Ketamine/esketamine produce rapid antidepressant effects, with growing interest in how acute subjective experiences and the surrounding set and setting shape clinical outcomes. Little is known about how audiovisual adjustments during ketamine/esketamine treatment influence comfort, tolerability, or patient experience, despite their common use in clinical practice. Virtual reality (VR) is one...
Despite the wide prevalence of mood disorders globally, there is a substantial unmet need for effective, mechanistically distinct treatments. Given that approximately 30% of individuals do not display adequate response to standard antidepressant therapies, the past 15 years have seen a shift away from traditional monoaminergic approaches toward glutamatergic and other novel mechanisms....
Ketamine is increasingly prescribed in an off-label manner to treat psychiatric disorders, raising concerns about direct-to-consumer advertising and the proliferation of clinics offering ketamine for at-home use without direct medical supervision. We aimed to identify and characterize clinics advertising ketamine for psychiatric conditions online in the New York metropolitan area (New York, New...
Over the past two decades, ketamine has emerged as a rapid-acting antidepressant, especially among patients with treatment-resistant depression. As an N-methyl-d-aspartate glutamate receptor antagonist, ketamine has reshaped the understanding of the underlying neurobiological mechanisms of depression treatment. Ketamine induces a transient state of enhanced neuroplasticity and likely...
Background: Suicide is a public health crisis in the US, with limited evidence demonstrating efficacy of treatments for high-risk patients due in part to their exclusion from most clinical trials. This clinical trial evaluates the feasibility and efficacy of adjunctive cognitive behavioral therapy (CBT) with esketamine in patients with major depression and suicidal ideation (MDSI). Methods:...
Reserve ketamine or esketamine for patients who have failed two to four adequate antidepressant trials. Weigh severity too; mild cases may not warrant it. Consider esketamine for acute suicidality in TRD despite the negative trial results. Placebo groups received excellent inpatient standard of care and improved substantially, masking the drug's benefit. Avoid ketamine and esketamine in active...
When a patient relapses after tapering off ketamine or esketamine, consider restarting an index course (twice weekly for a few weeks, then spread out). With ketamine or esketamine, dysphoric reactions occur in roughly 1 in 200-300 treatments. Many resolve with supportive care alone; others require a short-acting benzodiazepine such as lorazepam. For esketamine sessions, have patients fast for...
After completing this activity, participants should be able to: Identify appropriate candidates for ketamine or esketamine based on prior treatment failures, severity, substance use history, and relevant contraindications. Describe strategies for maintenance dosing, tapering, and managing rapid relapse after discontinuation of ketamine or esketamine. Apply clinic-based approaches to managing...
Na het voltooien van deze activiteit dienen deelnemers in staat te zijn om: Geschikte kandidaten voor ketamine of esketamine te identificeren op basis van eerdere behandelmislukkingen, ernst van de aandoening, middelengebruiksgeschiedenis en relevante contra-indicaties. Strategieën te beschrijven voor onderhoudsdosering, afbouw en het omgaan met snelle terugval na het staken van ketamine of...
Reserveer ketamine of esketamine voor patiënten bij wie twee tot vier adequate antidepressieve behandelingen onvoldoende effect hebben gehad. Weeg ook de ernst mee; bij milde gevallen is dit doorgaans niet geïndiceerd. Overweeg esketamine bij acute suïcidaliteit bij therapieresistente depressie, ondanks de negatieve studieresultaten. De placebogroepen ontvingen uitstekende intramurale...
Wanneer een patiënt terugvalt na het afbouwen van ketamine of esketamine, overweeg dan een herstart van een inductiekuur (tweemaal per week gedurende enkele weken, vervolgens geleidelijk spreiden). Bij ketamine of esketamine treden dysfore reacties op bij ongeveer 1 op de 200-300 behandelingen. Veel hiervan verdwijnen met ondersteunende zorg alleen; andere vereisen een kortwerkend...
