2023
Single-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 eventsLong-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 ratingsProphylactic Efficacy of Riluzole against Anxiety- and Depressive-Like Behaviors in Two Rodent Stress Models
Bansal Y, Fee C, Misquitta K, Codeluppi S, Sibille E, Berman R, Coric V, Sanacora G, Banasr M. Prophylactic Efficacy of Riluzole against Anxiety- and Depressive-Like Behaviors in Two Rodent Stress Models. Complex Psychiatry 2023, 9: 57-69. PMID: 37101541, PMCID: PMC10123365, DOI: 10.1159/000529534.Peer-Reviewed Original ResearchUnpredictable chronic mild stressAnhedonia-like behaviorHelplessness-like behaviorStress-related disordersFirst-line antidepressant drugsNovelty-induced hypophagia testDepressive-like behaviorChronic mild stressHigh relapse rateSucrose consumption testNovelty-suppressed feedingRodent stress modelsMajor depressive disorderAnxiety-like behaviorOpen field testBehavioral emotionalityRiluzole efficacyRiluzole treatmentHypophagia testRelapse rateProphylactic medicationStress-related illnessesProphylactic efficacyProphylactic treatmentSpecific symptom dimensions
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 correlationEfficacy 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
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 disorderKetamine
2011
The 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
Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole
Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL, Sanacora G. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Molecular Psychiatry 2008, 15: 501-511. PMID: 18825147, PMCID: PMC3347761, DOI: 10.1038/mp.2008.106.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAnimalsAvoidance LearningBehavioral SymptomsDepressionDisease Models, AnimalFood PreferencesGene Expression RegulationGlial Fibrillary Acidic ProteinGlutamic AcidIsotopesMagnetic Resonance SpectroscopyMaleNeurogliaNeuroprotective AgentsPrefrontal CortexRadionuclide ImagingRatsRats, Sprague-DawleyRiluzoleRNA, MessengerStatistics, NonparametricStress, PsychologicalSucroseSweetening AgentsConceptsChronic unpredictable stressPrefrontal cortexGlial dysfunctionGlial functionBehavioral deficitsDrug riluzoleOpen-label clinical trialMRNA expressionAmino acid neurotransmissionAntidepressant drug developmentDepressive-like behaviorPathophysiology of depressionEffects of riluzoleGlial cell metabolismMajor depressive disorderRat prefrontal cortexGFAP mRNA expressionProtein mRNA expressionNeurotransmitter system abnormalitiesGlia pathologyGlial pathologyRiluzole treatmentAntidepressant actionChronic treatmentGlutamate releaseTargeting 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