2024
Effect of Esketamine Nasal Spray on Cognition in Patients With Treatment-Resistant Depression: Results From Four Phase 3 Studies
Morrison R, Singh J, Daly E, Fedgchin M, Ochs-Ross R, Karcher K, Lane R, Cooper K, Sanacora G, Maruff P, Drevets W. Effect of Esketamine Nasal Spray on Cognition in Patients With Treatment-Resistant Depression: Results From Four Phase 3 Studies. The International Journal Of Neuropsychopharmacology 2024, 27: pyae046. PMID: 39514643, PMCID: PMC11561565, DOI: 10.1093/ijnp/pyae046.Peer-Reviewed Original ResearchEsketamine nasal sprayTreatment-resistant depressionLong-term maintenance treatmentMADRS scoreOral antidepressantHopkins Verbal Learning Test-RevisedMaintenance treatmentCognitive test batteryEffects of esketamineGroup mean performanceFollow-up assessmentMild to moderate impairmentDepression severityTest-RevisedCogState batteryCognitive performancePsychomotor functionTest batteryCognitive testsCognitionEsketamineNasal sprayEffect sizeDepressionEffects of short-termKetamine 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
Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions
McIntyre R, Alsuwaidan M, Baune B, Berk M, Demyttenaere K, Goldberg J, Gorwood P, Ho R, Kasper S, Kennedy S, Ly-Uson J, Mansur R, McAllister-Williams R, Murrough J, Nemeroff C, Nierenberg A, Rosenblat J, Sanacora G, Schatzberg A, Shelton R, Stahl S, Trivedi M, Vieta E, Vinberg M, Williams N, Young A, Maj M. Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry 2023, 22: 394-412. PMID: 37713549, PMCID: PMC10503923, DOI: 10.1002/wps.21120.Peer-Reviewed Original ResearchTreatment-resistant depressionTranscranial magnetic stimulationEuropean Medicines AgencyIntravenous ketamineManagement of TRDRepetitive transcranial magnetic stimulationOlanzapine-fluoxetine combinationSecond-generation antipsychoticsSignificant symptomatic reliefManual-based psychotherapiesSerious public health implicationsTheta-burst transcranial magnetic stimulationQuality of carePublic health implicationsIntranasal esketaminePartial respondersAdjunctive treatmentElectroconvulsive therapySymptomatic reliefConventional antidepressantsMedication switchingAntidepressant trialsRisk factorsInvestigational interventionMagnetic stimulationLong-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 ratingsArketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study
Leal G, Souza-Marques B, Mello R, Bandeira I, Caliman-Fontes A, Carneiro B, Faria-Guimarães D, Guerreiro-Costa L, Jesus-Nunes A, Silva S, Lins-Silva D, Fontes M, Alves-Pereira R, Cordeiro V, Rugieri-Pacheco S, Santos-Lima C, Correia-Melo F, Vieira F, Sanacora G, Lacerda A, Quarantini L. Arketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study. Journal Of Affective Disorders 2023, 330: 7-15. PMID: 36871913, DOI: 10.1016/j.jad.2023.02.151.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionAntidepressant effectsPlacebo-controlled pilot studyPilot studyMain efficacy analysisAdjunctive therapyAdverse eventsOne-week intervalEfficacy analysisPreclinical dataFlexible dosesClinical trialsPilot trialHuman trialsSide effectsRacemic ketaminePlaceboFirst weekKetamineTrialsTreatment effectsSignificant differencesDepressionEffects modelParallel design
2022
Effect of Concomitant Benzodiazepines on the Antidepressant Effects of Ketamine: Findings From the RAPID Intravenous Ketamine Study.
Feeney A, Hoeppner B, Freeman M, Flynn M, Iosifescu D, Trivedi M, Sanacora G, Mathew S, DeBattista C, Ionescu D, Cusin C, Papakostas G, Jha M, Fava M. Effect of Concomitant Benzodiazepines on the Antidepressant Effects of Ketamine: Findings From the RAPID Intravenous Ketamine Study. The Journal Of Clinical Psychiatry 2022, 84 PMID: 36383742, DOI: 10.4088/jcp.22m14491.Peer-Reviewed Original ResearchConceptsMajor depressive disorderDifferential treatment responsePrimary outcome measureBenzodiazepine useOral benzodiazepinesTreatment responseDay 1Antidepressant effectsHigh dosesClinical Global Impressions-SeverityHamilton Depression Rating ScaleStudy's primary outcome measureIllness Scale scoresTreatment-resistant depressionRandomized clinical trialsDepression Rating ScaleBenzodiazepine dosageIntravenous ketamineConcomitant benzodiazepinesSingle infusionClinical trialsDepressive disorderKetamine studiesOutcome measuresBenzodiazepine effectsEfficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial
