Samuel Wilkinson, MD
Cards
Appointments
Titles
Associate Director, Yale Depression Research Program, Psychiatry
Contact Info
Appointments
Titles
Associate Director, Yale Depression Research Program, Psychiatry
Contact Info
Appointments
Titles
Associate Director, Yale Depression Research Program, Psychiatry
Contact Info
About
Titles
Associate Professor of Psychiatry
Associate Director, Yale Depression Research Program, PsychiatryAppointments
Psychiatry
Associate Professor on TermPrimary
Other Departments & Organizations
- Center for Brain & Mind Health
- Interventional Psychiatry Service
- Neuroscience Research Training Program (NRTP)
- Psychiatry
- Yale Depression Research Program
- Yale Medicine
Education & Training
- Resident
- Yale School of Medicine (2016) (2016)
- MD
- Johns Hopkins University School of Medicine (2012)
- BS
- Brigham Young University, Mechanical Engineering (2008)
Research
Overview
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 is 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 treatment 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.
Research at a Glance
Yale Co-Authors
Publications Timeline
Gerard Sanacora, PhD, MD
Robert Ostroff, MD
John Krystal, MD
Michael Bloch, MD, MS
Rachel Katz, MD, BS
Sina Nikayin, MD
Publications
2024
Blood pressure changes during ketamine infusion for the treatment of depression
Ansari M, Pittman B, Tylee D, Ostroff R, Wilkinson S, Nikayin S. Blood pressure changes during ketamine infusion for the treatment of depression. General Hospital Psychiatry 2024, 90: 62-67. PMID: 38991311, DOI: 10.1016/j.genhosppsych.2024.07.001.Peer-Reviewed Original ResearchConceptsKetamine infusionBlood pressure changesBlood pressureRetrospective chart review of patientsChart review of patientsMedical history of hypertensionRetrospective chart reviewHistory of hypertensionSignificant blood pressureDiastolic blood pressureTreatment of depressionSevere hypertensionPatient demographicsHypertensive patientsInfusion sessionsMedical historyHypertensive eventsInfusionPatientsKetamineBP surgeCardiovascular monitoringBloodHypertensionPressure changesKetamine vs Electroconvulsive Therapy for Treatment-Resistant Depression
Jha M, Wilkinson S, Krishnan K, Collins K, Sanacora G, Murrough J, Goes F, Altinay M, Aloysi A, Asghar-Ali A, Barnett B, Chang L, Costi S, Malone D, Nikayin S, Nissen S, Ostroff R, Reti I, Wolski K, Wang D, Hu B, Mathew S, Anand A. Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression. JAMA Network Open 2024, 7: e2417786. PMID: 38916891, PMCID: PMC11200139, DOI: 10.1001/jamanetworkopen.2024.17786.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsTreatment-resistant depressionQIDS-SR16 scoresElectroconvulsive therapy groupElectroconvulsive therapyQIDS-SR16Measure of premorbid intelligencePosttraumatic stress disorder diagnosisTrial of electroconvulsive therapyNonpsychotic depressive episodeImpaired memory recallAssociated with differential improvementStress disorder diagnosisIntravenous ketamineEnd-of-treatment visitInfusion of ketamineMADRS scorePremorbid intelligenceResistant depressionDepressive episodeMeasures mixed-effects modelsFalse discovery rate adjustmentDisorder diagnosisMemory recallSevere depressionDifferential improvementThe Rapidly Shifting Ketamine Landscape in the US
Wilkinson S, Palamar J, Sanacora G. The Rapidly Shifting Ketamine Landscape in the US. JAMA Psychiatry 2024, 81: 221-222. PMID: 38170542, DOI: 10.1001/jamapsychiatry.2023.4945.Peer-Reviewed Original ResearchCitationsAltmetric
2023
Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments
Krystal J, Kaye A, Jefferson S, Girgenti M, Wilkinson S, Sanacora G, Esterlis I. Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2305772120. PMID: 38011560, PMCID: PMC10710048, DOI: 10.1073/pnas.2305772120.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsPsychedelic renaissance: Revitalized potential therapies for psychiatric disorders
Rhee T, Davoudian P, Sanacora G, Wilkinson S. Psychedelic renaissance: Revitalized potential therapies for psychiatric disorders. Drug Discovery Today 2023, 28: 103818. PMID: 37925136, DOI: 10.1016/j.drudis.2023.103818.Peer-Reviewed Original ResearchAltmetricConceptsPsychiatric disordersLysergic acid diethylamideClinical trialsUS Clinical Trials RegistryClinical Trials RegistryPotential therapeutic effectsTrials RegistryTherapeutic effectPotential therapyTherapeutic agentsN-dimethyltryptamineAcid diethylamideLargest causePsychedelic compoundsDisordersPsychotherapeutic approachesSafety concernsTrialsPotential interactive effectsCutting-edge reviewPsychedelic substancesRegistryTherapyCognitive behavioral therapy following esketamine for major depression and suicidal ideation for relapse prevention: The CBT-ENDURE randomized clinical trial study protocol
