2024
Illusory generalizability of clinical prediction models
Chekroud A, Hawrilenko M, Loho H, Bondar J, Gueorguieva R, Hasan A, Kambeitz J, Corlett P, Koutsouleris N, Krumholz H, Krystal J, Paulus M. Illusory generalizability of clinical prediction models. Science 2024, 383: 164-167. PMID: 38207039, DOI: 10.1126/science.adg8538.Peer-Reviewed Original Research
2023
Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia
Surti T, Ranganathan M, Johannesen J, Gueorguieva R, Deaso E, Kenney J, Krystal J, D'Souza D. Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia. Schizophrenia Research 2023, 256: 36-43. PMID: 37141764, PMCID: PMC10257994, DOI: 10.1016/j.schres.2023.04.010.Peer-Reviewed Original ResearchMeSH KeywordsAntipsychotic AgentsCognitive TrainingDouble-Blind MethodGlycine Plasma Membrane Transport ProteinsHumansNeuronal PlasticitySchizophreniaConceptsGlycine transporter 1Cytochrome P450 2D6 extensive metabolizersGlyT1 inhibitorsWeeks of washoutWeeks of CTMedication adherenceReceptor hypofunctionImpaired neuroplasticityPharmacodynamic variabilityNMDAR functionExtensive metabolizersTreatment periodPsychotic symptomsStable outpatientsCognitive impairmentGlyT1 occupancyTransporter 1CTNeuroplasticityCognitive training strategiesSchizophreniaComputerized CTCognitive performanceAugmentation studiesGreater improvement
2022
Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial.
Citrome L, Preskorn SH, Lauriello J, Krystal JH, Kakar R, Finman J, De Vivo M, Yocca FD, Risinger R, Rajachandran L. Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial. The Journal Of Clinical Psychiatry 2022, 83 PMID: 36198061, DOI: 10.4088/jcp.22m14447.Peer-Reviewed Original ResearchConceptsAcute agitationHours postdoseSchizoaffective disorderTotal scorePrimary efficacy endpointPlacebo-controlled studyAdrenergic receptor agonistFifth Edition criteriaNegative Syndrome ScaleDexmedetomidine groupOral hypoesthesiaStudy medicationDry mouthEfficacy endpointOrthostatic hypotensionRandomized PlaceboAdverse eventsReceptor agonistEdition criteriaDexmedetomidineMean changePEC scoresPlaceboSyndrome ScaleUS sites
2020
Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers
Kantrowitz JT, Grinband J, Goff DC, Lahti AC, Marder SR, Kegeles LS, Girgis RR, Sobeih T, Wall MM, Choo TH, Green MF, Yang YS, Lee J, Horga G, Krystal JH, Potter WZ, Javitt DC, Lieberman JA. Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers. Neuropsychopharmacology 2020, 45: 1842-1850. PMID: 32403118, PMCID: PMC7608251, DOI: 10.1038/s41386-020-0706-z.Peer-Reviewed Original ResearchMeSH KeywordsAntipsychotic AgentsDouble-Blind MethodHealthy VolunteersHumansKetaminePharmaceutical PreparationsSchizophreniaSingle-Blind MethodConceptsDorsal anterior cingulate cortexBrief Psychiatric Rating ScaleTS-134Target engagementHealthy volunteersMetabotropic glutamate receptor 2/3 agonistKetamine-induced psychotic symptomsBPRS positive symptomsDouble-blind conditionsProof of mechanismKetamine-induced changesAntipsychotic drug developmentTreatment of schizophreniaPsychiatric Rating ScaleAnterior cingulate cortexPrimary outcomeClinical symptomsGlutamatergic drugsGlutamate neurotransmissionTotal symptomsClinical assessmentLow dosePsychotic symptomsHigh dosePlacebo dataAssociation of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia
Beck K, Hindley G, Borgan F, Ginestet C, McCutcheon R, Brugger S, Driesen N, Ranganathan M, D’Souza D, Taylor M, Krystal JH, Howes OD. Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia. JAMA Network Open 2020, 3: e204693. PMID: 32437573, PMCID: PMC7243091, DOI: 10.1001/jamanetworkopen.2020.4693.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScalePlacebo conditionPositive symptomsNegative symptomsHealthy participantsMean differenceKetamine administrationPANSS scoresHealthy volunteersPsychotomimetic symptomsTherapeutic useAcute ketamine administrationAcute ketamine challengePlacebo-controlled studyEffect sizeMagnitude of symptomsStudy-level dataPsychiatric Rating ScaleMeta-Analyses (PRISMA) guidelinesPreferred Reporting ItemsAssociation of ketamineNegative Syndrome ScaleSignificant increaseAcute administrationBolus dosesA Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia
Koblan KS, Kent J, Hopkins SC, Krystal JH, Cheng H, Goldman R, Loebel A. A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia. New England Journal Of Medicine 2020, 382: 1497-1506. PMID: 32294346, DOI: 10.1056/nejmoa1911772.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdministration, OralAdultAntipsychotic AgentsDouble-Blind MethodDrug Administration ScheduleFemaleHumansLeast-Squares AnalysisMaleReceptors, Dopamine D2Receptors, G-Protein-CoupledSchizophreniaSchizophrenic PsychologySerotonin 5-HT1 Receptor AgonistsSeverity of Illness IndexTreatment OutcomeConceptsTrace amine-associated receptor 1Week 4Negative Symptom ScaleAcute exacerbationPlacebo groupBrief Negative Symptom ScaleTotal scoreSymptom ScaleClinical Global Impression-Severity ScaleEnd pointPrimary end pointSecondary end pointsSudden cardiac deathPANSS total scoreTreatment of schizophreniaDopamine D2 receptorsTreatment of psychosisType 1A receptorMean total scoreLevels of lipidsGastrointestinal symptomsAdverse eventsCardiac deathExtrapyramidal symptomsPrimary outcome
2018
Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial
Javitt DC, Carter CS, Krystal JH, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Corlett PR, Rothman DL, Mason G, Qiu M, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman JA. Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial. JAMA Psychiatry 2018, 75: 11-19. PMID: 29167877, PMCID: PMC5833531, DOI: 10.1001/jamapsychiatry.2017.3572.Peer-Reviewed Original ResearchConceptsTarget engagement biomarkerKetamine infusionClinical trialsClinical studiesEarly-stage clinical studiesEarly phase clinical studiesTarget engagementFunctional target engagementRecent pivotal trialsFMRI responsesBlood oxygen level-dependent (BOLD) responseUtility of imagingProton magnetic resonance spectroscopySufficient effect sizeLevel-dependent responsesPlacebo infusionPivotal trialsPreclinical evidenceEngagement biomarkersKetamine effectsMean ageBrain glutamateHealthy volunteersMAIN OUTCOMEPsychiatric history
2017
Correlates of Nonimprovement to Pharmacotherapy for Chronic, Antidepressant-Resistant, Military Service–Related Posttraumatic Stress Disorder
Byrne SP, Krystal JH, Rosenheck RA, Vessicchio J, Pietrzak RH. Correlates of Nonimprovement to Pharmacotherapy for Chronic, Antidepressant-Resistant, Military Service–Related Posttraumatic Stress Disorder. Journal Of Clinical Psychopharmacology 2017, 37: 717-721. PMID: 28945664, DOI: 10.1097/jcp.0000000000000777.