Medscape InDiscussion: Major Depressive Disorder

Drs Madhukar Trivedi and Leanne M. Williams discuss defining subtypes and biotypes for depression to tailor more personalized treatments of major depressive disorder. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984466). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Depression https://emedicine.medscape.com/article/286759-overview Defining Biotypes for Depression and Anxiety Based on Large-scale Circuit Dysfunction: A Theoretical Review of the Evidence and Future Directions for Clinical Translation https://pubmed.ncbi.nlm.nih.gov/27653321/ Depression From a Precision Mental Health Perspective: Utilizing Personalized Conceptualizations to Guide Personalized Treatments https://pubmed.ncbi.nlm.nih.gov/34045980/ Acute and Longer-term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report https://pubmed.ncbi.nlm.nih.gov/17074942/ Depression Is the Leading Cause of Disability Around the World https://pubmed.ncbi.nlm.nih.gov/28418490/ Mapping Neural Circuit Biotypes to Symptoms and Behavioral Dimensions of Depression and Anxiety https://pubmed.ncbi.nlm.nih.gov/34482948/ Precision Psychiatry: A Neural Circuit Taxonomy for Depression and Anxiety https://pubmed.ncbi.nlm.nih.gov/27150382/ Childhood Trauma Predicts Antidepressant Response in Adults With Major Depression: Data From the Randomized International Study to Predict Optimized Treatment for Depression https://pubmed.ncbi.nlm.nih.gov/27138798/ Effect of Antidepressant Treatment on Cognitive Impairments Associated With Depression: A Randomised Longitudinal Study https://pubmed.ncbi.nlm.nih.gov/26995298/ Neuromodulation Surgery for Psychiatric Disorders https://emedicine.medscape.com/article/1343677-overview#a10 Use of Transcranial Magnetic Stimulation for Depression https://pubmed.ncbi.nlm.nih.gov/31355095/ Understanding Emotions: Origins and Roles of the Amygdala https://pubmed.ncbi.nlm.nih.gov/34072960/ Digital Therapeutics for Mental Health: Is Attrition the Achilles Heel? https://pubmed.ncbi.nlm.nih.gov/35982936/

Drs Madhukar H. Trivedi and Christoph U. Correll discuss the predictors of suicidal ideation, attempt, and death as well as how to address the topic of suicidality with patients and their loved ones. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984464). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Depression https://emedicine.medscape.com/article/286759-overview Prevalence of Suicidality in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Comparative Studies https://pubmed.ncbi.nlm.nih.gov/34603096/ Twelve-Month Prevalence of and Risk Factors for Suicide Attempts in the World Health Organization World Mental Health Surveys https://pubmed.ncbi.nlm.nih.gov/20816034/ Persistent Depressive Disorder https://www.ncbi.nlm.nih.gov/books/NBK541052/ Risk and Protective Factors for Suicide and Suicidal Behavior https://www.div12.org/wp-content/uploads/2012/10/Suicide-Risk-Factors-with-Graphics-Div12.pdf Prevention of Suicide by Clozapine in Mental Disorders: Systematic Review https://pubmed.ncbi.nlm.nih.gov/36640481/ Lithium Suicide Prevention: A Brief Review and Reminder https://pubmed.ncbi.nlm.nih.gov/30834169/ Trauma-Focused Psychotherapies for Post-Traumatic Stress Disorder: A Systematic Review and Network Meta-analysis https://pubmed.ncbi.nlm.nih.gov/34473342/ Intranasal Esketamine and Current Suicidal Ideation With Intent in Major Depression Disorder: Beat the Clock, Save a Life, Start a Strategy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203410/ Dextromethorphan/Bupropion (Rx) https://reference.medscape.com/drug/auvelity-dextromethorphan-bupropion-4000211 Status Update on the Sheehan-Suicidality Tracking Scale (S-STS) 2014 https://pubmed.ncbi.nlm.nih.gov/25520892/ Psychometric Properties of the Beck Depression Inventory-II: A Comprehensive Review https://pubmed.ncbi.nlm.nih.gov/24402217/ The 9-Item Concise Health Risk Tracking – Self-Report (CHRT-SR9) Measure of Suicidal Risk: Performance in Adult Primary Care Patients https://pubmed.ncbi.nlm.nih.gov/36865066/ Maximizing the Adequacy of Medication Treatment in Controlled Trials and Clinical Practice: STAR(*)D Measurement-Based Care https://pubmed.ncbi.nlm.nih.gov/17406651/ Psychometrics of the Self-Report Concise Associated Symptoms Tracking Scale (CAST-SR): Results From the STRIDE (CTN-0037) Study https://pubmed.ncbi.nlm.nih.gov/29325238/ Mechanisms of Action and Clinical Efficacy of NMDA Receptor Modulators in Mood Disorders https://pubmed.ncbi.nlm.nih.gov/28711661/ Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics https://pubmed.ncbi.nlm.nih.gov/30262987/ Zuranolone in Major Depressive Disorder: Results From MOUNTAIN-A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial https://pubmed.ncbi.nlm.nih.gov/36811520/ GABA Receptor Positive Allosteric Modulators https://www.ncbi.nlm.nih.gov/books/NBK554443/# Conjoint Therapy https://dictionary.apa.org/conjoint-therapy

