2024
Ketamine 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 ResearchConceptsTreatment-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 improvement
2023
Cognitive 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 ResearchConceptsCognitive 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 ResearchConceptsEsketamine 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 ResearchKetamine 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 ResearchConceptsTreatment-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 ResearchConceptsTreatment-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 ratingsPredictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray
Turkoz I, Nelson J, Wilkinson S, Borentain S, Macaluso M, Trivedi M, Williamson D, Sheehan J, Salvadore G, Singh J, Daly E. Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray. Psychiatry Research 2023, 323: 115165. PMID: 37019044, DOI: 10.1016/j.psychres.2023.115165.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionEsketamine nasal sprayNasal sprayDay 28Day 8Clinical Global Impression-Severity scoreCGI-S scoresCurrent depressive episodePredictors of responsePlacebo nasal sprayIdentification of predictorsOral antidepressantsBaseline patientAcute trialPooled analysisDepressive episodeRemissionPsychiatric characteristicsPatientsSignificant anxietyYounger ageTreatment assignmentPotential predictorsPhase 3PredictorsThe Role of Psychotherapy in the Management of Treatment-Resistant Depression
Rogan T, Wilkinson S. The Role of Psychotherapy in the Management of Treatment-Resistant Depression. Psychiatric Clinics Of North America 2023, 46: 349-358. PMID: 37149349, DOI: 10.1016/j.psc.2023.02.006.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionRole of psychotherapySomatic therapiesLong-term outcomesPositive therapeutic benefitsPsychotherapy modalitiesRandomized trialsMood disordersTherapeutic benefitNeural plasticityTherapyMore trialsForms of psychotherapyTrialsDepressionLess evidenceModalitiesPsychotherapy approachesPsychotherapyPotential combinationsEffects of Electroconvulsive Therapy on Functional Outcomes Among Medicare Patients With Comorbid Depression and Dementia: A Nationwide 1-Year Follow-Up Study.
Wilkinson S, Sint K, Forester B, Rhee T. Effects of Electroconvulsive Therapy on Functional Outcomes Among Medicare Patients With Comorbid Depression and Dementia: A Nationwide 1-Year Follow-Up Study. The Journal Of Clinical Psychiatry 2023, 84 PMID: 36700843, DOI: 10.4088/jcp.22m14583.Peer-Reviewed Original ResearchConceptsElectroconvulsive therapyFunctional outcomeComorbid depressionPrincipal psychiatric diagnosisRandomized clinical trialsECT cohortECT patientsComparable cohortsSafe treatmentClinical trialsMedicare patientsCurrent treatmentFunctional declineLimited efficacyPropensity score methodsPsychiatric disordersSummary scoresPsychiatric diagnosisLarger sample sizeMultivariate analysisPsychological symptomsDementiaPatientsOlder adultsCohort
2022
Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode
Rhee TG, Shim SR, Forester BP, Nierenberg AA, McIntyre RS, Papakostas GI, Krystal JH, Sanacora G, Wilkinson ST. Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode. JAMA Psychiatry 2022, 79: 1162-1172. PMID: 36260324, PMCID: PMC9582972, DOI: 10.1001/jamapsychiatry.2022.3352.Peer-Reviewed Original ResearchConceptsStandardized mean differenceMajor depressive episodeSerious adverse eventsElectroconvulsive therapyAdverse eventsDepressive episodeClinical trialsDepression severityEfficacy outcomesSystematic reviewUnique adverse effect profileMeta-analyses (PRISMA) reporting guidelinesSafety of ketamineAdverse effect profileData extractionEuropean clinical trialsDiagnosis of depressionModerate methodological qualityMedical Subject Headings termsPreferred Reporting ItemsCognition/memoryRandom-effects modelSubject Headings termsAcute phaseEffect profileInternational pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators
