2025
Long-Term Safety and Efficacy of Esmethadone in Patients With Major Depressive Disorder: Findings From a 12-Month Open-Label Study.
Fava M, Pani L, De Martin S, Cutler A, Gorodetzky C, Vocci F, Sapienza F, Kosten T, Kröger C, Champasa P, Guidetti C, Comai S, Mattarei A, Folli F, Bushnell D, Traversa S, Inturrisi C, Manfredi P, Pappagallo M. Long-Term Safety and Efficacy of Esmethadone in Patients With Major Depressive Disorder: Findings From a 12-Month Open-Label Study. The Journal Of Clinical Psychiatry 2025, 86 PMID: 39999772, DOI: 10.4088/jcp.24m15438.Peer-Reviewed Original ResearchConceptsDepressive disorderColumbia-Suicide Severity Rating ScaleOpen-label studyDSM-5</i> criteriaFull analysis setMajor depressive disorderMeasures of depressionSeverity Rating ScaleSexual adverse eventsAntidepressant efficacyTreatment-emergent adverse eventsPostbaseline efficacy assessmentAdverse eventsSuicide attemptsUncompetitive antagonistCognitive functionSafety populationEfficacy assessmentRating ScaleEfficacy measuresMDDDouble-blind studyEmergent adverse eventsLong-term treatmentTreatment-related treatment-emergent adverse events
2023
Efficacy and safety of ketamine-assisted electroconvulsive therapy in major depressive episode: a systematic review and network meta-analysis
Rhee T, Shim S, Popp J, Trikalinos T, Rosenheck R, Kellner C, Seiner S, Espinoza R, Forester B, McIntyre R. Efficacy and safety of ketamine-assisted electroconvulsive therapy in major depressive episode: a systematic review and network meta-analysis. Molecular Psychiatry 2023, 29: 750-759. PMID: 38123725, DOI: 10.1038/s41380-023-02366-8.Peer-Reviewed Original ResearchMajor depressive episodeStandardized mean differenceElectroconvulsive therapyAnesthetic agentsDepressive symptomsDepressive episodeRelative riskDiagnosis of MDESystematic reviewKetamine-treated patientsSafety of ketamineSerious adverse eventsResultsTwenty-two studiesMethodsPubMed/MEDLINEImportant clinical considerationsRandom-effects modelCognitive performanceAdverse eventsAntidepressant efficacyECT useTrials RegistryClinical efficacyCochrane LibraryWorse outcomesPatient profilesPathophysiology of nAChRs: Limbic circuits and related disorders
Mineur Y, Soares A, Etherington I, Abdulla Z, Picciotto M. Pathophysiology of nAChRs: Limbic circuits and related disorders. Pharmacological Research 2023, 191: 106745. PMID: 37011774, DOI: 10.1016/j.phrs.2023.106745.Peer-Reviewed Original ResearchConceptsDepressive disorderMedication developmentLimbic system areasPreclinical pharmacological studiesHuman epidemiological studiesHuman affective disordersNicotinic acetylcholine receptorsAntidepressant efficacyClinical evidenceLimbic circuitsNicotine intakePreclinical modelsSpecific nAChRsEpidemiological studiesCurrent therapeuticsAffective disordersAcetylcholine receptorsRelated disordersPharmacological studiesStress disorderDisordersEtiology of anxietyNAChRsRelevant targetsEfficacy
2021
Parsing the antidepressant effects of non-invasive brain stimulation and pharmacotherapy: A symptom clustering approach on ELECT-TDCS
Goerigk S, Padberg F, Chekroud A, Kambeitz J, Bühner M, Brunoni A. Parsing the antidepressant effects of non-invasive brain stimulation and pharmacotherapy: A symptom clustering approach on ELECT-TDCS. Brain Stimulation 2021, 14: 906-912. PMID: 34048940, DOI: 10.1016/j.brs.2021.05.008.Peer-Reviewed Original ResearchConceptsTranscranial direct current stimulationNon-invasive brain stimulationDepressive symptomsBrain stimulationEfficacy of tDCSCore depressive symptomsLinear mixed regression modelsDepressive symptom clustersConsiderable inter-individual variabilityDirect current stimulationEscitalopram 20Antidepressant effectsAntidepressant efficacyInter-individual variabilityAtypical symptomsDepressed patientsMixed regression modelsInsomnia symptomsTDCS sessionsPharmacotherapyEscitalopramSymptomsPlaceboSymptom clustersCurrent stimulation