Drs Madhukar Trivedi and Jeffrey Strawn discuss the impact of socioeconomic factors on outcomes of treatments in patients with major depressive disorder, including factors such as unemployment, race, sex, and age. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984460). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Depression https://emedicine.medscape.com/article/286759-overview Center for Clinical and Translational Science and Training (CCTST) https://www.cctst.org/ Socioeconomic Predictors of Treatment Outcomes Among Adults With Major Depressive Disorder https://pubmed.ncbi.nlm.nih.gov/35354325/ Cortisol and Major Depressive Disorder-Translating Findings From Humans to Animal Models and Back https://pubmed.ncbi.nlm.nih.gov/32038323/ Bayesian Hierarchical Models https://pubmed.ncbi.nlm.nih.gov/30535206/ The Impact of Age on Antidepressant Response: A Mega-Analysis of Individuals With Major Depressive Disorder https://pubmed.ncbi.nlm.nih.gov/36774767/ The Effectiveness of Individual Interpersonal Psychotherapy as a Treatment for Major Depressive Disorder in Adult Outpatients: A Systematic Review https://pubmed.ncbi.nlm.nih.gov/23312024/ Cognitive Behavioral Therapy for Depression https://emedicine.medscape.com/article/2094696-overview Depression and Psychodynamic Psychotherapy https://pubmed.ncbi.nlm.nih.gov/28614491/ Selective Serotonin Reuptake Inhibitors https://www.ncbi.nlm.nih.gov/books/NBK554406/ Cytochrome p450 Structure, Function and Clinical Significance: A Review https://pubmed.ncbi.nlm.nih.gov/28124606/  Optimizing Drug Selection in Psychopharmacology Based on 40 Significant CYP2C19- and CYP2D6-Biased Adverse Drug Reactions of Selective Serotonin Reuptake Inhibitors https://pubmed.ncbi.nlm.nih.gov/31616600/

Drs Madhukar Trivedi and Anita Clayton discuss how to approach patients with sexual dysfunction who are being treated for major depressive disorder. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984459). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Depression https://emedicine.medscape.com/article/286759-overview Treatment-Emergent Sexual Dysfunction Related to Antidepressants: A Meta-Analysis https://pubmed.ncbi.nlm.nih.gov/19440080/ Citizen Petition: Sexual Side Effects of SSRIs and SNRIs https://pubmed.ncbi.nlm.nih.gov/29733031/ Association of Major Depression With Sexual Dysfunction in Men https://pubmed.ncbi.nlm.nih.gov/23645187/ The Changes in Sexual Functioning Questionnaire (CSFQ): Development, Reliability, and Validity https://pubmed.ncbi.nlm.nih.gov/9493486/ Structured Review of the Use of the Arizona Sexual Experiences Scale in Clinical Settings https://pubmed.ncbi.nlm.nih.gov/32236977/ Hypoactive Sexual Desire Disorder: A Review of Epidemiology, Biopsychology, Diagnosis, and Treatment https://pubmed.ncbi.nlm.nih.gov/27872021/ Erectile Dysfunction https://pubmed.ncbi.nlm.nih.gov/31030826/ Sexual Dysfunction With Major Depressive Disorder and Antidepressant Treatments: Impact, Assessment, and Management https://pubmed.ncbi.nlm.nih.gov/35255754/ Overview of the Rapid Antidepressant Effects Observed in the Zuranolone Clinical Development Program https://journals.lww.com/greenjournal/Abstract/2022/05001/Overview_of_the_Rapid_Antidepressant_Effects.161.aspx Flibanserin prescribing information https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022526lbl.pdf

