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
DSM-5 Criterion-A-Based Trauma Types in Service Members and Veterans Seeking Treatment for Posttraumatic Stress Disorder
Benfer N, Grunthal B, Dondanville K, Young-McCaughan S, Blankenship A, Abdallah C, Back S, Flanagan J, Foa E, Fox P, Krystal J, Marx B, McGeary D, McLean C, Pruiksma K, Resick P, Roache J, Shiroma P, Sloan D, Taylor D, Wachen J, López-Roca A, Nicholson K, Schobitz R, Schrader C, Sharrieff A, Yarvis J, Mintz J, Keane T, Peterson A, Litz B. DSM-5 Criterion-A-Based Trauma Types in Service Members and Veterans Seeking Treatment for Posttraumatic Stress Disorder. Psychological Trauma Theory Research Practice And Policy 2023, 16: 1218-1228. PMID: 37410416, PMCID: PMC10770283, DOI: 10.1037/tra0001537.Peer-Reviewed Original ResearchPosttraumatic stress disorderTrauma typesBehavioral health problemsHealth problemsStress disorderMoral injuryParticipants' ratingsLife threatAftermath of violenceMental health problemsDSM-5 criteriaTraumatic eventsParticipants' endorsementClinical trialsDifferent traumasTyping schemeTraumatic lossAssessor judgementsService membersTraumaClinical researchersParticipantsUnique contextInjuryMilitary personnel
2022
Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode
Rhee TG, Shim SR, Forester BP, Nierenberg AA, McIntyre RS, Papakostas GI, Krystal JH, Sanacora G, Wilkinson ST. Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode. JAMA Psychiatry 2022, 79: 1162-1172. PMID: 36260324, PMCID: PMC9582972, DOI: 10.1001/jamapsychiatry.2022.3352.Peer-Reviewed Original ResearchConceptsStandardized mean differenceMajor depressive episodeSerious adverse eventsElectroconvulsive therapyAdverse eventsDepressive episodeClinical trialsDepression severityEfficacy outcomesSystematic reviewUnique adverse effect profileMeta-analyses (PRISMA) reporting guidelinesSafety of ketamineAdverse effect profileData extractionEuropean clinical trialsDiagnosis of depressionModerate methodological qualityMedical Subject Headings termsPreferred Reporting ItemsCognition/memoryRandom-effects modelSubject Headings termsAcute phaseEffect profileTechnology and Mental Health: State of the Art for Assessment and Treatment
Harvey PD, Depp CA, Rizzo AA, Strauss GP, Spelber D, Carpenter LL, Kalin NH, Krystal JH, McDonald WM, Nemeroff CB, Rodriguez CI, Widge AS, Torous J. Technology and Mental Health: State of the Art for Assessment and Treatment. American Journal Of Psychiatry 2022, 179: 897-914. PMID: 36200275, DOI: 10.1176/appi.ajp.21121254.Peer-Reviewed Original ResearchConceptsHigh-quality evidenceEcological momentary assessmentTechnology-based interventionsMental health applicationsClinical trialsTreatment strategiesCognitive trainingFunctional capacityDrug AdministrationSystematic reviewVirtual reality approachMomentary assessmentU.S. FoodMental healthFunctional skillsTechnology-based assessmentInterventionTechnology-based approachesTreatmentAssessmentHealth applicationsPhysiological parametersReality approachReviewEmotionsCorrection to: 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. Correction to: 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: 1583-1584. PMID: 35545665, PMCID: PMC9205895, DOI: 10.1038/s41386-022-01339-9.Peer-Reviewed Original ResearchLong-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 dosesDose-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
2021
Risks and Benefits of Cannabis and Cannabinoids in Psychiatry
