2024
Ketamine induces multiple individually distinct whole-brain functional connectivity signatures
Moujaes F, Ji J, Rahmati M, Burt J, Schleifer C, Adkinson B, Savic A, Santamauro N, Tamayo Z, Diehl C, Kolobaric A, Flynn M, Rieser N, Fonteneau C, Camarro T, Xu J, Cho Y, Repovs G, Fineberg S, Morgan P, Seifritz E, Vollenweider F, Krystal J, Murray J, Preller K, Anticevic A. Ketamine induces multiple individually distinct whole-brain functional connectivity signatures. ELife 2024, 13: e84173. PMID: 38629811, PMCID: PMC11023699, DOI: 10.7554/elife.84173.Peer-Reviewed Original ResearchConceptsResponse to ketamineAcute ketamineBehavioral effectsQuantified resting-state functional connectivityEffects of acute ketamineSymptom variationResting-state functional connectivityTreatment-resistant depressionFunctional connectivity signaturesGlobal brain connectivitySingle-subject levelInter-individual variabilityPlacebo-controlled studyFunctional connectivityConnectivity signaturesBrain connectivityHealthy participantsSingle-blind placebo-controlled studyNeural variationsTreatment conditionsKetamineGene expression targetsPharmacological biomarkersPilot awardParvalbuminRecent Advances in the Treatment of Treatment-Resistant Depression: A Narrative Review of Literature Published from 2018 to 2023
Havlik J, Wahid S, Teopiz K, McIntyre R, Krystal J, Rhee T. Recent Advances in the Treatment of Treatment-Resistant Depression: A Narrative Review of Literature Published from 2018 to 2023. Current Psychiatry Reports 2024, 26: 176-213. PMID: 38386251, DOI: 10.1007/s11920-024-01494-4.Peer-Reviewed Original ResearchTreatment of treatment-resistant depressionTreatment-resistant depressionMedication discontinuation ratesTranscranial magnetic stimulationElectroconvulsive therapyPsychiatric approachApproach to treatmentAdjunctive pharmacotherapyIntervention approachesAdjunctive treatmentDiscontinuation ratesMagnetic stimulationGeneralizability resultsDepressionPharmacotherapyInclusion criteriaAntipsychoticsPsychotherapyNarrative reviewKetamine/esketamineSide effectsStudy inclusion criteriaRecent FindingsRecent evidenceDisordersBuprenorphine
2023
Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms
Krystal J, Kavalali E, Monteggia L. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology 2023, 49: 41-50. PMID: 37488280, PMCID: PMC10700627, DOI: 10.1038/s41386-023-01629-w.Peer-Reviewed Original ResearchConceptsMood disordersEffective treatmentN-methyl-D-aspartate receptorsGlutamatergic N-methyl-D-aspartate receptorRapid antidepressant effectsTreatment-resistant depressionKey clinical aspectsRapid antidepressant actionsNovel effective treatmentsSynaptic signaling mechanismsMore effective treatmentsSynaptic plasticity mechanismsOpen channel blockerAntidepressant actionAntidepressant effectsKetamine effectsChannel blockersClinical aspectsClinical practiceNew treatmentsNeuropsychiatric disordersCircuit mechanismsDisordersTreatmentKetamine
2022
Long-term safety of ketamine and esketamine in treatment of depression
Nikayin S, Murphy E, Krystal JH, Wilkinson ST. Long-term safety of ketamine and esketamine in treatment of depression. Expert Opinion On Drug Safety 2022, 21: 777-787. PMID: 35416105, DOI: 10.1080/14740338.2022.2066651.Peer-Reviewed Original ResearchConceptsLong-term safetyClinical trialsRacemic ketamineLong-term safety effectsRapid-acting antidepressant effectsLower urinary tract symptomsKetamine/esketamineTreatment-resistant depressionUrinary tract symptomsCommon side effectsTreatment of depressionLong-term impairmentElevated heart ratePhase three clinical trialsTract symptomsAntidepressant effectsBlood pressureIncreased riskBladder pathologyEsketamineHeart ratePsychiatric disordersSide effectsCognitive impairmentHigh dosesmTORC1 inhibitor effects on rapid ketamine-induced reductions in suicidal ideation in patients with treatment-resistant depression
Averill LA, Averill CL, Gueorguieva R, Fouda S, Sherif M, Ahn KH, Ranganathan M, D'Souza DC, Southwick SM, Sanacora G, Duman RS, Krystal JH, Abdallah CG. mTORC1 inhibitor effects on rapid ketamine-induced reductions in suicidal ideation in patients with treatment-resistant depression. Journal Of Affective Disorders 2022, 303: 91-97. PMID: 35101523, DOI: 10.1016/j.jad.2022.01.104.Peer-Reviewed Original ResearchConceptsAntisuicidal effectsAntidepressant effectsSuicidal ideationKetamine-induced reductionTreatment-resistant depressionLimited treatment optionsCross-over trialMajor depressive episodeOral rapamycinPublic health crisisKetamine administrationTreatment optionsDepressive episodeParent studyOverall severityKetamineTwo weeksBeck ScaleRapamycin complex 1Mechanistic targetPatientsSignificant main effectHealth crisisRobust improvementFuture studies