2020
Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants
Kadriu B, Greenwald M, Henter ID, Gilbert JR, Kraus C, Park LT, Zarate CA. Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants. The International Journal Of Neuropsychopharmacology 2020, 24: 8-21. PMID: 33252694, PMCID: PMC7816692, DOI: 10.1093/ijnp/pyaa087.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsKetamine researchSerotonergic psychedelicsAntidepressant effectsAntidepressant efficacyRapid-acting antidepressantsRapid acting antidepressantsGlutamatergic modulator ketamineCortical network activityDownstream pharmacological effectsActivity-dependent mannerAcute alterationsTherapeutic responseNeuroplastic effectsGlutamatergic pathwaysPharmacological effectsKetaminePsychoactive componentTherapeutic relevanceAntidepressantsDownstream mechanismsPsychoactive effectsMolecular effectsNetwork activityCommon mechanismEfficacyChapter 7 Neuroprotective roles of neurotrophic growth factors in mood disorders
Jiang C, Salton S. Chapter 7 Neuroprotective roles of neurotrophic growth factors in mood disorders. 2020, 145-172. DOI: 10.1016/b978-0-12-814037-6.00010-0.Peer-Reviewed Original ResearchBrain-derived neurotrophic factorNeurotrophic growth factorsMood disordersAntidepressant efficacyDepressive behaviorGrowth factorDepression-like behaviorAntidepressant actionAntidepressant responseDendritic lengthNeuroprotective roleSpine densityNeurotrophic factorNeurotrophin actionNeuronal cytoarchitectureAnimal modelsGene polymorphismsSynaptic plasticityProtein levelsDisordersReceptorsGenetic associationEfficacySpecific mechanismsCritical role
2019
Grape‐derived polyphenols produce antidepressant effects via VGF‐ and BDNF‐dependent mechanisms
Jiang C, Sakakibara E, Lin W, Wang J, Pasinetti GM, Salton SR. Grape‐derived polyphenols produce antidepressant effects via VGF‐ and BDNF‐dependent mechanisms. Annals Of The New York Academy Of Sciences 2019, 1455: 196-205. PMID: 31074515, PMCID: PMC6834858, DOI: 10.1111/nyas.14098.Peer-Reviewed Original ResearchConceptsDepression-like behaviorAntidepressant efficacyTLQP-62VGF-derived peptide TLQP-62Stress-induced depression-like behaviorsBDNF-dependent mechanismAntidepressant-like effectsChronic variable stressGrape-derived polyphenolsAntidepressant actionAntidepressant effectsBDNF expressionNaive miceDorsal hippocampusPolyphenol preparationsFloxed miceVGF expressionPrior knockdownEfficacyVGFMiceMolecular mechanismsRecent studiesVariable stressBDNFKetamine: A Paradigm Shift for Depression Research and Treatment
Krystal JH, Abdallah CG, Sanacora G, Charney DS, Duman RS. Ketamine: A Paradigm Shift for Depression Research and Treatment. Neuron 2019, 101: 774-778. PMID: 30844397, PMCID: PMC6560624, DOI: 10.1016/j.neuron.2019.02.005.Peer-Reviewed Original Research
2018
VGF and its C-terminal peptide TLQP-62 in ventromedial prefrontal cortex regulate depression-related behaviors and the response to ketamine
Jiang C, Lin WJ, Labonté B, Tamminga CA, Turecki G, Nestler EJ, Russo SJ, Salton SR. VGF and its C-terminal peptide TLQP-62 in ventromedial prefrontal cortex regulate depression-related behaviors and the response to ketamine. Neuropsychopharmacology 2018, 44: 971-981. PMID: 30504797, PMCID: PMC6462025, DOI: 10.1038/s41386-018-0277-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsBehavior, AnimalBrain-Derived Neurotrophic FactorDepressionDepressive Disorder, MajorDisease Models, AnimalDisease SusceptibilityFemaleHumansKetamineMaleMiceMice, 129 StrainMice, Inbred C57BLMice, TransgenicNerve Growth FactorsNeuropeptidesPeptidesPrefrontal CortexStress, PsychologicalConceptsChronic restraint stressMajor