Drs Madhukar Trivedi and Lorenzo Norris address the issues of race, equity in care, and the importance of cultural competence when treating patients with major depressive disorder. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984455). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Depression https://emedicine.medscape.com/article/286759-overview Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) https://www.psychiatry.org/psychiatrists/practice/dsm The Cultural Formulation Interview: Building the Case for Cultural Competence in Clinical Care https://pubmed.ncbi.nlm.nih.gov/36722093/ Shared Decision Making https://www.medscape.org/shareddecisionmaking Promoting Collaborative Psychiatric Care Decision-Making in Community Mental Health Centers: Insights From a Patient-Centered Comparative Effectiveness Trial https://pubmed.ncbi.nlm.nih.gov/33119363/ Structured Clinical Interview for the DSM https://www.appi.org/products/structured-clinical-interview-for-dsm-5-scid-5 Psychometric Properties of Structured Clinical Interview for DSM-5 Disorders-Clinician Version (SCID-5-CV) https://pubmed.ncbi.nlm.nih.gov/33729681/ The Patient Health Questionnaire-2: Validity of a Two-Item Depression Screener https://pubmed.ncbi.nlm.nih.gov/14583691/ The PHQ-9: Validity of a Brief Depression Severity Measure https://pubmed.ncbi.nlm.nih.gov/11556941/

Drs Madhukar Trivedi and Manish Jha discuss the use of a "primary care first" model to screen and treat depression, emphasizing measurement-based care that can triage to specialty care when needed. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984454). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Depression https://emedicine.medscape.com/article/286759-overview USPSTF Screening for Depression in Adults https://www.uspreventiveservicestaskforce.org/uspstf/document/RecommendationStatementFinal/depression-in-adults-screening Depression Screening Patterns, Predictors, and Trends Among Adults Without a Depression Diagnosis in Ambulatory Settings in the United States https://pubmed.ncbi.nlm.nih.gov/29983110/ Primary versus Specialty Care Outcomes for Depressed Outpatients Managed With Measurement-Based Care: Results From STAR*D https://pubmed.ncbi.nlm.nih.gov/18247097/ The PHQ-9: Validity of a Brief Depression Severity Measure https://pubmed.ncbi.nlm.nih.gov/11556941/ VitalSign6: A Primary Care First (PCP-First) Model for Universal Screening and Measurement-Based Care for Depression https://pubmed.ncbi.nlm.nih.gov/31091770/ A Brief Measure for Assessing Generalized Anxiety Disorder: The GAD-7 https://pubmed.ncbi.nlm.nih.gov/16717171/ Prevalence and Impact of Diagnosed and Undiagnosed Depression in the United States https://pubmed.ncbi.nlm.nih.gov/36134073/ FDA Approves First Treatment for Post-partum Depression https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-post-partum-depression

Drs Madhukar Trivedi and Gregory Fonzo discuss the state of evidence and models for the use of psychedelic drugs in patients with major depressive disorder. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968561). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Depression https://emedicine.medscape.com/article/286759-overview What Is the Role of Transcranial Magnetic Stimulation (TMS) in the Treatment of Major Depressive Disorder (Clinical Depression)? https://www.medscape.com/answers/286759-14790/what-is-the-role-of-transcranial-magnetic-stimulation-tms-in-the-treatment-of-major-depressive-disorder-clinical-depression New Expert Guidance on Ketamine for Resistant Depression https://www.medscape.com/viewarticle/948097 Trending Clinical Topic: Psychedelics https://reference.medscape.com/viewarticle/971428 The Safety and Efficacy of COMP360 Psilocybin Therapy in Treatment-Resistant Depression: Results from a Phase IIb Randomized Controlled Trial https://j8g9v7z6.rocketcdn.me/wp-content/uploads/2022/05/Compass_APA_Poster_v5.1.pdf Psilocybin Effective Up to 12 Weeks in Severe Depression https://www.medscape.com/viewarticle/974935 Psychedelic Resting-State Neuroimaging: A Review and Perspective on Balancing Replication and Novel Analyses https://www.sciencedirect.com/science/article/pii/S0149763422001786 LSD Alters Dynamic Integration and Segregation in the Human Brain https://www.sciencedirect.com/science/article/pii/S1053811920311381 Center for Psychedelic Research & Therapy https://dellmed.utexas.edu/units/center-for-psychedelic-research-and-therapy MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study https://www.nature.com/articles/s41591-021-01336-3 The Emerging Science of Microdosing: A Systematic Review of Research on Low Dose Psychedelics (1955-2021) and Recommendations for the Field https://www.sciencedirect.com/science/article/pii/S0149763422001956 Oregon Psilocybin Services https://www.oregon.gov/oha/PH/PREVENTIONWELLNESS/Pages/Oregon-Psilocybin-Services.aspx