Dwyer J, Landeros-Weisenberger A, Johnson J, Londono Tobon A, Flores J, Nasir M, Couloures K, Sanacora G, Bloch M. Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial. FOCUS The Journal Of Lifelong Learning In Psychiatry 2022, 20: 241-251. PMID: 37153136, PMCID: PMC10153503, DOI: 10.1176/appi.focus.22020004.Peer-Reviewed Original ResearchTreatment-resistant depressionDepression Rating ScaleIntravenous ketamineClinical trialsAdolescent treatment-resistant depressionAdult treatment-resistant depressionPlacebo-controlled clinical trialSignificant short-term efficacySerious adverse eventsPrimary outcome measureSingle intravenous infusionChildren's Depression Rating ScaleCrossover clinical trialShort-term efficacyMajor depressive disorderSingle ketamine infusionSymptoms 24 hoursLater time pointsKetamine’s safetyAdverse eventsAntidepressant medicationKetamine infusionPediatric populationSignificant morbidityIntravenous infusion
2019
POST HOC ANALYSES OF ESKETAMINE NASAL SPRAY PLUS AN ORAL ANTIDEPRESSANT IN ELDERLY PATIENTS WITH TREATMENT-RESISTANT DEPRESSION
Ochs-Ross R, Daly E, Zhang Y, Lane R, Lim P, Foster K, Hough D, Manji H, Drevets W, Sanacora G, Adler C, McShane R, Gaillard R, Singh J. POST HOC ANALYSES OF ESKETAMINE NASAL SPRAY PLUS AN ORAL ANTIDEPRESSANT IN ELDERLY PATIENTS WITH TREATMENT-RESISTANT DEPRESSION. American Journal Of Geriatric Psychiatry 2019, 27: s140-s141. DOI: 10.1016/j.jagp.2019.01.094.Peer-Reviewed Original ResearchTreatment-resistant depressionMADRS total scoreOpen-label safety studyEsketamine nasal sprayLabel Safety StudyLS mean differenceNew oral antidepressantDuration of treatmentOnset of depressionInterim analysisOral antidepressantsYears of ageNasal sprayPrimary analysisElderly patientsTotal scoreMean changeLarge phase 3 studiesDay 25Mean differenceStage 2Safety studiesPrimary efficacy endpointPhase 3 studyUnexpected safety concernsEFFICACY AND SAFETY OF ESKETAMINE NASAL SPRAY PLUS AN ORAL ANTIDEPRESSANT IN ELDERLY PATIENTS WITH TREATMENT-RESISTANT DEPRESSION
Ochs-Ross R, Daly E, Zhang Y, Lane R, Lim P, Foster K, Hough D, Manji H, Drevets W, Sanacora G, Adler C, McShane R, Gaillard R, Singh J. EFFICACY AND SAFETY OF ESKETAMINE NASAL SPRAY PLUS AN ORAL ANTIDEPRESSANT IN ELDERLY PATIENTS WITH TREATMENT-RESISTANT DEPRESSION. American Journal Of Geriatric Psychiatry 2019, 27: s139-s140. DOI: 10.1016/j.jagp.2019.01.093.Peer-Reviewed Original ResearchEsketamine nasal sprayTreatment-emergent adverse eventsTreatment-resistant depressionPlacebo nasal sprayCommon treatment-emergent adverse eventsTreatment of TRDMADRS total scoreElderly patientsNasal sprayOral antidepressantsTotal scoreDay 28Montgomery-Åsberg Depression Rating Scale (MADRS) total scoreBaseline MADRS total scoreDouble-blind treatment phasePre-specified subgroup analysisFirst large clinical trialJanssen ResearchMean patient ageSafety of esketamineLarge clinical trialsNew safety concernsActive-controlled studyScale total scoreYears of ageEfficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression
Ochs-Ross R, Daly E, Zhang Y, Lane R, Lim P, Foster K, Hough D, Manji H, Drevets W, Sanacora G, Adler C, McShane R, Gaillard R, Singh J. Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression. European Neuropsychopharmacology 2019, 29: s355-s356. DOI: 10.1016/j.euroneuro.2018.11.548.Peer-Reviewed Original ResearchEsketamine nasal sprayTreatment-resistant depressionOral antidepressantsElderly patientsNasal sprayAntidepressantsPatientsLong-term safety of esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: SUSTAIN-2 phase 3 study
Wajs E, Leah A, Morrison R, Daly E, Lane R, Lim P, Holder R, Sanacora G, Young A, Kasper S, Sulaiman A, Li C, Paik J, Manji H, Hough D, Drevets W, Singh J. Long-term safety of esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: SUSTAIN-2 phase 3 study. European Neuropsychopharmacology 2019, 29: s44-s45. DOI: 10.1016/j.euroneuro.2018.11.1016.Peer-Reviewed Original ResearchEsketamine nasal sprayPhase 3 studyTreatment-resistant depressionLong-term safetyOral antidepressantsNasal sprayAntidepressantsPatients
2018
S114. Efficacy and Safety of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression
Ochs-Ross R, Daly E, Zhang Y, Lane R, Lim P, Foster K, Hough D, Manji H, Drevets W, Sanacora G, Adler C, McShane R, Gaillard R, Singh J. S114. Efficacy and Safety of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression. Biological Psychiatry 2018, 83: s391. DOI: 10.1016/j.biopsych.2018.02.1005.Peer-Reviewed Original ResearchTreatment-resistant depressionIntranasal esketamineOral antidepressantsElderly patientsEsketamineAntidepressantsPatients
2014
P.2.b.017 Onset of efficacy of ketamine in treatment-resistant depression: a double-blind, randomised, placebo-controlled, dose frequency study
Singh J, Fedgchin M, Daly E, De Boer P, Cooper K, Lim P, Pinter C, Murrough J, Sanacora G, Shelton R, Kurian B, Winokur A, Fava M, Manji H, Drevets W, Van Nueten L. P.2.b.017 Onset of efficacy of ketamine in treatment-resistant depression: a double-blind, randomised, placebo-controlled, dose frequency study. European Neuropsychopharmacology 2014, 24: s387-s388. DOI: 10.1016/s0924-977x(14)70618-2.Peer-Reviewed Original Research