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

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

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

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

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 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 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 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/