Fundamental & clinical pharmacology
July 1, 2026
Nina Abukahok, Steven Lawrence, Samrachana Adhikari et al.
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...
FOCUS The Journal of Lifelong Learning in Psychiatry
July 1, 2026
Morgan S. Hardy, S. William Li, Samuel T. Wilkinson
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...
The Journal of Clinical Psychiatry
May 4, 2026
Samuel T. Wilkinson, Brandon Kitay, Matthew Macaluso et al.
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:...
April 21, 2026
Samuel T. Wilkinson
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...
April 21, 2026
Samuel T. Wilkinson
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...
April 21, 2026
Samuel T. Wilkinson
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...
Focus (American Psychiatric Publishing)
April 1, 2026
Naim Zaki, Li Nancy Chen, Rosanne Lane et al.
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...
Contemp Clin Trials
March 2, 2026
Samuel T. Wilkinson, Sandhya Prashad, Rachel Dalthorp et al.
1 citation
Non-inferiority, comparative effectiveness study of intravenous ketamine v. intranasal esketamine for treatment-resistant depression: The EQUIVALENCE trial protocol.
American Journal of Psychiatry
September 10, 2025
Songze Li, Kristina T. Kumpf, Julian Urrutia et al.
13 citations
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...
The Journal of Clinical Psychiatry
September 3, 2025
Kristina T. Kumpf, Samuel T. Wilkinson, Bo Hu et al.
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 International Journal of Neuropsychopharmacology
June 6, 2025
Naim Zaki, Li Nancy Chen, Rosanne Lane et al.
32 citations
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,...
Psychiatry Research
May 1, 2025
Gerard Sanacora, Brian S. Barnett, Bo Hu et al.
2 citations
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)...
JAMA Psychiatry
April 16, 2025
Samuel T. Wilkinson, Gerard Sanacora
14 citations
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.
The Journal of Clinical Psychiatry
October 2, 2024
Mia C Santucci, Mina Ansari, Sina Nikayin et al.
12 citations
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...
JAMA Network Open
June 3, 2024
Manish Kumar Jha, Samuel T. Wilkinson, Kamini Krishnan et al.
29 citations
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...
JAMA Psychiatry
January 3, 2024
Samuel T. Wilkinson, Joseph J Palamar, Gerard Sanacora
41 citations
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.
General Hospital Psychiatry
2024
Mina Ansari, Brian Pittman, Daniel S Tylee et al.
6 citations
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...
Drug Discovery Today
December 1, 2023
Taeho Greg Rhee, Pasha A. Davoudian, Gerard Sanacora et al.
20 citations
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),...
Proceedings of the National Academy of Sciences of the United States of America
November 27, 2023
John H. Krystal, Alfred P. Kaye, Sarah J. Jefferson et al.
66 citations
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...
Neuropsychopharmacology
May 12, 2023
Naim Zaki, Li Chen, Rosanne Lane et al.
122 citations
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...
Psychiatry Research
March 15, 2023
Ibrahim Turkoz, J. Craig Nelson, Samuel T. Wilkinson et al.
19 citations
This exploratory post hoc analysis of two pooled 4-week, phase 3, double-blind, placebo- and active-controlled studies that compared esketamine nasal spray plus a newly initiated oral antidepressant (ESK+AD; n = 310) with a newly initiated oral AD plus placebo nasal spray (AD+PBO; n = 208) in patients with treatment-resistant depression (TRD) examined baseline patient demographic and...
Molecular Psychiatry
September 7, 2022
Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al.
80 citations
Abstract Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar...
JAMA Psychiatry
May 11, 2022
Sina Nikayin, Taeho Greg Rhee, Maria Elena Cunningham et al.
43 citations
This comparative analysis examines the trajectory of depression severity among patients treated with intravenous ketamine or intranasal esketamine in a clinical setting.
Expert Opinion on Drug Safety
April 13, 2022
Sina Nikayin, Eva Murphy, John H. Krystal et al.
114 citations
INTRODUCTION: Ketamine can produce rapid-acting antidepressant effects. Esketamine (Spravato), the S-enantiomer of racemic ketamine, was approved by the FDA for treatment-resistant depression in 2019. Here we review what is known about the long-term safety of both racemic ketamine and esketamine as therapies for psychiatric disorders. AREAS COVERED: In this article, we conducted a safety review...
The Journal of Clinical Psychiatry
July 16, 2021
Ibrahim Turkoz, Ella Daly, Jaskaran Singh et al.
21 citations
) and treatment-resistant depression (TRD) who did not meet response criteria within the first week of treatment. The current study is a pooled post hoc analysis of two phase 3, double-blind, active-controlled studies, conducted between August 2015 and February 2018, comparing ESK + AD with an oral antidepressant plus placebo (AD + PBO). Early treatment response was defined as a ≥ 50% decrease...