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntidepressive AgentsAntipsychotic AgentsDrug Therapy, CombinationFemaleHumansMaleMiddle AgedOutcome Assessment, Health CareRandomized Controlled Trials as TopicRisperidoneSeverity of Illness IndexStress Disorders, Post-TraumaticUnited StatesUnited States Department of Veterans AffairsVeteransConceptsPosttraumatic stress disorderAdjunctive risperidoneTreatment-resistant posttraumatic stress disorderClinician-Administered PTSD Scale scoresSymptom clustersStress disorderOriginal treatment regimenFirst-line pharmacotherapySpecific symptom clustersSpecific PTSD symptom clustersVeterans RANDTreatment regimenPharmacotherapeutic effectsHealth SurveyRole functioningPTSD symptom clustersTreat conditionScale scoreGreater severityVariable improvementRisperidoneTargeted pharmacotherapyPlaceboNonimprovementPharmacotherapyMinimal Clinically Important Differences (MCID) in Assessing Outcomes of Post-Traumatic Stress Disorder
Stefanovics EA, Rosenheck RA, Jones KM, Huang G, Krystal JH. Minimal Clinically Important Differences (MCID) in Assessing Outcomes of Post-Traumatic Stress Disorder. Psychiatric Quarterly 2017, 89: 141-155. PMID: 28634644, DOI: 10.1007/s11126-017-9522-y.Peer-Reviewed Original Research
2015
Toward Illness Phase–Specific Pharmacotherapy for Schizophrenia
Krystal JH, Anticevic A. Toward Illness Phase–Specific Pharmacotherapy for Schizophrenia. Biological Psychiatry 2015, 78: 738-740. PMID: 26542740, DOI: 10.1016/j.biopsych.2015.08.017.Peer-Reviewed Original Research
2014
Elucidating the transdiagnostic dimensional structure of trauma-related psychopathology: Findings from VA cooperative study 504 – risperidone treatment for military service related chronic post traumatic stress disorder
Pietrzak RH, Rosenheck RA, Cramer JA, Vessichio JC, Tsai J, Southwick SM, Krystal JH, Group F. Elucidating the transdiagnostic dimensional structure of trauma-related psychopathology: Findings from VA cooperative study 504 – risperidone treatment for military service related chronic post traumatic stress disorder. Journal Of Affective Disorders 2014, 172: 331-336. PMID: 25451434, DOI: 10.1016/j.jad.2014.10.025.Peer-Reviewed Original ResearchSymptom structure and severity: A comparison of responses to the positive and negative syndrome scale (PANSS) between patients with PTSD or schizophrenia
Stefanovics EA, Krystal JH, Rosenheck RA. Symptom structure and severity: A comparison of responses to the positive and negative syndrome scale (PANSS) between patients with PTSD or schizophrenia. Comprehensive Psychiatry 2014, 55: 887-895. PMID: 24602497, DOI: 10.1016/j.comppsych.2014.01.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntipsychotic AgentsChronic DiseaseCombat DisordersDiagnosis, DifferentialDouble-Blind MethodFemaleHumansMaleMiddle AgedPsychiatric Status Rating ScalesPsychometricsRisperidoneSchizophreniaSchizophrenic PsychologyStress Disorders, Post-TraumaticVeteransYoung AdultConceptsPost-traumatic stress disorderNegative Syndrome ScaleSyndrome ScalePTSD samplePlacebo-controlled trialPsychosis-related factorsClinical trial patientsClinical Antipsychotic TrialsT-testSchizophrenia sampleExploratory factor analysisSymptoms of schizophreniaMilitary-related post-traumatic stress disorderSymptom structureAdjunctive risperidoneTrial patientsTraumatic Stress DisorderAntipsychotic TrialsSecondary data analysisSevere symptomsIndependent factorsDepressive factorsPatientsSymptom ratingsStress disorderDifferences in Treatment Effect Among Clinical Subgroups in a Randomized Clinical Trial of Long-Acting Injectable Risperidone and Oral Antipsychotics in Unstable Chronic Schizophrenia
