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 ResearchEfficacy 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 rateRemissionKetamine 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 ResearchMeSH KeywordsAntidepressive AgentsDepressionDepressive Disorder, MajorDepressive Disorder, Treatment-ResistantDouble-Blind MethodHumansNasal SpraysTreatment OutcomeConceptsTreatment-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 ResearchMeSH KeywordsAntidepressive AgentsCognitive Behavioral TherapyDepressionDepressive Disorder, Treatment-ResistantHumansPsychotherapyConceptsTreatment-resistant depressionRole of psychotherapySomatic therapiesLong-term outcomesPositive therapeutic benefitsPsychotherapy modalitiesRandomized trialsMood disordersTherapeutic benefitNeural plasticityTherapyMore trialsForms of psychotherapyTrialsDepressionLess evidenceModalitiesPsychotherapy approachesPsychotherapyPotential combinations
2022
International 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 ResearchMeSH KeywordsAdministration, IntravenousAntidepressive AgentsBipolar DisorderDepressionHumansKetamineTreatment OutcomeConceptsMontgomery-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 severity
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 ResearchMeSH KeywordsAntidepressive AgentsBehavior TherapyCombined Modality TherapyDepressionElectroconvulsive TherapyHumansNeuronal PlasticityTranscranial Magnetic StimulationConceptsClinical 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 basisTreatment
2017
A 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 ResearchCognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression
Wilkinson ST, Wright D, Fasula MK, Fenton L, Griepp M, Ostroff RB, Sanacora G. Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression. Psychotherapy And Psychosomatics 2017, 86: 162-167. PMID: 28490030, PMCID: PMC5516265, DOI: 10.1159/000457960.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAdultAntidepressive AgentsCognitionCognitive Behavioral TherapyCombined Modality TherapyDepressive Disorder, MajorDepressive Disorder, Treatment-ResistantFemaleHumansKaplan-Meier EstimateKetamineMaleMiddle AgedPsychiatric Status Rating ScalesRecurrenceRemission InductionTreatment OutcomeYoung AdultConceptsTreatment-resistant depressionCognitive behavioral therapyAntidepressant effectsKetamine's antidepressant effectsKetamine exposureIntravenous ketamineKetamine infusion therapyWeeks of protocolOpen-label trialLong-term treatmentStandardized clinical protocolCognitive behavior therapyKetamine nonrespondersKetamine respondersRelapse rateMedian timeInfusion therapyClinical protocolsKetamineNeurobiological changesRemissionBehavioral therapyTherapyWeeksBehavior therapy