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...
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...
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...
This thesis explores the use of ketamine in people with treatment-resistant depression. It starts by examining the concept of treatment-resistant depression, a term that is widely used but poorly defined. Importantly, this label may negatively influence patients’ expectations and sense of hope. As an alternative, more neutral framing is suggested.Survey data from individuals seeking ketamine...
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...
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...
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...
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),...
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...
About one-third of patients with depression do not achieve adequate response to current treatment options. Although intravenous and intranasal administrations of (es)ketamine have shown antidepressant properties, their accessibility and scalability are limited. We investigated the efficacy, safety, and tolerability of generic oral esketamine in patients with treatment-resistant depression (TRD)...
Ketamine and its enantiomers are widely researched and increasingly used to treat mental disorders, especially treatment-resistant depression. The phenomenology of ketamine-induced experiences and their relation to its psychotherapeutic potential have not yet been systematically investigated. To describe the phenomenology of patient experiences during oral esketamine treatment for...
Introduction: Ketamine and its S-enantiomer esketamine are novel pharmacotherapeutic options for treatment resistant depression (TRD). There is growing evidence on the efficacy for other psychiatric disorders, including posttraumatic stress disorder (PTSD). It is hypothesized that psychotherapy may further potentiate the effects of (es)ketamine in psychiatric disorders. Methods: Repeated oral...
Ketamine has rapid yet often transient antidepressant effects in patients with treatment-resistant depression. Different strategies have been proposed to prolong these effects. Maintenance ketamine treatment appears promising, but little is known about its efficacy, safety, and tolerability in depression. We searched Pubmed, Embase, and the Cochrane Library and identified three randomised...
Objective: Ketamine is increasingly prescribed for treatment-resistant depression (TRD), often as add-on to regular antidepressants. Augmentation of ketamine to monoamine oxidase inhibitors (MAOIs) is advised against, as this practice might increase blood pressure or cause serotonin syndrome. Despite the potential relevance for patients, little is known about actual side effects of combined...
Ketamine and its enantiomer esketamine represent promising new treatments for treatment-resistant depression (TRD). Esketamine induces acute, transient psychoactive effects. How patients perceive esketamine treatment, and which conditions facilitate optimal outcomes, remains poorly understood. Understanding patient perspectives on these phenomena is important to identify unmet needs, which can...
Terminally ill patients may experience existential distress, depression, or anxiety, limiting quality of life in the final stage. Existing psychotherapeutic or pharmacological interventions have (time) limited efficacy. Psychedelic treatment may be a safe and effective alternative treatment option. Systematically review studies on psychedelic treatment with and without psychotherapy for...
Objective: Ketamine shows rapid and robust antidepressant effects in clinical studies. Psychotic features are an exclusion criterion in most ketamine treatment studies based on the assumption that psychosis will increase with ketamine administration. As patients with treatment-resistant depression (TRD) often have psychotic features, and treatment-resistant depressive symptoms are also common...
Abstract Background The use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as an add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review, we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine...
There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine's...
BACKGROUND: Off-label ketamine treatment has shown acute antidepressant effects that offer hope for patients with therapy-resistant depression. However, its potential for integration into treatment algorithms is controversial, not least because the evidence base for maintenance treatment with repeated ketamine administration is currently weak. Ketamine is also a drug of misuse, which has raised...