Samuel Wilkinson, MD

Clinician; Assistant Director, Yale Depression Research Program

Research Organizations

Yale Depression Research Program

Research Summary

I have research interests in treatment-resistant depression, including ketamine, electroconvulsive therapy (ECT). I have an interest in the potential therapeutic as well as adverse effects of cannabinoids.

Extensive Research Description

1. I have an interest in improving access to and dissemination of preventive measures and evidence-based therapies for depression and other mood disorders. In particular, I am interested in improving the quality and safety of and access to evidenced-based therapies for severe and treatment-resistant depression, which accounts for a disproportionate fraction of the morbidity associated with depression generally. Some of my work thus far relates to the use of electroconvulsive therapy (ECT), which is the most-effective treatment for severe depression. In particular, I have focused on developing and testing relapse prevention strategies that are scalable and would improve the quality and dissemination of these treatments. In this context, I am also interested in partnering with patient stakeholders to design studies that will be of most benefit clinically to patients (patient-centered outcomes research). 

2. A promising treatment for severe depression is the intravenous use of sub-anesthetic doses of ketamine. Yet high rates of relapse following treatment precludes broader dissemination of a potentially powerful intervention for patients. My current work examines the potential of cognitive behavioral therapy (CBT) as a relapse prevention strategy following ketamine. This is based on the hypothesis that there is a period of enhanced neuroplasticity following ketamine exposure that may present an opportune time for cognitive and behavioral interventions to harness this enhanced neuroplasticity. The combination of CBT following ketamine may improve longer-term outcomes while at the same time limiting indefinite exposure to ketamine, which of potential concern. I am also interested in the way that community practitioners and academic sites have adopted ketamine as an off-label treatment for mood disorders and in the development of reasonable practice standards for this emerging treatments which should engender both hope but also caution as it is implemented. 

3. Finally, an early research interest was in the rapidly changing legal status of cannabis, including its approval as “medicine” on a state-level despite little evidence examining efficacy or safety in many conditions. One of my works showed that marijuana use was associated with worse outcomes among patients with posttraumatic stress disorder (PTSD), despite the fact that PTSD is an “approved indication” for medical marijuana in many states. 


Selected Publications

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Samuel Wilkinson, MD