2022
Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial
Abdallah CG, Roache JD, Gueorguieva R, Averill LA, Young-McCaughan S, Shiroma PR, Purohit P, Brundige A, Murff W, Ahn KH, Sherif MA, Baltutis EJ, Ranganathan M, D’Souza D, Martini B, Southwick SM, Petrakis IL, Burson RR, Guthmiller KB, López-Roca AL, Lautenschlager KA, McCallin JP, Hoch MB, Timchenko A, Souza SE, Bryant CE, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH. Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial. Neuropsychopharmacology 2022, 47: 1574-1581. PMID: 35046508, PMCID: PMC8767037, DOI: 10.1038/s41386-022-01266-9.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderClinical trialsOutcome measuresMontgomery-Åsberg Depression Rating ScaleSelf-report PTSD ChecklistÅsberg Depression Rating ScaleStress disorderPTSD symptomsAntidepressant-resistant symptomsPrevious antidepressant treatmentClinician-Administered PTSD ScaleMulti-center clinical trialRapid antidepressant effectsSecondary outcome measuresPrimary outcome measureSignificant dose-related effectsRole of ketamineDepression Rating ScaleDose-related effectsEffects of ketamineDSM-5Intravenous placeboDose ketamineTreatment discontinuationActive duty military
2020
Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin
Abdallah CG, Averill LA, Gueorguieva R, Goktas S, Purohit P, Ranganathan M, Sherif M, Ahn KH, D’Souza D, Formica R, Southwick SM, Duman RS, Sanacora G, Krystal JH. Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin. Neuropsychopharmacology 2020, 45: 990-997. PMID: 32092760, PMCID: PMC7162891, DOI: 10.1038/s41386-020-0644-9.Peer-Reviewed Original ResearchConceptsAntidepressant effectsKetamine administrationRapamycin pretreatmentMontgomery-Åsberg Depression Rating ScaleDouble-blind cross-over designBenefits of ketamineRobust antidepressant effectsKetamine's antidepressant effectsMajor depressive episodeDepression Rating ScaleCross-over designKetamine exertsOral rapamycinRemission rateDepressive episodePlacebo 2Ketamine 0.5Local blockadeDepressed patientsIntravenous administrationTreatment daysDepression relapseDepression severityKetamineRating Scale
2017
Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression
Su TP, Chen MH, Li CT, Lin WC, Hong CJ, Gueorguieva R, Tu PC, Bai YM, Cheng CM, Krystal JH. Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. Neuropsychopharmacology 2017, 42: 2482-2492. PMID: 28492279, PMCID: PMC5686503, DOI: 10.1038/npp.2017.94.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsAsian PeopleBlood PressureBrain-Derived Neurotrophic FactorDepressive Disorder, MajorDepressive Disorder, Treatment-ResistantDose-Response Relationship, DrugDouble-Blind MethodFemaleHeart RateHumansKetamineMaleMiddle AgedPolymorphism, GeneticPsychiatric Status Rating ScalesTaiwanTreatment OutcomeConceptsTreatment-resistant depressionHamilton Depression Rating ScaleAntidepressant effectsKetamine effectsBDNF genotypeBrain-derived neurotrophic factor (BDNF) genotypeChinese populationDose-related efficacyPlacebo-controlled trialSignificant dose-related effectsDepression Rating ScaleNeurotrophic factor genotypeDose-related effectsSingle ketamine infusionMost patientsKetamine infusionTaiwanese patientsAdjunctive ketamineResponder analysisBDNF geneS-ketamineKetamine levelsPatientsMet alleleRating ScaleReevaluating the Efficacy and Predictability of Antidepressant Treatments: A Symptom Clustering Approach
Chekroud AM, Gueorguieva R, Krumholz HM, Trivedi MH, Krystal JH, McCarthy G. Reevaluating the Efficacy and Predictability of Antidepressant Treatments: A Symptom Clustering Approach. JAMA Psychiatry 2017, 74: 370-378. PMID: 28241180, PMCID: PMC5863470, DOI: 10.1001/jamapsychiatry.2017.0025.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAffectAgedAntidepressive AgentsBupropionCitalopramCluster AnalysisDepressive Disorder, MajorDose-Response Relationship, DrugDrug Therapy, CombinationDuloxetine HydrochlorideFemaleHumansMaleMianserinMiddle AgedMirtazapineRandomized Controlled Trials as TopicSleepSyndromeTreatment OutcomeVenlafaxine HydrochlorideYoung AdultConceptsCore emotional symptomsDepressive severitySymptom clustersHamilton Depression Rating ScaleDepression Outcomes trialDifferent antidepressant medicationsHAM-D scaleHigh-dose duloxetinePhase 3 trialEmotional symptomsPatient-reported dataDepression Rating ScaleSequenced Treatment AlternativesGroup of symptomsCluster of symptomsDepressive symptom checklistMixed-effects regression analysisDepressive Symptomatology ScaleAntidepressant therapyAntidepressant treatmentAntidepressant medicationOutcome trialsCombining MedicationsAtypical symptomsAdditional placebo
