2020
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
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
Influence of combined treatment with naltrexone and memantine on alcohol drinking behaviors: a phase II randomized crossover trial
Krishnan-Sarin S, O’Malley S, Franco N, Cavallo DA, Tetrault JM, Shi J, Gueorguieva R, Pittman B, Krystal JH. Influence of combined treatment with naltrexone and memantine on alcohol drinking behaviors: a phase II randomized crossover trial. Neuropsychopharmacology 2019, 45: 319-326. PMID: 31590179, PMCID: PMC6901445, DOI: 10.1038/s41386-019-0536-z.Peer-Reviewed Original ResearchConceptsAlcohol drinking behaviorFirst treatment periodTreatment periodNumber of drinksCrossover trialDrinking behaviorEfficacy of naltrexoneOpioid antagonist naltrexoneNMDA antagonist memantinePositive family historyDay treatment periodSelf-administration periodAlcohol-induced stimulationAd lib accessMemantine treatmentAntagonist naltrexoneOpioid systemFamily historyNTXPriming drinkMemantineNaltrexoneAlcohol cravingHeavy drinkersAlcohol dependenceRigorous Trial Design Is Essential to Understand the Role of Opioid Receptors in Ketamine’s Antidepressant Effect—Reply
Krystal JH, Yoon G, Petrakis IL. Rigorous Trial Design Is Essential to Understand the Role of Opioid Receptors in Ketamine’s Antidepressant Effect—Reply. JAMA Psychiatry 2019, 76: 658-659. PMID: 31042270, DOI: 10.1001/jamapsychiatry.2019.0763.Peer-Reviewed Original ResearchAssociation of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder
Yoon G, Petrakis IL, Krystal JH. Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder. JAMA Psychiatry 2019, 76: 337-338. PMID: 30624551, PMCID: PMC6439824, DOI: 10.1001/jamapsychiatry.2018.3990.Peer-Reviewed Original Research
2013
Temporal patterns of adherence to medications and behavioral treatment and their relationship to patient characteristics and treatment response
Gueorguieva R, Wu R, Krystal JH, Donovan D, O'Malley SS. Temporal patterns of adherence to medications and behavioral treatment and their relationship to patient characteristics and treatment response. Addictive Behaviors 2013, 38: 2119-2127. PMID: 23435273, PMCID: PMC3595348, DOI: 10.1016/j.addbeh.2013.01.024.Peer-Reviewed Original ResearchConceptsPercent heavy drinking daysAdherence trajectoriesExcellent adherersPercent days abstinentPatient characteristicsMedication adherenceTreatment outcomesMedication adherence trajectoriesPatterns of treatmentHeavy drinking daysPatterns of adherenceExcellent medication adherenceLack of benefitTrajectories of adherenceIntervention main effectsActive medicationAdverse eventsPharmacologic treatmentHigher percent days abstinentTreatment adherenceTreatment modalitiesWorse outcomesTreatment responseDays abstinentDrinking days
2011
Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence
Petrakis IL, Ralevski E, Desai N, Trevisan L, Gueorguieva R, Rounsaville B, Krystal JH. Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence. Neuropsychopharmacology 2011, 37: 996-1004. PMID: 22089316, PMCID: PMC3280636, DOI: 10.1038/npp.2011.283.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderSerotonin uptake inhibitorNorepinephrine uptake inhibitorUptake inhibitorAlcohol dependenceMale veteransTreatment of PTSDUse outcomesSymptoms of PTSDDouble-blind conditionsMain outcome measuresEvidence of efficacyComorbid alcohol dependenceCurrent diagnostic criteriaAlcohol use disorderAlcohol use outcomesComorbid conditionsAdjunctive efficacyOutcome measuresOnly FDADiagnostic criteriaUse disordersClinical advantagesAlcohol consumptionDrug AdministrationBaseline trajectories of heavy drinking and their effects on postrandomization drinking in the COMBINE Study: empirically derived predictors of drinking outcomes during treatment