2019
Maintenance of antidepressant and antisuicidal effects by D-cycloserine among patients with treatment-resistant depression who responded to low-dose ketamine infusion: a double-blind randomized placebo–control study
Chen MH, Cheng CM, Gueorguieva R, Lin WC, Li CT, Hong CJ, Tu PC, Bai YM, Tsai SJ, Krystal JH, Su TP. Maintenance of antidepressant and antisuicidal effects by D-cycloserine among patients with treatment-resistant depression who responded to low-dose ketamine infusion: a double-blind randomized placebo–control study. Neuropsychopharmacology 2019, 44: 2112-2118. PMID: 31421635, PMCID: PMC6898334, DOI: 10.1038/s41386-019-0480-y.Peer-Reviewed Original ResearchConceptsTreatment-resistant depressionAntisuicidal effectsPlacebo groupKetamine infusionDCS groupD-cycloserineDouble-blind randomized placebo-controlled studyN-methyl-D-aspartate (NMDA) glutamate receptorsHamilton Depression Rating Scale scoresLow-dose ketamine infusionRandomized placebo-controlled studyDepression Rating Scale scoresHAMD item 3Single subanesthetic doseInitial clinical responsePlacebo-controlled studyRating Scale scoresClinical responseDose titrationSubanesthetic doseAugmentation treatmentGlutamate receptorsMixed model analysisSuicidal riskScale score
2018
Correction: 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. Correction: Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. Neuropsychopharmacology 2018, 44: 655-656. PMID: 30487654, PMCID: PMC6333826, DOI: 10.1038/s41386-018-0253-z.Peer-Reviewed Original Research
2017
Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment
Abdallah CG, Averill CL, Salas R, Averill LA, Baldwin PR, Krystal JH, Mathew SJ, Mathalon DH. Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2017, 2: 566-574. PMID: 29034354, PMCID: PMC5635826, DOI: 10.1016/j.bpsc.2017.04.006.Peer-Reviewed Original ResearchTreatment-resistant depressionTRD patientsHealthy subjectsHealthy controlsStudy AStudy BEffects of lamotrigineAbility of ketamineGlobal brain connectivityEffects of ketamineFunctional magnetic resonance imagingMagnetic resonance imagingSignificant reductionOral lamotrigineKetamine treatmentKetamine infusionKetamine's mechanismGlutamate transmissionGlutamate neurotransmissionDepression pathophysiologyPharmacological challengeKetamine interactionKetaminePrefrontal connectivityResonance imagingDose-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 Scale
2016
KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Abdallah CG, Adams TG, Kelmendi B, Esterlis I, Sanacora G, Krystal JH. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS. Depression And Anxiety 2016, 33: 689-697. PMID: 27062302, PMCID: PMC4961540, DOI: 10.1002/da.22501.Peer-Reviewed Original ResearchConceptsMajor depressive disorderAntidepressant effectsKetamine's mechanismN-methyl-D-aspartate receptor antagonistRapid-acting antidepressant effectsPrefrontal cortexSingle subanesthetic doseRapid antidepressant effectsTreatment-resistant depressionFull therapeutic effectEfficacy of ketamineKetamine's antidepressant effectsRapid acting antidepressantsFuture clinical prospectsGlutamate surgeTraditional antidepressantsAntidepressant medicationCascade of eventsReceptor antagonistSubanesthetic doseDepressive disorderClinical dataTherapeutic effectTreatment responseLimited efficacy
2014
Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics
Abdallah CG, Sanacora G, Duman RS, Krystal JH. Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics. Annual Review Of Medicine 2014, 66: 1-15. PMID: 25341010, PMCID: PMC4428310, DOI: 10.1146/annurev-med-053013-062946.Peer-Reviewed Original ResearchConceptsRapid antidepressant effectsAntidepressant effectsGlutamate-based antidepressantsTolerability of ketamineRapid-acting antidepressantsTreatment-resistant depressionNeurobiology of depressionPotent antidepressant effectsRapid acting antidepressantsBiology of depressionPotential treatment targetHours of treatmentTreatment targetsKetamineAntidepressantsBiomarker studiesDepressionNeurobiologyTolerability
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