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 improvementDepression - Advanced Treatments for Treatment-Resistant Depression.
Cristancho M, Fava M, Ingelfinger J, Nikayin S, Sanacora G. Depression - Advanced Treatments for Treatment-Resistant Depression. New England Journal Of Medicine 2024, 390: e44. PMID: 38810184, DOI: 10.1056/nejmp2310181.Peer-Reviewed Original ResearchDepression - Treatment Options and Managing Depression in Primary Care.
Anderson E, Crawford C, Fava M, Ingelfinger J, Sanacora G, Scott-Vernaglia S, Teel J. Depression - Treatment Options and Managing Depression in Primary Care. New England Journal Of Medicine 2024, 390: e44. PMID: 38749042, DOI: 10.1056/nejmp2310180.Peer-Reviewed Original ResearchDepression - Understanding, Identifying, and Diagnosing.
Anderson E, Crawford C, Fava M, Ingelfinger J, Nikayin S, Sanacora G, Scott-Vernaglia S, Teel J. Depression - Understanding, Identifying, and Diagnosing. New England Journal Of Medicine 2024, 390: e41. PMID: 38692291, DOI: 10.1056/nejmp2310179.Peer-Reviewed Original Research
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 indicationsSingle-Dose Psilocybin Treatment for Major Depressive Disorder
Raison C, Sanacora G, Woolley J, Heinzerling K, Dunlop B, Brown R, Kakar R, Hassman M, Trivedi R, Robison R, Gukasyan N, Nayak S, Hu X, O’Donnell K, Kelmendi B, Sloshower J, Penn A, Bradley E, Kelly D, Mletzko T, Nicholas C, Hutson P, Tarpley G, Utzinger M, Lenoch K, Warchol K, Gapasin T, Davis M, Nelson-Douthit C, Wilson S, Brown C, Linton W, Johnson M, Ross S, Griffiths R. Single-Dose Psilocybin Treatment for Major Depressive Disorder. JAMA 2023, 330: 843-853. PMID: 37651119, PMCID: PMC10472268, DOI: 10.1001/jama.2023.14530.Peer-Reviewed Original ResearchConceptsMajor depressive disorderSheehan Disability Scale scoresAdverse eventsDisability scale scorePsilocybin treatmentDay 43Scale scoreSecondary outcomesSingle doseDepressive disorderExclusion criteriaPsychological supportMontgomery-Asberg Depression Rating Scale scoreSerious treatment-emergent adverse eventsDay 8Key secondary outcome measuresTreatment-emergent adverse eventsDepression Rating Scale scoresActive substance use disorderFifth Edition diagnosisIdentical-appearing capsulesOverall adverse eventsPhase 2 trialSerious adverse eventsSevere adverse eventsThe Intricate Interaction Between Expectations and Therapeutic Outcomes of Psychedelic Agents
Colloca L, Nikayin S, Sanacora G. The Intricate Interaction Between Expectations and Therapeutic Outcomes of Psychedelic Agents. JAMA Psychiatry 2023, 80: 867-868. PMID: 37405764, PMCID: PMC10868530, DOI: 10.1001/jamapsychiatry.2023.1412.Peer-Reviewed Original ResearchUsing latent profile analyses to classify subjects with anhedonia based on reward-related measures obtained in the FAST-MAS study
Darrow S, Pizzagalli D, Smoski M, Mathew S, Nurnberger J, Lisanby S, Iosifescu D, Murrough J, Yang H, Weiner R, Sanacora G, Keefe R, Song A, Goodman W, Whitton A, Potter W, Krystal A. Using latent profile analyses to classify subjects with anhedonia based on reward-related measures obtained in the FAST-MAS study. Journal Of Affective Disorders 2023, 339: 584-592. PMID: 37467805, DOI: 10.1016/j.jad.2023.07.081.Peer-Reviewed Original ResearchConceptsSelf-report measuresKetamine 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 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 effectsDifferences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder
