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