Patients with treatment-resistant depression (TRD) have higher rates of relapse and pronounced decreases in daily functioning and health-related quality of life compared to patients with major depressive disorder who are not treatment-resistant, underscoring the need for treatment choices with sustained efficacy and long-term tolerability. Adults with TRD who participated in ≥1 of 6 phase 3...
Ketamine is a powerful and rapid-acting antidepressant but has no regulatory authorization for any psychiatric illness. The S-enantiomer of ketamine, esketamine, was approved by the FDA in 2019 as adjunctive therapy for treatment-resistant depression. Substantial controversy exists as to whether there is a significant clinical difference between intravenous (IV) ketamine racemate and intranasal...
This review examines ketamine's neurotoxic potential across preclinical and clinical studies. The authors synthesized data from preclinical models, then integrated findings from human clinical trials of esketamine and observational studies in recreational users. Animal studies have found that repeated or high-dose subanesthetic ketamine administration results in consistent excitotoxic neuronal...
Electroconvulsive therapy (ECT) has potent antidepressant effects yet can lead to neurocognitive side effects. Ketamine is a rapid-acting antidepressant, which may be an alternative to ECT. Few have directly compared the cognitive effects of ECT and ketamine treatment. We compared cognitive effects of intravenous ketamine and ECT in patients with treatment-resistant depression (TRD), collected...
The rates of relapse and suicide risk are higher in treatment-resistant depression (TRD) vs non-treatment-resistant major depressive disorder. Even among patients with TRD who initially respond, the majority (70%) relapse within 6 months. To evaluate the long-term safety and efficacy of esketamine nasal spray, combined with an oral antidepressant, in patients with TRD. Phase 3, open-label,...
Previous studies have shown patient preference can have large effects on treatment adherence and patient satisfaction. However, the direct effects of matching treatment with patient preference on efficacy and safety outcomes remain unclear. We aimed to evaluate the effects of patient preference and preference-matching on efficacy, adverse events, and adherence to electroconvulsive therapy (ECT)...
This Viewpoint explores potential justifications underlying the US Food and Drug Administration (FDA)’s rejection of methylenedioxymethamphetamine (MDMA) as a treatment for posttraumatic stress disorder, including lack of blinding and issues around the integrity of relevant clinical trials.
Background: Bipolar disorder represents a significant source of morbidity and elevated mortality risk. Ketamine has emerged as a powerful antidepressant; however, there have been few trials of ketamine in bipolar depression and no trials with esketamine in bipolar depression, and few data exist from real-world settings. Here, we report outcomes from a cohort of patients with bipolar depression...
The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD. To evaluate whether selected clinical features were associated with...
This Viewpoint discusses changes in the use of ketamine as a medical therapeutic and a recreational substance, the potential risks of use, and the need for increased research and surveillance.
This study aimed to examine blood pressure changes during ketamine infusion for depression and exploring the factors associated with these changes. This study is a retrospective chart-review of patients with depression undergoing ketamine infusion at Yale Psychiatry Hospital during a 7-year period. Blood pressure (BP) was recorded every 10 min during the infusion. Surges in systolic and...
Psychiatric disorders represent the largest cause of disability worldwide. Global interests in psychedelic substances as potentially therapeutic agents for psychiatric disorders has recently re-emerged. Here, we review progress in the development of psychedelic compounds that have potential therapeutic effects as well as the safety concerns. We include psilocybin, N,N-dimethyltryptamine (DMT),...
Ketamine has emerged as a transformative and mechanistically novel pharmacotherapy for depression. Its rapid onset of action, efficacy for treatment-resistant symptoms, and protection against relapse distinguish it from prior antidepressants. Its discovery emerged from a reconceptualization of the neurobiology of depression and, in turn, insights from the elaboration of its mechanisms of action...
Background: Treatment-resistant depression (TRD) is a chronic illness requiring long-term treatment. Esketamine nasal spray (ESK) has been studied in several long-term trials of patients with TRD, including SUSTAIN-1 (NCT02493868) and SUSTAIN-3 (NCT02782104). This subgroup analysis of SUSTAIN-3 evaluated patients with TRD who received a second induction (IND) and maintenance treatment with ESK...