Leatherman SM, Liang MH, Krystal JH, Lew RA, Valley D, Thwin SS, Rosenheck RA. Differences in Treatment Effect Among Clinical Subgroups in a Randomized Clinical Trial of Long-Acting Injectable Risperidone and Oral Antipsychotics in Unstable Chronic Schizophrenia. The Journal Of Nervous And Mental Disease 2014, 202: 13-17. PMID: 24375206, DOI: 10.1097/nmd.0000000000000069.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntipsychotic AgentsChronic DiseaseDrug Administration ScheduleFemaleHospitalizationHumansInjections, IntramuscularMaleMiddle AgedProportional Hazards ModelsPsychotic DisordersQuality of LifeRisk AssessmentRisperidoneSchizophreniaSchizophrenic PsychologySeverity of Illness IndexSubstance-Related DisordersTreatment OutcomeConceptsQuality of lifeOral antipsychoticsOral treatmentInjectable risperidoneCox regressionTreatment effectsLong-Acting Injectable RisperidoneBody mass indexPsychiatric service useSubstance abuse outcomesSubstance use outcomesLAI risperidonePrimary endpointStudy entryWhite patientsClinical outcomesMass indexUnstable patientsMedication compliancePsychiatric rehospitalizationChronic schizophreniaClinical trialsClinical subgroupsPsychiatric hospitalizationPsychiatric symptoms
2012
Capturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans
Moghaddam B, Krystal JH. Capturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans. Schizophrenia Bulletin 2012, 38: 942-949. PMID: 22899397, PMCID: PMC3446228, DOI: 10.1093/schbul/sbs075.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsAntipsychotic AgentsBrief Psychiatric Rating ScaleCerebral CortexDisease Models, AnimalDopamineEmotionsGlutamic AcidHumansKetamineNeurosciencesPhencyclidinePsychoses, Substance-InducedReceptor, Metabotropic Glutamate 5Receptors, Dopamine D2Receptors, Metabotropic GlutamateReceptors, N-Methyl-D-AspartateSchizophreniaSynapsesTranslational Research, BiomedicalConceptsNMDA receptor antagonistReceptor antagonistDopamine hypothesisN-methyl-D-aspartate receptor antagonistGlutamate synaptic functionTranslational neuroscience studiesTreatment of schizophreniaPathophysiology of schizophreniaPotential treatment targetPotential new targetsDopamine antagonistsCortical functionAnimal studiesTreatment targetsClinical testingSynaptic functionAntagonistTranslational toolSchizophreniaTranslational research fundingTranslational researchPotential mechanismsNew targetsAngel dustSystems neuroscienceCost and cost-effectiveness in a randomized trial of long-acting risperidone for schizophrenia.
Barnett PG, Scott JY, Krystal JH, Rosenheck RA. Cost and cost-effectiveness in a randomized trial of long-acting risperidone for schizophrenia. The Journal Of Clinical Psychiatry 2012, 73: 696-702. PMID: 22697193, DOI: 10.4088/jcp.11m07070.Peer-Reviewed Original ResearchMeSH KeywordsAntipsychotic AgentsComparative Effectiveness ResearchCost-Benefit AnalysisDelayed-Action PreparationsDouble-Blind MethodDrug CostsFemaleHealth Care CostsHospitalizationHumansInjectionsKaplan-Meier EstimateMaleMiddle AgedModels, EconometricPsychotic DisordersRisperidoneSchizophreniaUnited StatesVeteransConceptsTotal health care costsHealth care costsLAI risperidoneMedication costsControl groupCare costsVeterans Health Administration patientsHealth care utilizationHealth Related QualityStructured Clinical InterviewUS Medicaid programCase report formsMultisite clinical trialQuality of WellExperimental groupOral antipsychoticsAdverse eventsCare utilizationInjectable risperidoneOutpatient costsHospitalization costsClinical trialsRelated qualityLAI groupPhysician's choice
2011
Advancing drug discovery for schizophrenia