depressive disorderAntidepressant efficacyAntidepressant responseVentromedial prefrontal cortexPrefrontal cortexAntidepressant drug treatmentKetamine's antidepressant efficacyAntidepressant-like effectsDepression-related behaviorsBrodmann area 25Neuropeptide precursor VGFChannel-mediated Ca2Underlying molecular pathwaysTLQP-62Vgf knockdownVGF levelsBDNF expressionMDD patientsRestraint stressDepressive disorderFunctional deficitsDrug treatmentBehavioral deficitsNucleus accumbensRole of a VGF/BDNF/TrkB Autoregulatory Feedback Loop in Rapid-Acting Antidepressant Efficacy
Jiang C, Lin WJ, Salton SR. Role of a VGF/BDNF/TrkB Autoregulatory Feedback Loop in Rapid-Acting Antidepressant Efficacy. Journal Of Molecular Neuroscience 2018, 68: 504-509. PMID: 30022437, PMCID: PMC6338529, DOI: 10.1007/s12031-018-1124-0.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorRapid-acting antidepressantsTLQP-62Antidepressant efficacyReceptor activationN-methyl-D-aspartate receptorsParticular brain-derived neurotrophic factorIsoxazolepropionic acid receptor (AMPAR) activationBDNF/TrkBDepression-like behaviorRapid antidepressant actionsIntra-hippocampal administrationAMPA receptor activationExpression of VGFChemical antidepressantsAntidepressant actionBDNF expressionSustained efficacyNeurotrophic factorNeurotrophin familySwim testVoluntary exerciseMTOR pathwayMTOR activationAntidepressantsInteraction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice
Mineur YS, Cahuzac EL, Mose TN, Bentham MP, Plantenga ME, Thompson DC, Picciotto MR. Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice. Neuropsychopharmacology 2018, 43: 2118-2125. PMID: 29472646, PMCID: PMC6098039, DOI: 10.1038/s41386-018-0024-x.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAdrenergic alpha-AgonistsAlkaloidsAmygdalaAnimalsAnxietyAzocinesCholinesterase InhibitorsDepressionFemaleGene Knockdown TechniquesGuanfacineMaleMiceMice, Inbred C57BLNicotinic AgonistsNorepinephrineParasympathetic Nervous SystemQuinolizinesReceptors, Adrenergic, alpha-2Signal TransductionSympathetic Nervous SystemConceptsAntidepressant-like effectsNoradrenergic systemMale C57BL/6J miceDepression-related behaviorsDepression-like phenotypeNicotinic acetylcholine receptorsAntidepressant efficacyCholinergic interactionsNE terminalsC57BL/6J miceShRNA-mediated knockdownAgonist guanfacineAgonist cytisineClinical studiesSmoking relapseΑ2A receptorsAcute abstinenceBrain areasAcetylcholine receptorsAcetylcholineGuanfacineAmygdalaBehavioral effectsAnxiety disordersStress pathways
2017
VGF function in depression and antidepressant efficacy
Jiang C, Lin WJ, Sadahiro M, Labonté B, Menard C, Pfau ML, Tamminga CA, Turecki G, Nestler EJ, Russo SJ, Salton SR. VGF function in depression and antidepressant efficacy. Molecular Psychiatry 2017, 23: 1632-1642. PMID: 29158577, PMCID: PMC5962361, DOI: 10.1038/mp.2017.233.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntidepressive AgentsBrain-Derived Neurotrophic FactorDepressionDepressive DisorderDown-RegulationFemaleHippocampusHumansKetamineMaleMiceMice, Inbred C57BLMiddle AgedNerve Growth FactorsNeuronsNeuropeptidesNucleus AccumbensReceptors, AMPASex FactorsSignal TransductionStress, PsychologicalTOR Serine-Threonine KinasesUp-RegulationConceptsChronic social defeat stressDepression-like behaviorBrain-derived neurotrophic factorSocial defeat stressNucleus accumbensAntidepressant efficacyAntidepressant responseDefeat stressFloxed micePro-depressant effectsRapid antidepressant efficacyBDNF/TrkBIsoxazolepropionic acid (AMPA) receptorsWild-type miceDepressed human subjectsBDNF translationTLQP-62VGF levelsAAV-CreAntidepressant behaviorNeurotrophic factorSwim testDorsal hippocampusInhibitory interneuronsVGF expressionMetabotropic Glutamatergic Receptor 5 and Stress Disorders: Knowledge Gained From Receptor Imaging Studies
