Ismene Petrakis, MD
Professor of PsychiatryCards
Appointments
Additional Titles
Chief of Psychiatry, VA Connecticut Healthcare System
Contact Info
Psychiatry
950 Campbell Ave, 116-A
West Haven, CT 06516
United States
Appointments
Additional Titles
Chief of Psychiatry, VA Connecticut Healthcare System
Contact Info
Psychiatry
950 Campbell Ave, 116-A
West Haven, CT 06516
United States
Appointments
Additional Titles
Chief of Psychiatry, VA Connecticut Healthcare System
Contact Info
Psychiatry
950 Campbell Ave, 116-A
West Haven, CT 06516
United States
About
Titles
Professor of Psychiatry
Chief of Psychiatry, VA Connecticut Healthcare System
Biography
Dr. Petrakis is a Professor of Psychiatry at Yale University School of Medicine and the Director of the Mental Health Service Line at VA Connecticut Healthcare System (VACHS) since July 2010. Dr. Petrakis completed residency training at Yale School of Medicine and then a NIDA-funded addiction psychiatry clinical/research fellowship. She joined the faculty in 1992. Prior to July 2010, she was the Director of the Substance Abuse Treatment Program of the VACHS since 1996.
Dr. Petrakis is also the Director of the Addiction Psychiatry Residency at Yale, an ACGME-accredited program and the PI of both an NIAAA-funded and a NIDA-funded training grant (T32).
Her research interests are predominately two-fold: (1) finding appropriate
treatments for dually diagnosed individuals and (2) understanding the
neurobiological mechanisms underlying alcohol dependence. She has received funding from the Department
of Defense, NIH-NIAAA, the VA, NARSAD and the Stanley Foundation.
Appointments
Psychiatry
ProfessorPrimary
Other Departments & Organizations
- Addiction Medicine Fellowship Program
- Adult Psychiatry
- ADVANCE Study
- Alcoholism Treatment Center
- Center for the Translational Neuroscience of Alcohol
- Connecticut Mental Health Center
- Division of Addictions
- Division of Mental Health Services
- Neuroscience Research Training Program (NRTP)
- Psychiatry
- Psychotherapy Development Center
- Yale Ventures
- Yale-Drug use, Addiction, and HIV prevention Research Scholars (DAHRS)
Education & Training
- Fellow, Addiction
- Yale University School of Medicine (1992)
- Residency
- Yale University School of Medicine (1991)
- MD
- University of Pittsburgh (1987)
Research
Overview
1. Finding effective pharmacotherapies for individuals with alcohol dependence and comorbid psychiatric disorders. Although there is a large body of literature evaluating medications for the treatment of alcoholism and other substance use disorders, there are no established pharmacotherapies for individuals with comorbid psychiatric illnesses. Nevertheless, patients with substance dependence and comorbid mental disorders constitute the majority of patients in clinical settings, and the presence of comorbid mental disorders confers a poorer prognosis. Further, individuals with comorbid mental diseases have been systematically excluded from most efficacy studies of potential pharmacotherapies and more research is needed in this patient population. In fact, there is some evidence that patients with comorbid disorders may be less likely to get the treatment they need, particularly in mental health clinics. This research attempts to answer clinically relevant questions about efficacy, effectiveness and pharmacologic use in dually diagnosed individuals in order to better inform the development of treatments. This work has included a utilization studies about the use of naltrexone in alcohol dependent veterans; effectiveness studies such as a large effectiveness study with 254 veterans across 3 VA sites evaluating the use of naltrexone and disulfiram alone and in combination in a “real world” clinical setting. The results suggested that medications to treat alcoholism are safe and effective in these patients and more effective than no medication. Interestingly, there was no advantage to combination treatment. Individuals with Post Traumatic Stress Disorder (PTSD) and those with psychosis did particularly well with medications to treat alcoholism.
