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Samuel T Wilkinson

Yale Depression Research Program, Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. Electronic address: samuel.wilkinson@yale.edu.

9 papers in the library · 181 citations · publishing 2022-2026

Papers

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators

Molecular Psychiatry September 7, 2022 Rebecca B Price, Nicholas Kissel, Andrew Baumeister et al. 80 citations

Ketamine given intravenously rapidly reduces depressive symptoms, with effects lasting at least a week. In an analysis of 17 randomized controlled trials with 809 participants, the benefit over placebo was larger for patients who had already failed two or more prior antidepressant trials. However, no patient-level clinical or demographic characteristics—such as age, sex, or diagnosis—could predict who would respond best, limiting the ability to personalize ketamine prescriptions. The findings confirm ketamine's broad effectiveness for depression but show that precision medicine approaches cannot yet guide treatment decisions.

Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study.

The international journal of neuropsychopharmacology June 6, 2025 Naim Zaki, Li Nancy Chen, Rosanne Lane et al. 32 citations

In a long-term extension study (SUSTAIN-3) involving 1,148 adults with treatment-resistant depression, esketamine nasal spray combined with an oral antidepressant was evaluated for safety and efficacy over up to 79 months (median 45.8 months). Common adverse events included headache (36.9%), dizziness (33.9%), and nausea (33.6%). Nine participants died, with causes including COVID-19 and suicide. Depressive symptoms, measured by the MADRS, improved during the initial induction phase (average reduction of 12.8 points) and this improvement was maintained during the optimization/maintenance phase. At the end of maintenance, 49.6% of participants were in remission. No new safety concerns emerged, and depression improvement generally persisted for those continuing treatment.

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial.

JAMA network open June 3, 2024 Manish Kumar Jha, Samuel T Wilkinson, Kamini Krishnan et al. 29 citations

In people with treatment-resistant depression who do not have psychosis, intravenous ketamine works as well as electroconvulsive therapy (ECT) overall. Among outpatients with moderately severe or severe depression, ketamine produced greater improvement in depressive symptoms than ECT. In contrast, inpatients with very severe depression improved more with ECT early in treatment, though by the end of the three-week course both treatments were similarly effective. Higher premorbid intelligence and a diagnosis of posttraumatic stress disorder were linked to greater improvement with ECT, but not with ketamine. These findings may help patients and clinicians decide between the two treatments.

Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders.

Drug discovery today December 1, 2023 Taeho Greg Rhee, Pasha A Davoudian, Gerard Sanacora et al. 20 citations

Psychiatric disorders are the leading cause of disability globally, and interest in psychedelic substances as potential treatments has recently revived. This review examines the therapeutic potential and safety concerns of psilocybin, DMT, LSD, and MDMA, including their possible interactions with psychotherapy. It covers active and recently completed clinical trials drawn from published literature, conference abstracts, clinical trial registries, and press releases. The review suggests that these compounds may offer new avenues for treating psychiatric disorders, though safety considerations remain important.

Efficacy and Safety of Ketamine/Esketamine in Bipolar Depression in a Clinical Setting.

The Journal of clinical psychiatry October 2, 2024 Mia C Santucci, Mina Ansari, Sina Nikayin et al. 12 citations

In a real-world clinical setting, 45 patients with treatment-resistant bipolar depression received intravenous ketamine or intranasal esketamine. Among 38 who completed an acute series (twice-weekly treatments for up to four weeks), 39% achieved a clinical response (at least 50% improvement on the Montgomery-Asberg Depression Rating Scale) and 13.2% achieved remission (score of 10 or lower). Mean depression scores dropped from 31.1 to 19.2, a 38.3% improvement. No manic or hypomanic episodes occurred during the acute phase. However, during maintenance treatment, 28.9% of patients experienced hypomanic or manic symptoms, with one severe event requiring hospitalization.

Blood pressure changes during ketamine infusion for the treatment of depression.

General hospital psychiatry January 1, 2024 Mina Ansari, Brian Pittman, Daniel S Tylee et al. 6 citations

Blood pressure increases during ketamine infusion for depression, peaking at 40 minutes with average rises of 16.0 mmHg systolic and 11.0 mmHg diastolic. Severe hypertension occurred in 12.5% of patients and 0.98% of infusion sessions, most often during the first three treatments. Older age and a history of hypertension were associated with larger blood pressure surges, indicating that careful cardiovascular monitoring is needed, especially for these patients.

Patient preference effects in a randomized comparative effectiveness study of electroconvulsive therapy and ketamine for treatment resistant depression: An ELEKT-D trial secondary analysis.

Psychiatry research May 1, 2025 Gerard Sanacora, Brian S Barnett, Bo Hu et al. 2 citations

Patients with treatment-resistant depression who preferred ketamine over electroconvulsive therapy (ECT) were more likely to respond to treatment, regardless of which treatment they actually received. Matching patients to their preferred treatment improved response rates for ketamine but not for ECT, and reduced adverse events for ECT-treated patients. Ketamine was the more popular choice overall. The findings suggest that aligning treatment with patient preference can influence effectiveness, safety, and possibly adherence, but these effects vary by treatment modality and context.

Monitoring of Clinics That Use Direct-to-Consumer Advertising for Off-Label Ketamine in the New York Metropolitan Area: A Cross-Sectional Systematic Web Search.

Fundamental & clinical pharmacology July 1, 2026 Nina Abukahok, Steven Lawrence, Samrachana Adhikari et al.

In the New York metropolitan area, over a third of clinics advertising ketamine for psychiatric conditions offer it for at-home use, raising safety concerns. A 2025 systematic web search identified 233 clinics; 36.5% prescribed ketamine for at-home use, 51.5% listed a medical doctor, 42.9% advertised oral ketamine, and depression was the most common condition treated (94.0%). Clinics advertising oral ketamine were over four times more likely to offer at-home use, while those listing a medical doctor were about half as likely. The findings suggest a consumer-oriented advertising approach that may warrant monitoring and clearer guidance to mitigate safety risks.

Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention: The CBT-ENDURE Randomized Trial.

The Journal of clinical psychiatry May 4, 2026 Samuel T Wilkinson, Brandon M Kitay, Matthew Macaluso et al.

Adding cognitive behavioral therapy to esketamine treatment reduces suicidal ideation more than esketamine alone in people with major depression and suicidal thoughts. In a randomized trial of 93 patients, 72% completed the study, meeting feasibility goals. Those who received 16 weeks of CBT plus esketamine showed greater improvement on three measures of suicidal ideation than those receiving esketamine with usual care: a mean difference of -1.91 on the Beck Scale for Suicidal Ideation, -0.33 on the Clinician Global Improvement Scale for Suicide Severity, and -3.77 on the depression rating scale. No difference was found on the Columbia-Suicide Severity Rating Scale or in suicide-related events.