight patients with treatment-resistant depression (TRD). In a 6-week dosing phase, esketamine was titrated from 0.5 or 1.0 mg/kg to a maximum of 3.0 mg/kg twice weekly. Outcomes included 6-week change in Inventory of Depressive Symptomatology - Self-rated (IDS-SR),...
Psilocybin represents a novel therapeutic approach for individuals with major depressive disorder (MDD) who do not respond to conventional antidepressant treatment. Investigating the influence of psilocybin on the pathophysiological processes involved in MDD could enhance our neurobiological understanding of the presumed antidepressant action mechanism. This systematic review aims to summarize...
Although studies of psychedelic-assisted psychotherapy are accumulating, there is no consensus regarding best practice of the psychotherapeutic component. In this systematic review, we summarised the quality of reporting on psychological interventions in research about psychedelic treatments. The design followed PRISMA guidelines and was preregistered in PROSPERO (CRD42022319221). We searched...
Patients with a life-threatening disease (LTD) sometimes suffer from end-of-life distress (EOLD) which refers to the physical, psychological, emotional, and spiritual suffering related to chronic illness and the possibility of death. Palliative care interventions seek to improve the quality of life of patients with EOLD and their significant others. Currently, a range of psychological and...
Post-Traumatic Stress Disorder (PTSD) is a severe psychiatric condition that develops after exposure to trauma such as combat, natural disasters, or assault. It is characterized by re-experiencing trauma, avoidance, hyperarousal, and negative alterations in cognition and mood. Since its formal inclusion in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III in 1980, PTSD has...