In one of the first controlled studies to evaluate naltrexone for individuals with alcohol dependence and serious psychiatric disorder, patients with schizophrenia and alcohol dependence were randomized to naltrexone or placebo for a 12-week clinical trial. Naltrexone-treated patients had better alcohol related outcomes than placebo-treated patients. However, since naltrexone did not improve symptoms of psychosis or cognitive effects, further studies focused on treatments that might effectively treat symptoms of both disorders. Using administrative data, one study found that atypical neuroleptics are associated with no better outcomes than typical neuroleptics for substance misuse in schizophrenic patients. In a “proof of concept” treatment study evaluating a glutamatergic agent, a Stanley foundation-funded clinical trial was conducted using glycine as a treatment of both alcohol misuse and symptoms of schizophrenia. Preliminary results support previous research that glycine is effective for the negative symptoms of schizophrenia, but not alcohol consumption. It should be noted that the final data analysis is not yet complete. More recently and after the FDA approved acamprosate for the treatment of alcoholism, a study was funded and is ongoing evaluating acamprosate’s efficacy in patients with comorbid schizophrenia.
Individuals with PTSD have some of the highest rates of comorbid alcohol dependence and this is an important clinical issue,particularly at the VA. A recently completed study was conducted comparing 2antidepressants (a noradrenergic agent versus a serotonergic agent) in treating symptoms of both PTSD and alcoholism. Preliminary results suggest there were no differences between the groups; the equivalent efficacy of a noradrenergic agent with the more standard serotonergic agent is a promising finding. Building on these results I have obtained grant funding from the Department of Defense to evaluate a novel noradrenergic agent in the treatment of PTSD and comorbid alcohol dependence. The study was funded in September of ’08.
2. Evaluating the underlying neurobiology of these disorders and the behaviors that go with them, including craving,self-administration and a familial vulnerability. Advances in the understanding of alcohol’s effects on the brain and the associated behavioral effects have contributed to our knowledge of alcohol abuse and dependence and have led the way to the development of new treatments. Alcohol is now known to have multiple specific actions in the brain. Alcohol’s acute and chronic effects on specific targets in the brain may in part explain ethanol reward, dependence and the vulnerability to alcoholism.
Dr. Petrakis' research has focused on the serotonergic and glutamatergic systems and how these neurotransmitters affect craving, self-administration of alcohol and the vulnerability to develop alcoholism. Contrary to what might be expected from preclinical studies, 2 NIAAA-funded studies found there was no significant correlation of serotonin function with the magnitude of cue-induced craving and that cue included craving and alcohol self-administration were not dependent on ongoing synthesis of serotonin.
Much evidence supports the role of the n-methyl-d-aspartate (NMDA) glutamate receptor in the pathophysiology of alcoholism. Another NIAAA-funded study evaluated whether healthy individuals at increased familial risk to develop alcohol dependence exhibit alterations in NMDA receptor function. This objective was evaluated by comparing the dose-related effects of the NMDA receptor antagonist, ketamine, in healthy individuals with a strong family history of ethanol dependence compared to healthy individuals without a family history. Interestingly, individuals with a family history were found to be less sensitive to the subjective effects of ketamine than those without a family history. These results are being followed up and in order to both replicate the findings and to determine whether certain genotypes predict outcome in a second-round of NIAAA funded studies. In a collaboration with Dr. Albert Perrino of the Department of Anesthesiology we are also evaluating whether altered pain sensitivity is also a marker for the vulnerability to develop alcoholism.
Two new areas of study include the examination of gamma-aminobutyric acid (GABA) mechanisms underlying both the subjective effects of alcohol and the vulnerability to develop alcoholism using a barbiturate probe, and the role of nicotinic acetylcholine receptors in alcoholism. For the latter, a newly funded NIAAA grant (Sept 08) is examining the potential for the nicotinic receptor antagonist mecamylamine to attenuate alcohol use in alcohol dependent individuals.