Price RB, Kissel N, Baumeister A, Rohac R, Woody ML, Ballard ED, Zarate CA, Deakin W, Abdallah CG, Feder A, Charney DS, Grunebaum MF, Mann JJ, Mathew SJ, Gallagher B, McLoughlin DM, Murrough JW, Muthukumaraswamy S, McMillan R, Sumner R, Papakostas G, Fava M, Hock R, Phillips JL, Blier P, Shiroma P, Šóš P, Su TP, Chen MH, Tiger M, Lundberg J, Wilkinson ST, Wallace ML. International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators. Molecular Psychiatry 2022, 27: 5096-5112. PMID: 36071111, PMCID: PMC9763119, DOI: 10.1038/s41380-022-01757-7.Peer-Reviewed Original ResearchConceptsMontgomery-Åsberg Depression Rating ScaleIndividual patient-level dataRating ScalePatient-level featuresDepression Rating ScaleHamilton Rating ScalePatient-level dataPrecision medicine approachRelevant psychiatric diagnosisEligible trialsIntravenous ketamineAntidepressant medicationStudy entryKetamine infusionPrior medicationAntidepressant propertiesKetamine effectsControl armClinical moderatorsTreatment decisionsTreatment resistanceStudy-level moderatorsDepressive symptomsPersonalized prescriptionDepression severityAt-home ketamine; still a lot to learn
Wilkinson ST, Sanacora G. At-home ketamine; still a lot to learn. Journal Of Affective Disorders 2022, 318: 150-151. PMID: 36067887, DOI: 10.1016/j.jad.2022.08.090.Peer-Reviewed Original Research
2021
Mental Health Care Resource Utilization and Barriers to Receiving Mental Health Services Among US Adults With a Major Depressive Episode and Suicidal Ideation or Behavior With Intent.
Voelker J, Cai Q, Kuvadia H, Daly E, Connolly N, Pesa J, Sheehan J, Wilkinson S. Mental Health Care Resource Utilization and Barriers to Receiving Mental Health Services Among US Adults With a Major Depressive Episode and Suicidal Ideation or Behavior With Intent. The Journal Of Clinical Psychiatry 2021, 82 PMID: 34529898, DOI: 10.4088/jcp.20m13842.Peer-Reviewed Original ResearchConceptsMajor depressive episodeMental health servicesHealth care resource utilizationHealth servicesSuicidal ideationDepressive episodeMental health treatmentLogistic regression modelsPrescription medicationsOutpatient careInpatient careHigher oddsExtensive burdenHealth treatmentUnmet needDrug useCohortCareAdult participantsNational surveyIdeationRegression modelsGreatest barrierTreatmentEpisodes
2018
Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD)
Fava M, Freeman MP, Flynn M, Judge H, Hoeppner BB, Cusin C, Ionescu DF, Mathew SJ, Chang LC, Iosifescu DV, Murrough J, Debattista C, Schatzberg AF, Trivedi MH, Jha MK, Sanacora G, Wilkinson ST, Papakostas GI. Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD). Molecular Psychiatry 2018, 25: 1592-1603. PMID: 30283029, PMCID: PMC6447473, DOI: 10.1038/s41380-018-0256-5.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionSingle doseActive placeboSubanesthetic dosesIntravenous ketamineAdult treatment-resistant depressionTransient blood pressure elevationTransient antidepressant effectsBlood pressure elevationPlacebo-controlled studyDose-ranging trialInfusion of ketaminePrimary outcome measureAbility of ketamineCurrent depressive episodeSingle intravenous doseNMDA receptor antagonistTime interaction effectsMeaningful efficacyAntidepressant doseGreater dissociative symptomsAdjunctive therapyAntidepressant effectsEligible subjectsSecondary outcomesLeveraging Neuroplasticity to Enhance Adaptive Learning: The Potential for Synergistic Somatic-Behavioral Treatment Combinations to Improve Clinical Outcomes in Depression
Wilkinson ST, Holtzheimer PE, Gao S, Kirwin DS, Price RB. Leveraging Neuroplasticity to Enhance Adaptive Learning: The Potential for Synergistic Somatic-Behavioral Treatment Combinations to Improve Clinical Outcomes in Depression. Biological Psychiatry 2018, 85: 454-465. PMID: 30528745, PMCID: PMC6380941, DOI: 10.1016/j.biopsych.2018.09.004.Peer-Reviewed Original ResearchConceptsClinical outcomesN-methyl-D-aspartate receptor modulatorsLong-term clinical outcomesLong-term treatment outcomesBehavioral interventionsImpairment of neuroplasticityUnderstanding of pathophysiologyStand-alone treatmentTranscranial brain stimulationNeuroplasticity deficitsSymptom burdenElectroconvulsive therapyReceptor modulatorsTreatment outcomesEnhanced neuroplasticityMood disordersDepressive symptomsBrain stimulationTreatment approachesSymptom reductionNeuroplasticityNeuropsychiatric disordersBehavioral therapyDisease statesTherapeutic developmentAcute and Longer-Term Outcomes Using Ketamine as a Clinical Treatment at the Yale Psychiatric Hospital.