Gueorguieva R, Wu R, Donovan D, Rounsaville BJ, Couper D, Krystal JH, O’Malley S. Baseline trajectories of heavy drinking and their effects on postrandomization drinking in the COMBINE Study: empirically derived predictors of drinking outcomes during treatment. Alcohol 2011, 46: 121-131. PMID: 21925828, PMCID: PMC3266454, DOI: 10.1016/j.alcohol.2011.08.008.Peer-Reviewed Original ResearchConceptsDaily heavy drinkersFrequent heavy drinkersHeavy drinkersHeavy drinkingDrinking outcomesAlcohol-dependent patientsBehavioral intervention studyHeavy drinking trajectoriesSummary drinking measuresBaseline characteristicsActive treatmentSevere baselineCombined PharmacotherapiesWorse outcomesPharmacological interventionsCOMBINE StudyIntervention studiesPatientsTreatment factorsDrinkersOutcomesTrajectory membershipDrinking measuresTreatment effectsDrinking
2010
Baseline Trajectories of Drinking Moderate Acamprosate and Naltrexone Effects in the COMBINE Study
Gueorguieva R, Wu R, Donovan D, Rounsaville BJ, Couper D, Krystal JH, O’Malley S. Baseline Trajectories of Drinking Moderate Acamprosate and Naltrexone Effects in the COMBINE Study. Alcohol Clinical And Experimental Research 2010, 35: 523-531. PMID: 21143249, PMCID: PMC3062945, DOI: 10.1111/j.1530-0277.2010.01369.x.Peer-Reviewed Original Research
2009
Naltrexone and combined behavioral intervention effects on trajectories of drinking in the COMBINE study
Gueorguieva R, Wu R, Donovan D, Rounsaville BJ, Couper D, Krystal JH, O’Malley S. Naltrexone and combined behavioral intervention effects on trajectories of drinking in the COMBINE study. Drug And Alcohol Dependence 2009, 107: 221-229. PMID: 19969427, PMCID: PMC2821955, DOI: 10.1016/j.drugalcdep.2009.10.017.Peer-Reviewed Original Research
2008
Treatment implications: using neuroscience to guide the development of new pharmacotherapies for alcoholism.
Krishnan-Sarin S, O'Malley S, Krystal JH. Treatment implications: using neuroscience to guide the development of new pharmacotherapies for alcoholism. Alcohol Research 2008, 31: 400-7. PMID: 23584013, PMCID: PMC3860468.Peer-Reviewed Original ResearchConceptsAlcohol dependenceCurrent treatment optionsAlcohol-drinking behaviorDifferent neurochemical systemsAdjunctive treatmentModest efficacyTreatment optionsNew medicationsNew pharmacotherapiesMedicationsHealth problemsNeurochemical systemsPharmacotherapyTreatmentGreat needCertain genesNaltrexoneAlcoholismDisulfiramDrinkers
2007
Naltrexone Is Associated With Reduced Drinking by Alcohol Dependent Patients Receiving Antidepressants for Mood and Anxiety Symptoms: Results From VA Cooperative Study No. 425, “Naltrexone in the Treatment of Alcoholism”
Krystal JH, Gueorguieva R, Cramer J, Collins J, Rosenheck R, Team T. Naltrexone Is Associated With Reduced Drinking by Alcohol Dependent Patients Receiving Antidepressants for Mood and Anxiety Symptoms: Results From VA Cooperative Study No. 425, “Naltrexone in the Treatment of Alcoholism”. Alcohol Clinical And Experimental Research 2007, 32: 85-91. PMID: 18070245, DOI: 10.1111/j.1530-0277.2007.00555.x.Peer-Reviewed Original ResearchConceptsEfficacy of naltrexoneGroup of patientsAlcohol-dependent patientsAntidepressant medicationDependent patientsMood symptomsDrinking daysPrescription of antidepressantsAnxiety symptomsVA Medical CenterPercent drinking daysSevere mood symptomsTreatment of alcoholismStep Facilitation TherapyDrinking-related outcomesNaltrexone prescriptionStudy medicationSignificant mood symptomsStudy patientsAntidepressant treatmentStudy entryComorbid conditionsComorbid moodMedical CenterNaltrexoneFamily History of Alcoholism Influences Naltrexone-Induced Reduction in Alcohol Drinking