Hill KP, Gold MS, Nemeroff CB, McDonald W, Grzenda A, Widge AS, Rodriguez C, Kraguljac NV, Krystal JH, Carpenter LL. Risks and Benefits of Cannabis and Cannabinoids in Psychiatry. American Journal Of Psychiatry 2021, 179: 98-109. PMID: 34875873, DOI: 10.1176/appi.ajp.2021.21030320.Peer-Reviewed Original ResearchConceptsPsychiatric disordersRandomized double-blind placebo-controlled trialDouble-blind placebo-controlled trialTherapeutic useEvidence basePlacebo-controlled trialManagement of painBenefits of cannabisSearch of PubMedMental health cliniciansCurrent evidence basePotential side effectsSpecific medical conditionsPsychiatric indicationsFDA indicationClinical trialsHealth cliniciansMedical conditionsReference listsSide effectsChronic cannabisPsychotic disordersDrug AdministrationAdditional articlesMedicinal cannabisDesign of the national adaptive trial for PTSD-related insomnia (NAP study), VA cooperative study program (CSP) #2016
Krystal JH, Chow B, Vessicchio J, Henrie AM, Neylan TC, Krystal AD, Marx BP, Xu K, Jindal RD, Davis LL, Schnurr PP, Stein MB, Thase ME, Ventura B, Huang GD, Shih MC, Team T. Design of the national adaptive trial for PTSD-related insomnia (NAP study), VA cooperative study program (CSP) #2016. Contemporary Clinical Trials 2021, 109: 106540. PMID: 34416369, DOI: 10.1016/j.cct.2021.106540.Peer-Reviewed Original ResearchConceptsCooperative Studies ProgramInsomnia medicationsMedical CenterRandomized placebo-controlled clinical trialPlacebo-controlled clinical trialVeterans Affairs Medical CenterVA Cooperative Studies ProgramPrimary outcome measureVA Medical CenterInsomnia Severity IndexAdaptive trialsPosttraumatic stress disorderFuture biomarker developmentStudy armsBiochemical predictorsEffective pharmacotherapyClinical trialsOutcome measuresTreatment responseInterim analysisRecruitment targetInsomniaPhone contactStress disorderBiomarker development
2020
Characteristics of Ongoing Clinical Trials for Alcohol Use Disorder Registered on ClinicalTrials.gov
Wallach JD, Krystal JH, Ross JS, O’Malley S. Characteristics of Ongoing Clinical Trials for Alcohol Use Disorder Registered on ClinicalTrials.gov. JAMA Psychiatry 2020, 77: 1081-1084. PMID: 32459295, PMCID: PMC7254444, DOI: 10.1001/jamapsychiatry.2020.1167.Peer-Reviewed Original ResearchA robust and reproducible connectome fingerprint of ketamine is highly associated with the connectomic signature of antidepressants
Abdallah CG, Ahn KH, Averill LA, Nemati S, Averill CL, Fouda S, Ranganathan M, Morgan PT, D’Souza D, Mathalon DH, Krystal JH, Driesen NR. A robust and reproducible connectome fingerprint of ketamine is highly associated with the connectomic signature of antidepressants. Neuropsychopharmacology 2020, 46: 478-485. PMID: 32967000, PMCID: PMC7852889, DOI: 10.1038/s41386-020-00864-9.Peer-Reviewed Original ResearchConceptsConnectome fingerprintN-methyl-d-aspartate modulatorsNovel rapid-acting antidepressantsMajor depressive disorder patientsMechanism of antidepressantsWeeks of sertralineRapid-acting antidepressantsMagnetic resonance imaging studyDepressive disorder patientsExecutive networkEffects of ketamineLongitudinal functional magnetic resonance imaging studyResonance imaging studyFunctional magnetic resonance imaging studyBrain functional connectivityCohort AIntravenous infusionSubanesthetic doseClinical trialsNormal salineDisorder patientsConnectomics signaturesBrain circuitryKetamineImaging studiesSystematic review and meta‐analysis of the moderating effect of rs1799971 in OPRM1, the mu‐opioid receptor gene, on response to naltrexone treatment of alcohol use disorder