Wilkinson ST, Katz RB, Toprak M, Webler R, Ostroff RB, Sanacora G. Acute and Longer-Term Outcomes Using Ketamine as a Clinical Treatment at the Yale Psychiatric Hospital. The Journal Of Clinical Psychiatry 2018, 79 PMID: 30063304, PMCID: PMC6296748, DOI: 10.4088/jcp.17m11731.Peer-Reviewed Original ResearchConceptsMood disordersClinical treatmentTreatment-resistant mood disordersResearch protocolLong-term adverse effectsRapid-acting antidepressantsLong-term safetyEmergence of symptomsRemission rateKetamine infusionFourth infusionLabel therapyTerm outcomesAuthors' institutionPsychiatric hospitalTotal infusionPatientsCognitive declineKetamineTotal treatmentInfusionAdverse effectsClinical samplesLong-term basisTreatmentIdentifying Recipients of Electroconvulsive Therapy: Data From Privately Insured Americans
Wilkinson ST, Agbese E, Leslie DL, Rosenheck RA. Identifying Recipients of Electroconvulsive Therapy: Data From Privately Insured Americans. Psychiatric Services 2018, 69: 542-548. PMID: 29385954, PMCID: PMC6248332, DOI: 10.1176/appi.ps.201700364.Peer-Reviewed Original ResearchConceptsElectroconvulsive therapyMood disordersClinical characteristicsECT useUse of ECTCharacteristics of patientsProportion of patientsComorbid psychiatric disordersMajor depressive disorderNumber of prescriptionsSubstance use disordersOutpatient psychotherapy visitsECT patientsECT utilization rateMarketScan databasePsychotherapy visitsPsychotropic medicationsDepressive disorderPsychiatric disordersService useUse disordersPatientsECT utilizationBipolar disorderCommercial insurance
2017
The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis
Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, Sos P, Wang G, Zarate CA, Sanacora G. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. American Journal Of Psychiatry 2017, 175: 150-158. PMID: 28969441, PMCID: PMC5794524, DOI: 10.1176/appi.ajp.2017.17040472.Peer-Reviewed Original ResearchConceptsIndividual participant dataLong-term safetySuicidal ideationKetamine effectsSingle doseParticipant dataSuicide itemOutcome measuresSystematic reviewIndividual Participant Data Meta-AnalysisLimited treatment optionsPrimary outcome measureSelf-reported outcome measuresData Meta-AnalysisIntravenous ketaminePublic health crisisKetamine administrationTreatment optionsQIDS-SRDepressed patientsDepressive symptomsIntervention studiesKetamineMeta-AnalysisSuicidal thoughtsConsiderations on the Off-Label Use of Ketamine as a Treatment for Mood Disorders
Wilkinson ST, Sanacora G. Considerations on the Off-Label Use of Ketamine as a Treatment for Mood Disorders. JAMA 2017, 318: 793-794. PMID: 28806440, PMCID: PMC6248331, DOI: 10.1001/jama.2017.10697.Commentaries, Editorials and LettersA Survey of the Clinical, Off-Label Use of Ketamine as a Treatment for Psychiatric Disorders
Wilkinson ST, Toprak M, Turner MS, Levine SP, Katz RB, Sanacora G. A Survey of the Clinical, Off-Label Use of Ketamine as a Treatment for Psychiatric Disorders. American Journal Of Psychiatry 2017, 174: 695-696. PMID: 28669202, PMCID: PMC5549850, DOI: 10.1176/appi.ajp.2017.17020239.Peer-Reviewed Original Research