Holmes S, Asch R, Davis M, DellaGioia N, Pashankar N, Gallezot J, Nabulsi N, Matuskey D, Sanacora G, Carson R, Blumberg H, Esterlis I. Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder. Biological Psychiatry 2022, 93: 1099-1107. PMID: 36764853, PMCID: PMC10164841, DOI: 10.1016/j.biopsych.2022.10.018.Peer-Reviewed Original ResearchConceptsMajor depressive disorderMetabotropic glutamate receptor 5Glutamate receptor 5MGluR5 availabilityBipolar disorderPositron emission tomographyHC groupDepressive disorderReceptor 5Emission tomographyHealthy control individualsPossible treatment targetsGlutamate transmissionBD depressionTreatment strategiesBD groupMGluR5Depressive symptomsNovel treatmentsCognitive alterationsTreatment targetsSynaptic plasticityControl individualsAccurate diagnosisSignificant negative correlation
2021
Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions
Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, Aslan M, Quaden R, Harrington KM, Nuñez YZ, Overstreet C, Radhakrishnan K, Sanacora G, McIntosh AM, Shi J, Shringarpure SS, Concato J, Polimanti R, Gelernter J. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience 2021, 24: 954-963. PMID: 34045744, PMCID: PMC8404304, DOI: 10.1038/s41593-021-00860-2.Peer-Reviewed Original ResearchConceptsTranscriptome-wide association studyMillion Veteran ProgramTranscriptome-wide association study (TWAS) analysisGenomic risk lociComplex psychiatric traitsGenetic architectureRisk lociGene expressionAssociation studiesLikely pathogenicityPsychiatric traitsVeteran ProgramNew therapeutic directionEuropean ancestryNew insightsAncestryUK BiobankAfrican ancestrySubstantial replicationExpressionLarge independent cohortsGWASTherapeutic directionsGenesLoci
2012
Rapid Antidepressant Effect of Ketamine in the Electroconvulsive Therapy Setting
Abdallah CG, Fasula M, Kelmendi B, Sanacora G, Ostroff R. Rapid Antidepressant Effect of Ketamine in the Electroconvulsive Therapy Setting. Journal Of Ect 2012, 28: 157-161. PMID: 22847373, PMCID: PMC3426617, DOI: 10.1097/yct.0b013e31824f8296.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnesthesiaAnesthetics, DissociativeAntidepressive AgentsBipolar DisorderCombined Modality TherapyDepressionDepressive Disorder, MajorElectroconvulsive TherapyElectroencephalographyFemaleHumansHypnotics and SedativesKetamineMaleMiddle AgedPsychiatric Status Rating ScalesSeizuresThiopentalTreatment OutcomeYoung AdultConceptsHamilton Depression Rating ScaleAntidepressant effectsElectroconvulsive therapyECT sessionsDepressive episodeN-methyl-D-aspartate receptor antagonist ketamineN-methyl-D-aspartate antagonistsCoadministration of ketamineFirst ECT sessionRapid antidepressant effectsSevere depressive episodeSignificant antidepressant effectMajor depressive episodeDepression Rating ScaleMajor depressive disorderSixth ECT sessionSignificant group effectImmediate antidepressant effectECT treatmentAntidepressant propertiesHDRS scoresDepressive disorderLow doseBipolar disorderKetamineBrain-Derived Neurotrophic Factor Val66Met Polymorphism and Antidepressant Efficacy of Ketamine in Depressed Patients
Laje G, Lally N, Mathews D, Brutsche N, Chemerinski A, Akula N, Kelmendi B, Simen A, McMahon FJ, Sanacora G, Zarate C. Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Antidepressant Efficacy of Ketamine in Depressed Patients. Biological Psychiatry 2012, 72: e27-e28. PMID: 22771240, PMCID: PMC3786174, DOI: 10.1016/j.biopsych.2012.05.031.Peer-Reviewed Original ResearchCortical GABA Levels in Primary Insomnia