Esterlis I, Holmes SE, Sharma P, Krystal JH, DeLorenzo C. Metabotropic Glutamatergic Receptor 5 and Stress Disorders: Knowledge Gained From Receptor Imaging Studies. Biological Psychiatry 2017, 84: 95-105. PMID: 29100629, PMCID: PMC5858955, DOI: 10.1016/j.biopsych.2017.08.025.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPositron emission tomography studyEmission tomography studiesMGluR5 modulationAntidepressant responseStress disorderBipolar disorderStress-related psychiatric disordersTomography studyAntagonism of mGluR5Ketamine’s antidepressant responseSignificant side effectsPromising therapeutic targetReceptor imaging studiesPosttraumatic stress disorderMDD heterogeneityManic mood statesAntidepressant efficacyObsessive-compulsive disorderDepressive disorderSubtype 5Neurotransmitter systemsPsychiatric disordersReceptor 5Side effectsA Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Design Trial of Adjunctive Riluzole for Treatment-Resistant Major Depressive Disorder
Mathew SJ, Gueorguieva R, Brandt C, Fava M, Sanacora G. A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Design Trial of Adjunctive Riluzole for Treatment-Resistant Major Depressive Disorder. Neuropsychopharmacology 2017, 42: 2567-2574. PMID: 28553836, PMCID: PMC5686483, DOI: 10.1038/npp.2017.106.Peer-Reviewed Original ResearchConceptsMajor depressive disorderSecondary efficacy outcomesEfficacy outcomesNeuroprotective effectsDepressive disorderResponse rateTreatment-resistant major depressive disorderMontgomery-Åsberg Depression Rating ScaleClinical Global Impressions-SeverityCurrent major depressive episodeDose of riluzolePlacebo/placeboSafety of riluzoleFixed-dose trialTreatment-resistant depressionSide effect profileGlutamate-modulating agentsMajor depressive episodeDepression Rating ScaleLack of efficacyPatient-reported measuresAmyotrophic lateral sclerosisSequential parallel comparison designRiluzole effectsAntidepressant efficacyKetamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression
Esterlis I, DellaGioia N, Pietrzak RH, Matuskey D, Nabulsi N, Abdallah CG, Yang J, Pittenger C, Sanacora G, Krystal JH, Parsey RV, Carson RE, DeLorenzo C. Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression. Molecular Psychiatry 2017, 23: 824-832. PMID: 28397841, PMCID: PMC5636649, DOI: 10.1038/mp.2017.58.Peer-Reviewed Original ResearchConceptsMajor depressive disorderMGluR5 availabilityPositron emission tomographyKetamine administrationControl groupAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced reductionMetabotropic glutamatergic receptorsRapid antidepressant effectsGlutamate receptor antagonistsKetamine-induced changesEffects of ketaminePET imaging studiesMechanism of actionGlutamate surgeAntidepressant effectsAntidepressant efficacyAntidepressant responseGlutamatergic receptorsControl subjectsReceptor antagonistHealthy controlsDepressive disorderSustained decreaseAdministration of ketamine for unipolar and bipolar depression
Kraus C, Rabl U, Vanicek T, Carlberg L, Popovic A, Spies M, Bartova L, Gryglewski G, Papageorgiou K, Lanzenberger R, Willeit M, Winkler D, Rybakowski JK, Kasper S. Administration of ketamine for unipolar and bipolar depression. International Journal Of Psychiatry In Clinical Practice 2017, 21: 2-12. PMID: 28097909, DOI: 10.1080/13651501.2016.1254802.Peer-Reviewed Original ResearchConceptsBipolar depressionSide effectsResponse rateMost common side effectsLong-term side effectsHamilton Depression Rating ScaleAntidepressant response ratesNausea/vomitingOpen-label trialRapid antidepressant efficacyTreatment-resistant depressionAnti-suicidal effectsCommon side effectsEfficacious treatment optionPrimary outcome measureAdministration of ketamineDepression Rating ScaleNew administration routesWeb of ScienceKetamine efficacyResistant depressionAntidepressant efficacyRelapse rateAntidepressant responseSafety profile