Kitay B, Murphy E, Macaluso M, Corlett P, Hershenberg R, Joormann J, Martinez-Kaigi V, Nikayin S, Rhee T, Sanacora G, Shelton R, Thase M, Wilkinson S. Cognitive behavioral therapy following esketamine for major depression and suicidal ideation for relapse prevention: The CBT-ENDURE randomized clinical trial study protocol. Psychiatry Research 2023, 330: 115585. PMID: 37935086, DOI: 10.1016/j.psychres.2023.115585.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsCognitive behavioral therapyMajor depressionSuicidal ideationRelapse preventionBehavioral therapyStudy protocolHigh riskClinical trial study protocolLong-term treatment approachKey secondary outcomesTrial study protocolHigh relapse rateHigh-risk populationSignificant suicidal ideationHospital dischargeSecondary outcomesPrimary outcomeRelapse rateFeasibility trialEsketamineTreatment approachesPatientsSuicide attemptsTherapySupplemental indicationsEfficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study
Castro M, Wilkinson S, Al Jurdi R, Petrillo M, Zaki N, Borentain S, Fu D, Turkoz I, Sun L, Brown B, Cabrera P. Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study. CNS Drugs 2023, 37: 715-723. PMID: 37558912, PMCID: PMC10439056, DOI: 10.1007/s40263-023-01026-3.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsEsketamine nasal spraySUSTAIN 1Nasal spraySecond inductionMaintenance treatmentMADRS response ratesTreatment-emergent AEsDepression rating scoresNew safety signalsTreatment-resistant depressionTime of relapseLong-term treatmentLong-term trialsEligible patientsOral antidepressantsRemission rateStable remissionSubgroup analysisChronic illnessSafety signalsInterim analysisDepressive symptomsPatientsResponse rateRemissionTrends in Illicit Ketamine Seizures in the US From 2017 to 2022
Palamar J, Wilkinson S, Carr T, Rutherford C, Cottler L. Trends in Illicit Ketamine Seizures in the US From 2017 to 2022. JAMA Psychiatry 2023, 80: 750-751. PMID: 37223891, PMCID: PMC10209822, DOI: 10.1001/jamapsychiatry.2023.1423.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsKetamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression
Anand A, Mathew S, Sanacora G, Murrough J, Goes F, Altinay M, Aloysi A, Asghar-Ali A, Barnett B, Chang L, Collins K, Costi S, Iqbal S, Jha M, Krishnan K, Malone D, Nikayin S, Nissen S, Ostroff R, Reti I, Wilkinson S, Wolski K, Hu B. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. New England Journal Of Medicine 2023, 388: 2315-2325. PMID: 37224232, DOI: 10.1056/nejmoa2302399.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsTreatment-resistant major depressionPatient-reported qualityElectroconvulsive therapyMajor depressionECT groupKetamine groupTreatment phaseMusculoskeletal adverse effectsSubanesthetic intravenous ketamineWeeks of treatmentInitial treatment phaseIntravenous ketamineSecondary outcomesPrimary outcomeNoninferiority marginTrial groupECT clinicsNoninferiority trialPatientsComparative effectivenessKetamineClinical sitesAdverse effectsDepressionThree timesLong-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study
Zaki N, Chen L, Lane R, Doherty T, Drevets W, Morrison R, Sanacora G, Wilkinson S, Popova V, Fu D. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study. Neuropsychopharmacology 2023, 48: 1225-1233. PMID: 37173512, PMCID: PMC10267177, DOI: 10.1038/s41386-023-01577-5.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsTreatment-resistant depressionEsketamine treatmentMontgomery-Åsberg Depression Rating Scale (MADRS) total scoreCommon treatment-emergent adverse eventsLong-term extension studyTreatment-emergent adverse eventsEsketamine nasal sprayMean cumulative durationLong-term tolerabilityNew safety signalsHealth-related qualityMaintenance of responseLong-term treatmentMajor depressive disorderLong-term safetyPhase 3Scale total scoreMaintenance phaseOral antidepressantsData cutoffAdverse eventsMaintenance treatmentSustained efficacyEligible participantsDepression ratings
Academic Achievements and Community Involvement
honor New Investigator Award
International AwardInternational Society of CNS Clinical Trials MethodologyDetails01/01/2019United Stateshonor Career Development Leadership Program Award
International AwardAnxiety and Depression Associations of AmericaDetails04/05/2018United Stateshonor Top Advancements & Breakthroughs for 2017
International AwardBrain and Behavior Research Foundation (formerly NARSAD)Details12/15/2017United Stateshonor Mentored Clinical Research Award
Regional AwardRobert E. Leet and Clara Guthrie Patterson TrustDetails02/15/2017United Stateshonor NARSAD Young Investigator Award
National AwardBrain and Behavior Research FoundationDetails01/01/2017United States
Links & Media
News
- April 03, 2024Source: Psychology Today
What I Want My Patients to Know: Ketamine for Depression
- March 05, 2024Source: YaleNews
What Is Life’s Purpose? A Yale Psychiatrist Looks to Science for Answers
- March 05, 2024
Searching Science for Life's Purpose
- March 05, 2024Source: Time
The Problem With Our Need to Achieve