- The Use of Prazosin for Treatment of Patients with Alcohol Dependence (AD) and Post-Traumatic Stress Disorder (PTSD)
- Treatment with Mecamylamine in Smoking and Non-Smoking Alcohol Dependent Patients
- Acamprosate for patients with Schizophrenia and Alcohol Dependence
- IV Alcohol Administration using a BrAC Method in Healthy Subjects with and without a Family History
- NMDA Dysregulation in Individuals with Family Vulnerability to Alcoholism
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
John Krystal, MD
Deepak Cyril Dsouza, MBBS, MD
Louis Trevisan, MD
Mehmet Sofuoglu, MD, PhD
Peter Jongho Na, MD, MPH
Elizabeth Ralevski, PhD
Alcoholism
Substance-Related Disorders
Veterans
Comorbidity
Diagnosis, Dual (Psychiatry)
Psychiatry
Publications
2024
Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo‐controlled crossover laboratory study
Petrakis I, Nolen T, Vandergrift N, Hirsch S, Krystal J, De Vivo M, Sabados J, Pisani E, Newcomb J, Kosten T. Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo‐controlled crossover laboratory study. American Journal On Addictions 2024 PMID: 39152094, DOI: 10.1111/ajad.13637.Peer-Reviewed Original ResearchConceptsPathophysiology of posttraumatic stress disorderAlcohol use disorderSubjective effects of alcoholEffects of alcoholUse disorderComorbid alcohol use disorderAlcohol cue reactivityPosttraumatic stress disorderCrossover laboratory studyCue reactivityAlcohol cravingNoradrenergic dysregulationStress disorderBlood pressureSubjective effectsEthanol administrationClinically significant adverse effectsPharmacotherapeutic approachesTest daysReceptor agonistsPotential treatmentDouble-blind fashionCravingDrinking alcoholDisordersThe Impact of High-Potency Synthetic Opioids on Pharmacotherapies for Opioid Use Disorder: A Scoping Review
Jegede O, De Aquino J, Hsaio C, Caldwell E, Funaro M, Petrakis I, Muvvala S. The Impact of High-Potency Synthetic Opioids on Pharmacotherapies for Opioid Use Disorder: A Scoping Review. Journal Of Addiction Medicine 2024 DOI: 10.1097/adm.0000000000001356.Peer-Reviewed Original ResearchAltmetricConceptsNonmedical opioid useOpioid use disorderOpioid useWithdrawal symptomsTreatment outcomesSymptoms prior to treatmentUse disorderRisk of precipitated withdrawalLow-dose buprenorphineSynthetic opioidsPotency synthetic opioidsConclusions Current evidencePrecipitated withdrawalRisk of overdoseDosing strategiesPharmacological interactionsClinical significanceDecreased riskWeb of ScienceOpioidInclusion criteriaCurrent evidenceClinical implicationsMOUDPainThe combination of donepezil and cognitive training for improving treatment outcomes for alcohol use disorder: Design of a randomized controlled trial
Yoon G, Sofuoglu M, Petrakis I, Pittman B, Bell M. The combination of donepezil and cognitive training for improving treatment outcomes for alcohol use disorder: Design of a randomized controlled trial. Contemporary Clinical Trials 2024, 145: 107657. PMID: 39111388, DOI: 10.1016/j.cct.2024.107657.Peer-Reviewed Original ResearchConceptsCognitive remediation therapyAlcohol use disorderAlcohol use disorder treatment outcomesNeurocognitive functionCombination of donepezilRemediation therapyUse disorderTreatment outcomesDevelopment of alcohol use disordersReduce heavy drinking daysHeavy drinking daysGlobal neurocognitive functioningImprove neurocognitive functionEnhanced neurocognitive functionImprove cognitive functionRandomized controlled trialsReduce alcohol consumptionNeurobiological evidenceDrinking daysNeurocognitive function scoresCognitive trainingVA Connecticut Healthcare SystemCognitive functionImprove treatment outcomesCognitive impairmentMedial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression
Swanberg K, Prinsen H, Averill C, Campos L, Kurada A, Krystal J, Petrakis I, Averill L, Rothman D, Abdallah C, Juchem C. Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression. NMR In Biomedicine 2024, e5220. PMID: 39054694, DOI: 10.1002/nbm.5220.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMedial prefrontal cortexStress disorderPosttraumatic stress disorder patientsPosttraumatic stress disorder diagnosisChronic psychiatric conditionImpact of psychiatric comorbiditiesComorbid MDDPrefrontal cortexDepressive disorderTraumatic stressorsPsychiatric conditionsMDDPsychiatric comorbiditiesNeurotransmitter abnormalitiesConcentrations of glutamateMetabolite abnormalitiesHealthy controlsDisordersPattern of abnormalitiesParticipantsGlutamateIn vivo protonMetabolic abnormalitiesDepressionA Systematic Review Evaluating PTSD Treatment Effects on Intermediate Phenotypes of PTSD
Palmisano A, Meshberg-Cohen S, Petrakis I, Sofuoglu M. A Systematic Review Evaluating PTSD Treatment Effects on Intermediate Phenotypes of PTSD. Psychological Trauma Theory Research Practice And Policy 2024, 16: 768-783. PMID: 36595460, DOI: 10.1037/tra0001410.Peer-Reviewed Original ResearchCitationsAltmetricConceptsPosttraumatic stress disorderBehavioral treatment outcomesEvidence-based treatmentsCognitive controlThreat processingBody of researchPTSD outcomesPTSD treatmentPaucity of researchStress disorderPreliminary supportIntermediate phenotypesTreatment dropoutMethodological limitationsStudy limitationsTreatment effectsCurrent researchTreatment approachesStrong conclusionsNovel treatment approachesEmpirical studyTreatment outcomesTreatment efficacyResearchMemoryHealth correlates of experiential and behavioral avoidance among trauma-exposed veterans
Schwartz E, Palmisano A, Petrakis I, Pietrzak R, Sofuoglu M. Health correlates of experiential and behavioral avoidance among trauma-exposed veterans. Journal Of Psychiatric Research 2024, 176: 213-217. PMID: 38878649, DOI: 10.1016/j.jpsychires.2024.06.014.Peer-Reviewed Original ResearchConceptsTrauma-exposed veteransExperiential avoidanceBehavioral avoidanceAnxiety symptomsDepressive symptomsMental health outcomesCognitive dysfunctionPhysical healthPhysical health outcomesHealth outcomesQuality of lifeHealth-related dysfunctionTrauma historyPsychosocial functioningCognitive functionAvoidance behaviorOutcome measuresHealth-related quality of lifeTreatment targetDistressExploratory analysisVeteransHealth-related qualityAvoidanceAnxietyAlcohol Use Disorder and Chronic Pain: An Overlooked Epidemic
De Aquino J, Sloan M, Nunes J, Costa G, Katz J, de Oliveira D, Ra J, Tang V, Petrakis I. Alcohol Use Disorder and Chronic Pain: An Overlooked Epidemic. American Journal Of Psychiatry 2024, 181: 391-402. PMID: 38706339, DOI: 10.1176/appi.ajp.20230886.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsAlcohol use disorderChronic painAUD studiesChronic pain disordersChronic pain outcomesRisk of relapseAlcohol withdrawal syndromeAssessment of painHigher levels of alcohol consumptionLevels of alcohol consumptionWithdrawal syndromePain disordersPain outcomesAcute toleranceNeurobiological changesClinical significanceUse disorderPainClinical relevanceSelf-reportAlcohol intoxicationAlcohol consumptionGeneral populationMedical conditionsNarrative reviewCognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine
Petrakis I, Meshberg‐Cohen S, Nich C, Kelly M, Claudio T, Jane J, Pisani E, Ralevski E. Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine. American Journal On Addictions 2024 PMID: 38624259, DOI: 10.1111/ajad.13557.Peer-Reviewed Original ResearchAltmetricConceptsCognitive processing therapyIndividual drug counselingPosttraumatic stress disorderOpioid use disorderSubstance use disordersDrug counselingProcessing therapyPTSD symptomsUse disorderCognitive processing therapy groupEvidence-based trauma-focused psychotherapiesSelf-reported PTSD symptomsPosttraumatic stress disorder symptomsPosttraumatic stress disorder treatmentRemission of PTSD symptomsPosttraumatic Stress Disorder ChecklistComorbid opioid use disorderTrauma-focused psychotherapyTrauma-focused treatmentRates of comorbidityTreatment group differencesPCL-5Stress disorderGroup differencesRandomized clinical trialsProblem Opioid Use Among US Military Veterans: Prevalence, Correlates, and Psychiatric Characteristics
Na P, Petrakis I, Krystal J, Pietrzak R. Problem Opioid Use Among US Military Veterans: Prevalence, Correlates, and Psychiatric Characteristics. Journal Of Addiction Medicine 2024, 18: 313-318. PMID: 38498625, PMCID: PMC11150085, DOI: 10.1097/adm.0000000000001286.Peer-Reviewed Original ResearchCitationsConceptsInstrumental activities of daily livingInstrumental activities of daily living disabilityLifetime suicide attemptsProblem opioid useUS military veteransUS veteransPsychiatric characteristicsSuicide attemptsMilitary veteransAssociated with black race/ethnicityActivities of daily livingNational Health and ResilienceLifetime alcohol use disorderMental health morbidityPosttraumatic stress disorderMental health disordersAlcohol use disorderNon-Hispanic race/ethnicityMultivariate logistic regression modelNationally representative sampleOpioid useLogistic regression modelsInstrumental activitiesHealth morbidityDaily livingThe Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.
Schnurr P, Hamblen J, Wolf J, Coller R, Collie C, Fuller M, Holtzheimer P, Kelly U, Lang A, McGraw K, Morganstein J, Norman S, Papke K, Petrakis I, Riggs D, Sall J, Shiner B, Wiechers I, Kelber M. The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline. Annals Of Internal Medicine 2024, 177: 363-374. PMID: 38408360, DOI: 10.7326/m23-2757.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsClinical practice guidelinesU.S. Department of Veterans AffairsDepartment of Veterans AffairsVeterans AffairsPosttraumatic stress disorderManagement of posttraumatic stress disorderAcute stress disorderExternal group of expertsPractice guidelinesDefense Clinical Practice GuidelinesStress disorderPatient-centered careIndividual health outcomesRevised CPGDepartment of Defense Clinical Practice GuidelinesVideo teleconferencingStrength of evidenceQuality of lifeCo-occurring conditionsHealth outcomesPatient perspectiveEvidence-basedPosttraumatic stress disorder treatmentSystematic searchCognitive processing therapy
Clinical Trials
Current Trials
Alcohol Interaction Study
HIC ID2000030342RolePrincipal InvestigatorPrimary Completion Date01/31/2023Recruiting ParticipantsGenderBothAge21 years - 65 yearsBehavioral and Neurochemical Mechanisms Underlying Stress-Precipitated Drinking
HIC ID2000021685RoleSub InvestigatorPrimary Completion Date09/30/2022Recruiting ParticipantsGenderBothAge21 years - 55 years
Links & Media
News
- August 15, 2024Source: Journal of Addiction Medicine
The Impact of High-Potency Synthetic Opioids on Pharmacotherapies for Opioid Use Disorder: A Scoping Review
- May 06, 2024Source: The American Journal of Psychiatry
Alcohol Use Disorder and Chronic Pain: An Overlooked Epidemic
- September 22, 2023Source: Psychological Medicine
In Study of Veterans, Positive Personality Traits Moderate Persistent High Alcohol Consumption
- May 12, 2023Source: Academic Medicine
Academic Medical Centers and the U.S. Department of Veterans Affairs: A 75-Year Partnership Influences Medical Education, Scientific Discovery, and Clinical Care
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Contacts
Psychiatry
950 Campbell Ave, 116-A
West Haven, CT 06516
United States