Drs Madhukar Trivedi and Andrew Krystal disentangle the complex relationship between sleep and major depressive disorder. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968560). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Biomarkers of Depression and Treatment Response (SUNSET) https://clinicaltrials.gov/ct2/show/NCT04581902 Customized Brain Stimulation: New Hope for Severe Depression https://www.medscape.com/viewarticle/960276 Closed-Loop Deep Brain Stimulation for Major Depression (PReSiDio) https://clinicaltrials.gov/ct2/show/NCT04004169 Insomnia in Patients With Depression: A STAR*D Report https://www.cambridge.org/core/journals/cns-spectrums/article/abs/insomnia-in-patients-with-depression-a-stard-report/2C9EB9396B44FD201E15927874FADC05 Prevalence of Obstructive Sleep Apnea in Suicidal Patients With Major Depressive Disorder https://www.sciencedirect.com/science/article/abs/pii/S0022395619302018?via%3Dihub Sleep Disorders as Core Symptoms of Depression https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181883/ Treating Insomnia in Depression: Insomnia Related Factors Predict Long-term Depression Trajectories https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841584/ Mirtazapine Tablet - Uses, Side Effects, and More https://www.webmd.com/drugs/2/drug-13706-4047/mirtazapine-oral/mirtazapine-oral/details Cognitive Behavioral Insomnia Therapy for Those With Insomnia and Depression: A Randomized Controlled Clinical Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806549/ Efficacy of Cognitive-Behavioral Therapy for Insomnia Combined With Antidepressant Pharmacotherapy in Patients With Comorbid Depression and Insomnia: A Randomized Controlled Trial https://www.psychiatrist.com/jcp/depression/cbt-for-insomnia-in-patients-with-comorbid-depression-and-insomnia/ Cognitive Behavioural Therapy for Insomnia (CBT-I) to Treat Depression: A Systematic Review https://www.sciencedirect.com/science/article/abs/pii/S0022399917308486 Eszopiclone - Uses, Side Effects, and More https://www.webmd.com/drugs/2/drug-92330/eszopiclone-oral/details Eszopiclone Co-Administered With Fluoxetine in Patients With Insomnia Coexisting With Major Depressive Disorder https://www.biologicalpsychiatryjournal.com/article/S0006-3223(06)00185-5/fulltext brexanolone (Rx) https://reference.medscape.com/drug/zulresso-brexanolone-1000299 Sleep Disturbances as an Evidence-Based Suicide Risk Factor https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613558/ Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT): A Randomized Clinical Trial https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.19030267 Insomnia Severity Index (ISI) https://reference.medscape.com/calculator/820/insomnia-severity-index-isi

Drs Madhukar Trivedi and Bradley Gaynes discuss the benefits of measurement-based care and how best to deliver it for patients with major depressive disorder. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968559). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Patient Health Questionnaire-9 (PHQ-9) https://reference.medscape.com/calculator/271/patient-health-questionnaire-9-phq-9 Clinical Results for Patients With Major Depressive Disorder in the Texas Medication Algorithm Project https://jamanetwork.com/journals/jamapsychiatry/fullarticle/482026 Depression, IV: STAR*D Treatment Trial for Depression https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.160.2.237#F1 APA Clinical Practice Guideline for the Treatment of Depression Across Three Age Cohorts https://www.apa.org/depression-guideline/guideline.pdf The Efficacy of Measurement-Based Care for Depressive Disorders: Systematic Review and Meta-analysis of Randomized Controlled Trials https://www.psychiatrist.com/jcp/depression/measurement-based-care-depression/ Final Recommendation Statement – Depression in Adults: Screening https://www.uspreventiveservicestaskforce.org/uspstf/document/RecommendationStatementFinal/depression-in-adults-screening Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians https://www.acpjournals.org/doi/10.7326/M15-2570 The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), Clinician Rating (QIDS-C), and Self-report (QIDS-SR): A Psychometric Evaluation in Patients With Chronic Major Depression https://www.biologicalpsychiatryjournal.com/article/S0006-3223(02)01866-8/fulltext Hamilton Depression Rating Scale (HAM-D or HDRS) https://reference.medscape.com/calculator/146/hamilton-depression-rating-scale-ham-d-or-hdrs Montgomery and Åsberg Depression Rating Scale (MADRS) https://www.apa.org/depression-guideline/montgomery-asberg-scale.pdf