2015
Differential Effects of an NR2B NAM and Ketamine on Synaptic Potentiation and Gamma Synchrony: Relevance to Rapid-Onset Antidepressant Efficacy
Nagy D, Stoiljkovic M, Menniti FS, Hajós M. Differential Effects of an NR2B NAM and Ketamine on Synaptic Potentiation and Gamma Synchrony: Relevance to Rapid-Onset Antidepressant Efficacy. Neuropsychopharmacology 2015, 41: 1486-1494. PMID: 26404843, PMCID: PMC4832008, DOI: 10.1038/npp.2015.298.Peer-Reviewed Original ResearchConceptsAuditory-evoked potentialsAntidepressant effectsSynaptic potentiationAntidepressant efficacyAuditory gatingRapid-onset antidepressant effectsEffects of ketaminePrimary auditory cortexReceptor channel blockerDifferent acute effectsNMDA receptor inhibitionNegative allosteric modulatorsPotential mechanistic underpinningsReceptor inhibitionSystemic administrationAcute effectsNeurophysiological biomarkersTranslatable biomarkersChannel blockersDrug eliminationAuditory cortexNeurophysiological parametersDrug AdministrationGamma band powerKetamineAntidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice
Mineur YS, Bentham MP, Zhou WL, Plantenga ME, McKee SA, Picciotto MR. Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice. Psychopharmacology 2015, 232: 3539-3549. PMID: 26146014, PMCID: PMC4561580, DOI: 10.1007/s00213-015-4001-3.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsPaired-pulse ratioC-Fos immunoreactivityPrefrontal cortexSwim testBrain areasRobust antidepressant-like effectsBrain regionsSex differencesMale C57BL/6J miceDepression-like behaviorEffects of guanfacineAcetylcholinesterase inhibitor physostigmineLight/dark boxBaseline sex differencesC-fos expressionDepression-like stateCritical brain regionsDifferent brain areasSex-specific changesAntidepressant efficacyCholinergic controlInhibitor physostigmineC57BL/6J miceAgonist guanfacine
2014
Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine
Mineur YS, Einstein EB, Bentham MP, Wigestrand MB, Blakeman S, Newbold SA, Picciotto MR. Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine. Neuropsychopharmacology 2014, 40: 938-946. PMID: 25288485, PMCID: PMC4330507, DOI: 10.1038/npp.2014.269.Peer-Reviewed Original ResearchMeSH Keywords8-Hydroxy-2-(di-n-propylamino)tetralinAlkaloidsAnimalsAntidepressive AgentsAzocinesDisease Models, AnimalDrug SynergismFluoxetineGene Expression RegulationHEK293 CellsHindlimb SuspensionHippocampusHumansInterpersonal RelationsMaleMiceMice, Inbred C57BLMotor ActivityQuinolizinesReceptor, Serotonin, 5-HT1ASelective Serotonin Reuptake InhibitorsSerotonin Receptor AgonistsStress, PsychologicalConceptsAntidepressant-like effectsSelective serotonin reuptake inhibitorsDorsal rapheCholinergic systemAgonist cytisineNicotinic acetylcholine receptor blockersEffects of cytisineTreatment-resistant patientsSerotonin reuptake inhibitorsAcetylcholine receptor blockerSSRI fluoxetineReceptor blockersAntidepressant efficacyReuptake inhibitorsSerotonin depletionCholinergic drugsMood disordersSerotonin receptorsMouse modelPharmacological approachesHippocampusReceptorsCytisineRapheMolecular mechanisms
2012
Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Antidepressant Efficacy of Ketamine in Depressed Patients
Laje G, Lally N, Mathews D, Brutsche N, Chemerinski A, Akula N, Kelmendi B, Simen A, McMahon FJ, Sanacora G, Zarate C. Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Antidepressant Efficacy of Ketamine in Depressed Patients. Biological Psychiatry 2012, 72: e27-e28. PMID: 22771240, PMCID: PMC3786174, DOI: 10.1016/j.biopsych.2012.05.031.Peer-Reviewed Original Research
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