Krishnan-Sarin S, Krystal JH, Shi J, Pittman B, O’Malley S. Family History of Alcoholism Influences Naltrexone-Induced Reduction in Alcohol Drinking. Biological Psychiatry 2007, 62: 694-697. PMID: 17336941, DOI: 10.1016/j.biopsych.2006.11.018.Peer-Reviewed Original ResearchConceptsAlcohol drinkingFamily historyDrinking periodDose of naltrexoneSignificant clinical predictorsNaltrexone therapyClinical predictorsNaltrexone dosePriming doseMale drinkersNaltrexoneAlcohol-dependent participantsSecondary analysisDoseAlcoholic drinksDrinkingAlcoholismDrinkersDrinksDaysTotal numberParticipantsTherapyOpioid Receptor Gene (OPRM1, OPRK1, and OPRD1) Variants and Response to Naltrexone Treatment for Alcohol Dependence: Results From the VA Cooperative Study
Gelernter J, Gueorguieva R, Kranzler HR, Zhang H, Cramer J, Rosenheck R, Krystal JH, Group T. Opioid Receptor Gene (OPRM1, OPRK1, and OPRD1) Variants and Response to Naltrexone Treatment for Alcohol Dependence: Results From the VA Cooperative Study. Alcohol Clinical And Experimental Research 2007, 31: 555-563. PMID: 17374034, DOI: 10.1111/j.1530-0277.2007.00339.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismConfidence IntervalsDNADouble-Blind MethodExonsFemaleGenetic VariationGenotypeHumansLinear ModelsLogistic ModelsMaleMiddle AgedNaltrexoneNarcotic AntagonistsOdds RatioProportional Hazards ModelsPsychiatric Status Rating ScalesReceptors, Opioid, deltaReceptors, Opioid, kappaReceptors, Opioid, muSmokingTreatment OutcomeUnited StatesUnited States Department of Veterans AffairsConceptsAlcohol dependenceOpioid receptorsTreatment responseVA Cooperative StudyRate of relapsePredictors of responseAlcohol-dependent male subjectsMu-opioid receptorsKappa-opioid receptorsCourse of treatmentShort-term treatmentReceptor gene variantsOpioid receptor geneAsn40Asp polymorphismAvailable medicationsNaltrexone treatmentSpecific pharmacotherapyPretreatment numberDrug naltrexoneNaltrexoneMale subjectsCooperative StudyRelapseHeavy drinkingIndividual single nucleotide polymorphismsNew Insights into the Efficacy of Naltrexone Based on Trajectory-Based Reanalyses of Two Negative Clinical Trials
Gueorguieva R, Wu R, Pittman B, Cramer J, Rosenheck RA, O’Malley S, Krystal JH. New Insights into the Efficacy of Naltrexone Based on Trajectory-Based Reanalyses of Two Negative Clinical Trials. Biological Psychiatry 2007, 61: 1290-1295. PMID: 17224132, PMCID: PMC1952242, DOI: 10.1016/j.biopsych.2006.09.038.Peer-Reviewed Original Research
2006
Potentiation of Low Dose Ketamine Effects by Naltrexone: Potential Implications for the Pharmacotherapy of Alcoholism
Krystal JH, Madonick S, Perry E, Gueorguieva R, Brush L, Wray Y, Belger A, D'Souza DC. Potentiation of Low Dose Ketamine Effects by Naltrexone: Potential Implications for the Pharmacotherapy of Alcoholism. Neuropsychopharmacology 2006, 31: 1793-1800. PMID: 16395307, DOI: 10.1038/sj.npp.1300994.Peer-Reviewed Original ResearchConceptsNMDA glutamate receptorsNMDA receptor antagonismKetamine doseReceptor antagonismGlutamate receptorsKetamine effectsProtective effectPlacebo-controlled human laboratory studyOpiate receptor antagonismEfficacy of naltrexoneDose-related fashionNMDA receptor antagonist effectsReceptor antagonist effectsTotal PANSS scoreHuman laboratory studiesPharmacotherapy of alcoholismTreatment of alcoholismHealthy human subjectsHigher ketamine doseNegative Syndrome ScaleLower ketamine doseSignificant behavioral effectsSubanesthetic dosePANSS scoresEthanol drink
2003
Naltrexone augmentation of neuroleptic treatment in alcohol abusing patients with schizophrenia