Marder SR, Roth B, Sullivan PF, Scolnick EM, Nestler EJ, Geyer MA, Welnberger DR, Karayiorgou M, Guidotti A, Gingrich J, Akbarian S, Buchanan RW, Lieberman JA, Conn PJ, Haggarty SJ, Law AJ, Campbell B, Krystal JH, Moghaddam B, Saw A, Caron MG, George SR, Allen JA, Solis M. Advancing drug discovery for schizophrenia. Annals Of The New York Academy Of Sciences 2011, 1236: 30-43. PMID: 22032400, PMCID: PMC3787879, DOI: 10.1111/j.1749-6632.2011.06216.x.Peer-Reviewed Original ResearchLong-Acting Risperidone and Oral Antipsychotics in Unstable Schizophrenia
Rosenheck RA, Krystal JH, Lew R, Barnett PG, Fiore L, Valley D, Thwin SS, Vertrees JE, Liang MH. Long-Acting Risperidone and Oral Antipsychotics in Unstable Schizophrenia. New England Journal Of Medicine 2011, 364: 842-851. PMID: 21366475, DOI: 10.1056/nejmoa1005987.Peer-Reviewed Original ResearchConceptsInjectable risperidoneOral antipsychoticsQuality of lifeSchizoaffective disorderPsychiatrist's choiceSecond-generation antipsychotic agentsMore adverse eventsMore extrapyramidal symptomsPrimary end pointNeurologic side effectsExtrapyramidal adverse effectsRate of hospitalizationVeterans Affairs systemSocial Performance ScaleAdverse eventsExtrapyramidal symptomsOral treatmentAntipsychotic agentsUnstable diseasePsychiatric symptomsHigh riskHospitalizationSide effectsPatientsPsychiatric hospitalChallenges in the design and conduct of controlled clinical effectiveness trials in schizophrenia
Rosenheck RA, Krystal JH, Lew R, Barnett PG, Thwin SS, Fiore L, Valley D, Huang GD, Neal C, Vertrees JE, Liang MH. Challenges in the design and conduct of controlled clinical effectiveness trials in schizophrenia. Clinical Trials 2011, 8: 196-204. PMID: 21270143, DOI: 10.1177/1740774510392931.Peer-Reviewed Original ResearchConceptsSchizo-affective disorderAntipsychotic medicationUsual careMedication adherenceEffectiveness trialCommon co-morbid illnessesCo-morbid illnessHigh-risk patientsComparative effectiveness trialClinical effectiveness trialVeterans Health AdministrationNew antipsychotic medicationsTreatment of schizophreniaPsychiatric inpatient hospitalizationQuality of lifeHealth care costsElectronic medical recordsLong-term trialsPatient's psychiatristPrimary endpointSecondary endpointsFirst hospitalizationRecent hospitalizationInjectable risperidoneUnstable patients
2010
Potential Psychiatric Applications of Metabotropic Glutamate Receptor Agonists and Antagonists
Krystal JH, Mathew SJ, D’Souza D, Garakani A, Gunduz-Bruce H, Charney DS. Potential Psychiatric Applications of Metabotropic Glutamate Receptor Agonists and Antagonists. CNS Drugs 2010, 24: 669-693. PMID: 20658799, DOI: 10.2165/11533230-000000000-00000.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPreliminary clinical trialsPositive allosteric modulatorsPsychiatric disordersClinical trialsAnimal modelsAllosteric modulatorsGroup II mGluR agonistGroup IMetabotropic glutamate receptor agonistAnxiety disordersPotential psychiatric applicationsGlutamate receptor agonistsMetabotropic glutamate receptorsTreatment of schizophreniaRole of glutamateForm of depressionMGluR agonistAntidepressant propertiesMGluR5 agonistReceptor agonistGlutamate receptorsMood disordersArea of schizophreniaPromising agentAgonists
2009
The efficacies of clozapine and haloperidol in refractory schizophrenia are related to DTNBP1 variation
Zuo L, Luo X, Krystal JH, Cramer J, Charney DS, Gelernter J. The efficacies of clozapine and haloperidol in refractory schizophrenia are related to DTNBP1 variation. Pharmacogenetics And Genomics 2009, 19: 437-446. PMID: 19369910, PMCID: PMC2857717, DOI: 10.1097/fpc.0b013e32832b9cfc.Peer-Reviewed Original Research