2016
Reduced global functional connectivity of the medial prefrontal cortex in major depressive disorder
Murrough JW, Abdallah CG, Anticevic A, Collins KA, Geha P, Averill LA, Schwartz J, DeWilde KE, Averill C, Jia-Wei Yang G, Wong E, Tang CY, Krystal JH, Iosifescu DV, Charney DS. Reduced global functional connectivity of the medial prefrontal cortex in major depressive disorder. Human Brain Mapping 2016, 37: 3214-3223. PMID: 27144347, PMCID: PMC4980239, DOI: 10.1002/hbm.23235.Peer-Reviewed Original ResearchConceptsGlobal brain connectivityMedial prefrontal cortexPrefrontal cortexRight subgenual anterior cingulate cortexVentromedial prefrontal cortexCingulate cortexMontgomery-Åsberg Depression Rating ScaleSymptom severityBrain connectivitySubgenual anterior cingulate cortexDepression Rating ScaleMedication-free patientsMajor depressive disorderKey pathological featureDepressive symptom severitySubgenual cingulate cortexHum Brain MappAnterior cingulate cortexHigher symptom severityFunctional connectivity analysisFunctional magnetic resonancePathological featuresHealthy groupAltered connectivityDepressive disorder
2011
Adjunctive Risperidone Treatment for Antidepressant-Resistant Symptoms of Chronic Military Service–Related PTSD: A Randomized Trial
Krystal JH, Rosenheck RA, Cramer JA, Vessicchio JC, Jones KM, Vertrees JE, Horney RA, Huang GD, Stock C, Group F. Adjunctive Risperidone Treatment for Antidepressant-Resistant Symptoms of Chronic Military Service–Related PTSD: A Randomized Trial. JAMA 2011, 306: 493-502. PMID: 21813427, DOI: 10.1001/jama.2011.1080.Peer-Reviewed Original ResearchConceptsMilitary-related posttraumatic stress disorderMontgomery-Asberg Depression Rating ScalePosttraumatic stress disorderClinical Global Impression ScaleClinician-Administered PTSD ScaleHamilton Anxiety ScalePlacebo-controlled multicenter trialCAPS scoresSelf-reported weight gainSecond-generation antipsychotic risperidoneAdjunctive risperidone treatmentAntidepressant-resistant symptomsPrimary outcome measureChronic military-related posttraumatic stress disorderGlobal Impression ScaleOutpatient medical centerDepression Rating ScaleSymptoms of depressionQuality of lifePlacebo groupRisperidone groupVeterans RANDAdverse eventsOngoing symptomsMulticenter trial
2006
Preliminary Evidence of Riluzole Efficacy in Antidepressant-Treated Patients with Residual Depressive Symptoms
Sanacora G, Kendell SF, Levin Y, Simen AA, Fenton LR, Coric V, Krystal JH. Preliminary Evidence of Riluzole Efficacy in Antidepressant-Treated Patients with Residual Depressive Symptoms. Biological Psychiatry 2006, 61: 822-825. PMID: 17141740, PMCID: PMC2754299, DOI: 10.1016/j.biopsych.2006.08.037.Peer-Reviewed Original ResearchConceptsHamilton Depression Rating ScaleHamilton Anxiety Rating ScaleTreatment-resistant depressionMajor depressive disorderHARS scoresRating ScaleExcessive glutamatergic neurotransmissionEffects of riluzoleDepression Rating ScaleResidual depressive symptomsAnxiety Rating ScaleRiluzole efficacyMedication regimenAugmentation therapyContinuation phaseAntidepressant activityGlutamate neurotransmissionGlutamatergic neurotransmissionDepressive disorderAnxiolytic effectsDepressive symptomsRiluzolePatientsFirst weekLinear mixed models
1996
Clinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression
Miller HL, Delgado PL, Salomon RM, Berman R, Krystal JH, Heninger GR, Charney DS. Clinical and Biochemical Effects of Catecholamine Depletion on Antidepressant-Induced Remission of Depression. JAMA Psychiatry 1996, 53: 117-128. PMID: 8629887, DOI: 10.1001/archpsyc.1996.01830020031005.Peer-Reviewed Original ResearchConceptsNorepinephrine reuptake inhibitorsReuptake inhibitorsCatecholamine depletionAlpha-methylparatyrosineTreatment groupsHamilton Depression Rating ScaleHomovanillic acid levelsSerotonin reuptake inhibitorsDepression Rating ScaleSimilar significant decreaseAntihistamine diphenhydramine hydrochlorideSeparate test sessionsFeelings of worthlessnessConsiderable sedationLoss of interestDepressed patientsDepressive relapseAntidepressant drugsInactive placeboTherapeutic effectTherapeutic mechanismDepressive symptomsCatecholamine metabolitesPlasma 3Remission