Petrakis IL, O’Malley S, Rounsaville B, Poling J, McHugh-Strong C, Krystal JH, VA Naltrexone Study Collaboration Group. Naltrexone augmentation of neuroleptic treatment in alcohol abusing patients with schizophrenia. Psychopharmacology 2003, 172: 291-297. PMID: 14634716, DOI: 10.1007/s00213-003-1658-9.Peer-Reviewed Original ResearchConceptsFederal Drug AdministrationSide effectsDrinking daysAlcohol dependenceDouble-blind fashionEfficacy of naltrexoneAbnormal involuntary movementsComorbid alcohol dependenceHeavy drinking daysTreatment of alcoholismSymptoms of schizophreniaRelapse prevention strategiesNegative Symptom ScaleNaltrexone augmentationTime-line follow-back methodNeuroleptic medicationNeuroleptic treatmentEffective medicationsMedication complianceComorbid schizophreniaOutpatient studyWeekly therapyEffective pharmacotherapyConclusionsThese dataInvoluntary movementsMedication Compliance Feedback and Monitoring in a Clinical Trial: Predictors and Outcomes
Cramer J, Rosenheck R, Kirk G, Krol W, Krystal J, 425 F. Medication Compliance Feedback and Monitoring in a Clinical Trial: Predictors and Outcomes. Value In Health 2003, 6: 566-573. PMID: 14627063, DOI: 10.1046/j.1524-4733.2003.65269.x.Peer-Reviewed Original ResearchConceptsMedication complianceClinical trialsLong-term clinical trialsHigh medication complianceVA Cooperative StudyMonths of treatmentOverall compliance rateAlcohol-dependent patientsPredictors of complianceMedication event monitoringMeasures of complianceDaily naltrexonePlacebo groupMulticenter trialPoor complianceGood compliersTreatment groupsCompliance dataBetter outcomesDrinking daysNaltrexoneCompliance rateCooperative StudyDosesTrials
2001
Naltrexone in the Treatment of Alcohol Dependence
Krystal J, Cramer J, Krol W, Kirk G, Rosenheck R. Naltrexone in the Treatment of Alcohol Dependence. New England Journal Of Medicine 2001, 345: 1734-1739. PMID: 11742047, DOI: 10.1056/nejmoa011127.Peer-Reviewed Original ResearchConceptsMonths of placeboSevere alcohol dependenceAlcohol dependencePlacebo-controlled evaluationUse of naltrexoneOpiate receptor antagonistTreatment of menSignificant differencesPercentage of daysStudy medicationNaltrexone groupPlacebo groupNumber of drinksAlcoholics Anonymous meetingsPsychosocial treatmentsNaltrexoneDrug AdministrationPatientsMonthsIndividual counselingNumber of daysPlaceboTreatmentWeeksDays
1998
Naltrexone Augmentation of Neuroleptics in Schizophrenia
Sernyak M, Glazer W, Heninger G, Charney D, Woods S, Petrakis I, Krystal J, Price L. Naltrexone Augmentation of Neuroleptics in Schizophrenia. Journal Of Clinical Psychopharmacology 1998, 18: 248-251.. PMID: 9617985, DOI: 10.1097/00004714-199806000-00011.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleTotal BPRS scoreBPRS scoresNegative symptomsAddition of naltrexoneBPRS subscale scoresOngoing neuroleptic treatmentSingle-blind basisPlacebo-controlled trialSingle-blind fashionSubscale scoresBPRS total scorePsychiatric Rating ScaleDSM-III criteriaSubsequent treatmentRepeated-measures analysisNaltrexone augmentationNeuroleptic medicinesNeuroleptic regimenTransient exacerbationPlacebo armNeuroleptic treatmentClinical benefitRepeated-measures ANOVANaltrexone
1996
Nimodipine reduction of naltrexone-precipitated locus coeruleus activation and abstinence behavior in morphine-dependent rats
Krystal J, Compere S, Nestler E, Rasmussen K. Nimodipine reduction of naltrexone-precipitated locus coeruleus activation and abstinence behavior in morphine-dependent rats. Physiology & Behavior 1996, 59: 863-866. PMID: 8778878, DOI: 10.1016/0031-9384(95)02206-6.Peer-Reviewed Original ResearchConceptsL-type calcium channel antagonistLocus coeruleus neuronsMorphine-dependent ratsOpiate-dependent ratsCalcium channel antagonistsSingle-unit recordingsLocus coeruleus activationNimodipine effectCoeruleus neuronsNoradrenergic mechanismsOpiate withdrawalLocus coeruleusChannel antagonistsAnesthetized animalsNimodipineAbstinence behaviorTime courseRatsWithdrawal behaviorActivationNaltrexoneCoeruleus