Hartwell EE, Feinn R, Morris PE, Gelernter J, Krystal J, Arias AJ, Hoffman M, Petrakis I, Gueorguieva R, Schacht JP, Oslin D, Anton RF, Kranzler HR. Systematic review and meta‐analysis of the moderating effect of rs1799971 in OPRM1, the mu‐opioid receptor gene, on response to naltrexone treatment of alcohol use disorder. Addiction 2020, 115: 1426-1437. PMID: 31961981, PMCID: PMC7340566, DOI: 10.1111/add.14975.Peer-Reviewed Original ResearchConceptsAsn40Asp single-nucleotide polymorphismRandomized clinical trialsAlcohol use disorderNaltrexone treatmentMu-opioid receptor geneUse disordersSingle nucleotide polymorphismsPlacebo-controlled randomized clinical trialsSystematic reviewPublication biasOpioid receptor antagonist naltrexoneWide inter-individual variabilityHeavy drinkingRisk of biasNaltrexone treatment responseReceptor geneRandom-effects modelAlcohol consumption outcomesAntagonist naltrexoneInter-individual variabilityStudy criteriaClinical trialsNucleotide polymorphismsTreatment responseMinor allele
2019
Selective serotonin reuptake inhibitors and benzodiazepines in panic disorder: A meta-analysis of common side effects in acute treatment
Quagliato LA, Cosci F, Shader RI, Silberman EK, Starcevic V, Balon R, Dubovsky SL, Salzman C, Krystal JH, Weintraub SJ, Freire RC, Nardi AE, Benzodiazepines I. Selective serotonin reuptake inhibitors and benzodiazepines in panic disorder: A meta-analysis of common side effects in acute treatment. Journal Of Psychopharmacology 2019, 33: 1340-1351. PMID: 31304840, DOI: 10.1177/0269881119859372.Peer-Reviewed Original ResearchConceptsSelective serotonin reuptake inhibitorsSerotonin reuptake inhibitorsMore adverse effectsPD treatmentPanic disorderReuptake inhibitorsRisk factorsClinical trialsAdverse effectsCochrane Central RegisterAdverse event ratesCommon side effectsShort-term treatmentClass of drugsWeb of ScienceAbnormal ejaculationLibido reductionDry mouthAdverse eventsCentral RegisterPharmacologic treatmentSSRI treatmentAcute treatmentControlled TrialsPrimary outcomeEnhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development
Kaffman A, White JD, Wei L, Johnson FK, Krystal JH. Enhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development. Methods In Molecular Biology 2019, 2011: 3-22. PMID: 31273690, PMCID: PMC6895673, DOI: 10.1007/978-1-4939-9554-7_1.Peer-Reviewed Original ResearchConceptsPreclinical researchAnimal modelsPsychiatric conditionsLower clinical success ratesClinical success rateCommon psychiatric conditionsPsychiatric clinical trialsClinical trialsNew pharmacotherapiesMore effective interventionsPreclinical workPsychiatric disordersPsychiatric pathophysiologyMental illnessSystematic reviewEffective interventionsAnimal experimentsDrug development processSuccess rateDrug developmentHuman psychopathologyPharmaceutical companiesPredictive validityLarge pharmaceutical companiesAnimalsRepeated ketamine infusions for antidepressant-resistant PTSD: Methods of a multicenter, randomized, placebo-controlled clinical trial
Abdallah CG, Roache JD, Averill LA, Young-McCaughan S, Martini B, Gueorguieva R, Amoroso T, Southwick SM, Guthmiller K, López-Roca AL, Lautenschlager K, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH, PTSD F. Repeated ketamine infusions for antidepressant-resistant PTSD: Methods of a multicenter, randomized, placebo-controlled clinical trial. Contemporary Clinical Trials 2019, 81: 11-18. PMID: 30999057, DOI: 10.1016/j.cct.2019.04.009.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStudy drugClinical trialsTherapeutic effectPharmacotherapy of PTSDFirst placebo-controlled trialPlacebo-controlled clinical trialActive duty military populationDose-related efficacyMedication treatment optionsPlacebo-controlled trialDose-related effectsNovel neural mechanismActive duty militaryKetamine infusionSerotonergic antidepressantsEligible participantsTreatment optionsCase reportNew drug developmentOnly trialSustained reductionVeteran populationDrug AdministrationPilot evidence
2018
Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects
D’Souza D, Carson RE, Driesen N, Johannesen J, Ranganathan M, Krystal JH, Ahn K, Bielen K, Carbuto M, Deaso E, D’Souza D, Ranganathan M, Naganawa M, Ranganathan M, D’Souza D, Nabulsi N, Zheng M, Lin S, Huang Y, Carson R, Driesen N, Ahn K, Morgan P, Suckow R, He G, McCarthy G, Krystal J, Johannesen J, Kenney J, Gelernter J, Gueorguieva R, Pittman B. Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects. Biological Psychiatry 2018, 84: 413-421. PMID: 29499855, PMCID: PMC6068006, DOI: 10.1016/j.biopsych.2017.12.019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzabicyclo CompoundsBrainCognitive DysfunctionDose-Response Relationship, DrugDouble-Blind MethodFemaleGlycine Plasma Membrane Transport ProteinsHumansImidazolesKetamineLong-Term PotentiationMagnetic Resonance ImagingMaleMemory, Short-TermMiddle AgedPositron-Emission TomographySchizophreniaYoung AdultConceptsHealthy control subjectsLong-term potentiationSchizophrenia patientsControl subjectsCognitive impairmentClinical trialsGlyT1 occupancyN-methyl-D-aspartate receptor functionGlycine transporter-1 inhibitorKetamine-induced disruptionKetamine-induced effectsFunctional magnetic resonance imagingMagnetic resonance imagingPositron emission tomographyMemory-related activationF-MKSubstudy 1Schizophrenia subjectsResonance imagingReceptor functionCortical regionsEmission tomographyTarget engagementPotentiationSchizophreniaUtility 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
Ketamine: A Promising Rapid-Acting Antidepressant
Wilkinson S, Ostroff R, Katz R, Krystal J. Ketamine: A Promising Rapid-Acting Antidepressant. 2017, 223-239. DOI: 10.1007/978-981-10-6577-4_16.Peer-Reviewed Original ResearchMood disordersDeficiency hypothesisInitiation of therapyRapid antidepressant effectsRapid acting antidepressantsEvidence-based treatmentsLong-term riskMood disorders researchRelapse prevention strategiesEfficient therapeutic targetMechanism of actionOral antidepressantsAntidepressant effectsGlutamatergic receptorsGlutamatergic systemNovel antidepressantsSingle doseClinical trialsKetamine exposureRelated symptomsLong-term effectsPsychiatric disordersPrevention strategiesTherapeutic targetDrug AdministrationMecamylamine treatment for alcohol dependence: a randomized controlled trial
Petrakis IL, Ralevski E, Gueorguieva R, O'Malley SS, Arias A, Sevarino KA, Jane JS, O'Brien E, Krystal JH. Mecamylamine treatment for alcohol dependence: a randomized controlled trial. Addiction 2017, 113: 6-14. PMID: 28710873, PMCID: PMC5725262, DOI: 10.1111/add.13943.Peer-Reviewed Original ResearchConceptsHeavy drinking daysDrinking daysAlcohol use disorderUse disordersAlcohol consumptionAlcohol dependenceDouble-blind clinical trialNicotinic acetylcholine receptor antagonistWeeks of treatmentAcetylcholine receptor antagonistCurrent alcohol dependenceSignificant differencesTreatment-seeking smokersMecamylamine treatmentPlacebo groupMonth 3Primary outcomeSmoking statusNicotine withdrawalReceptor antagonistNovel pharmacotherapiesClinical trialsManagement therapyMecamylamineTreatment groupsTrajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis
Gueorguieva R, Chekroud AM, Krystal JH. Trajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis. The Lancet Psychiatry 2017, 4: 230-237. PMID: 28189575, PMCID: PMC5340978, DOI: 10.1016/s2215-0366(17)30038-x.Peer-Reviewed Original ResearchConceptsActive medicationActive treatmentClinical trialsDepression severityHamilton Depression Rating Scale scoresDepression Rating Scale scoresClinical Global Impression scoresIndividual patient-level dataDouble-blind treatmentPlacebo-controlled trialPatterns of relapseGlobal Impression scoresIndividual patient dataPrevention of relapseTrajectory class membershipTreatment of depressionMajor depressive disorderRating Scale scoresPatient-level dataPost-traumatic stress disorderTreatment discontinuationAntidepressant treatmentClinical responseAlcohol Research CenterAntidepressant medication