Morgan PT, Pace-Schott EF, Mason GF, Forselius E, Fasula M, Valentine GW, Sanacora G. Cortical GABA Levels in Primary Insomnia. Sleep 2012, 35: 807-814. PMID: 22654200, PMCID: PMC3353043, DOI: 10.5665/sleep.1880.Peer-Reviewed Original ResearchConceptsGABA levelsSleep complaintsPrimary insomniaSleep onsetCortical GABA levelsGABA/creatine ratiosOccipital GABA levelsPolysomnographic sleep measuresBrain GABA levelsBody mass indexMain outcome measuresUniversity research clinicPrimary insomnia groupAllostatic responseProton magnetic resonance spectroscopyMaintenance of sleepGABA contentUse of cigarettesUse of caffeineMass indexOutpatient studyCreatine ratioOutcome measuresResearch clinicTwo-group comparison study
2011
The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission
Popoli M, Yan Z, McEwen BS, Sanacora G. The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nature Reviews Neuroscience 2011, 13: 22-37. PMID: 22127301, PMCID: PMC3645314, DOI: 10.1038/nrn3138.Peer-Reviewed Original ResearchConceptsGlutamate releaseGlutamate transmissionAcute stressCognitive functionPrefrontal cortexPrefrontal cortex-dependent cognitive functionsGlutamatergic synaptic transmissionLimbic brain areasGlutamatergic neurotransmitter systemChronic stress exposureUnmet therapeutic needMonoaminergic mechanismsNeurochemical mediatorsCertain cognitive functionsLimbic regionsPrimary neurotransmitterNMDA receptorsGlutamate receptorsNeurotransmitter systemsPharmacological interventionsSynaptic transmissionGlutamate synapseMaladaptive changesBrain areasBrain tissueThe antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [1H]-MRS
Valentine GW, Mason GF, Gomez R, Fasula M, Watzl J, Pittman B, Krystal JH, Sanacora G. The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [1H]-MRS. Psychiatry Research 2011, 191: 122-127. PMID: 21232924, PMCID: PMC3061550, DOI: 10.1016/j.pscychresns.2010.10.009.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntidepressive AgentsBlood PressureDepressive Disorder, MajorDissociative DisordersFemaleGamma-Aminobutyric AcidGlutamic AcidHeart RateHumansKetamineMagnetic Resonance SpectroscopyMaleMiddle AgedOccipital LobeProtonsPsychiatric Status Rating ScalesPsychometricsRetrospective StudiesSingle-Blind MethodStatistics as TopicTime FactorsYoung AdultConceptsMajor depressive disorderAntidepressant effectsAntidepressant actionNeurotransmitter contentNMDA receptor antagonist ketamineProton magnetic resonance spectroscopy methodConventional antidepressant treatmentKetamine's antidepressant actionSingle intravenous doseSingle-blind conditionsAntidepressant treatmentChronic treatmentKetamine infusionIntravenous dosePharmacodynamic basisDepressive disorderAcute actionsMRS scansOccipital cortexDepressive symptomsDepression scoresRating ScaleBaseline measuresInfusionKetamine
2008
Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders
Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nature Reviews Drug Discovery 2008, 7: 426-437. PMID: 18425072, PMCID: PMC2715836, DOI: 10.1038/nrd2462.Peer-Reviewed Original ResearchConceptsGlutamatergic systemMood disordersAntidepressant effectsNMDA antagonistsDouble-blind placebo-controlled crossover studyTreatment-resistant major depressive disorderPlacebo-controlled crossover studyGlutamate release inhibitorSignificant antidepressant effectNMDA receptor expressionRecurrent mental illnessSingle intravenous doseMajor depressive disorderPotential novel therapeuticsGlutamatergic abnormalitiesCrossover studyGlutamate releaseIntravenous doseMood stabilizersDepressive disorderReceptor expressionReceptor modulatorsEvidence of alterationsCerebrospinal fluidAMPA potentiators