How does the gut microbiome affect the brain? Madhukar Trivedi, MD, and Jane Foster, PhD, discuss the current evidence and clinical takeaways. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/968558). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Microbiome https://www.medscape.com/resource/microbiome Modulating Brain Function With Microbiota https://www.science.org/doi/10.1126/science.abo4220 A Systematic Review of Gut Microbiota Composition in Observational Studies of Major Depressive Disorder, Bipolar Disorder and Schizophrenia https://www.nature.com/articles/s41380-022-01456-3 Clinicaltrials.gov, search for phase 3 studies, recruiting, and keyword "probiotic" https://clinicaltrials.gov/ct2/results?term=probiotic&Search=Apply&recrs=a&age_v=&gndr=&type=&rslt=&phase=2 Review Article: The Future of Microbiome-Based Therapeutics https://onlinelibrary.wiley.com/doi/10.1111/apt.17049 A Randomized Controlled Trial of Dietary Improvement for Adults With Major Depression (The 'SMILES' Trial) https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0791-y Consumption of Fermented Milk Product With Probiotic Modulates Brain Activity https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839572/ Gut-Microbiota-Targeted Diets Modulate Human Immune Status https://www.cell.com/cell/fulltext/S0092-8674(21)00754-6

Madhukar Trivedi, MD, and Jonathan Downar, MD, review the evidence on the efficacy of transcranial magnetic stimulation as a treatment for major depressive disorder. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/968557). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Transcranial Magnetic Stimulation https://www.medscape.com/answers/286759-14790/what-is-the-role-of-transcranial-magnetic-stimulation-tms-in-the-treatment-of-major-depressive-disorder-clinical-depression Treatment-Resistant Depression https://www.medscape.com/viewarticle/431515_7 ECT https://emedicine.medscape.com/article/1525957-overview Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study https://www.nimh.nih.gov/funding/clinical-research/practical/stard FDA Clears TMS Device for Resistant Depression https://www.medscape.com/viewarticle/777357 FDA Clears Brain Stimulation Device for OCD https://www.medscape.com/viewarticle/900889 FDA Clears First Brain Stimulation Device to Help Smokers Quit https://www.medscape.com/viewarticle/936234 Neuroanatomy of Decision-making https://www.medscape.com/viewarticle/731957_5 Customized Brain Stimulation: New Hope for Severe Depression https://www.medscape.com/viewarticle/960276 Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression: A Multisite, Randomised, Sham-Controlled Trial https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(17)30371-1/fulltext High-Dose Spaced Theta-Burst TMS as a Rapid-Acting Antidepressant in Highly Refractory Depression https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837258/pdf/awx379.pdf Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.19070720 A pilot study of magnetic seizure therapy for treatment-resistant obsessive-compulsive disorder https://onlinelibrary.wiley.com/doi/10.1002/da.23097

Madhukar Trivedi, MD, and Manish Jha, MD, MBBS, review the evidence on the efficacy of esketamine and ketamine as a treatment for major depressive disorder. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/968556). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Symptom Clusters as Predictors of Late Response to Antidepressant Treatment https://www.psychiatrist.com/jcp/depression/symptom-clusters-predictors-late-response-antidepressant/ Intranasal Esketamine https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study https://www.nimh.nih.gov/funding/clinical-research/practical/stard Clinical Results for Patients With Major Depressive Disorder in the Texas Medication Algorithm Project https://jamanetwork.com/journals/jamapsychiatry/fullarticle/482026 Efficacy and Safety of Olanzapine/Fluoxetine Combination vs Fluoxetine Monotherapy Following Successful Combination Therapy of Treatment-Resistant Major Depressive Disorder https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207330/ Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816667/ Esketamine Nasal Spray for the Rapid Reduction of Depressive Symptoms in Major Depressive Disorder With Acute Suicidal Ideation or Behavior https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407443/ Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents https://clinicaltrials.gov/ct2/show/NCT04592809 Youth Depression and Suicide Research Network (YDSRN) https://clinicaltrials.gov/ct2/show/NCT04572321 The Neurobiology of Depression, Ketamine and Rapid-Acting Antidepressants: Is it Glutamate Inhibition or Activation? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165688/ Effect of Ketamine on Limbic GABA and Glutamate: A Human In Vivo Multivoxel Magnetic Resonance Spectroscopy Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507577/ Identifying Novel Mechanisms and Treatment Targets for Irritability and Aggression in Psychiatric Disorders https://www.nature.com/articles/s41386-021-01166-4 Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents https://clinicaltrials.gov/ct2/show/NCT04592809 Ketamine for Depression: An Update https://www.biologicalpsychiatryjournal.com/article/S0006-3223(16)32579-3/fulltext MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study https://www.nature.com/articles/s41591-021-01336-3 Trial of Psilocybin versus Escitalopram for Depression https://www.nejm.org/doi/full/10.1056/NEJMoa2032994 The Clinical Pharmacology and Potential Therapeutic Applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) https://onlinelibrary.wiley.com/doi/10.1111/jnc.15587