Ketamine and esketamine — consultant viva · Psych Vivas

Prompt

Examiner places cards: 0.5 mg/kg, TRANSFORM-2, SUSTAIN-1, ASPIRE, ELEKT-D, aneurysm history, unsupervised take-home spray, dissociation in recovery.

Station structure

Time: 8–10 minutes. Depth: consultant teaching registrar. Expect named trials, dose scaffolds, and safety protocols without inventing local funding codes as universal law.[7]

Core questions and model points

What are ketamine and esketamine? Racemic IV NMDA antagonist antidepressant protocols vs S-enantiomer supervised nasal spray; rapid onset via NMDA–AMPA–BDNF–mTOR plasticity model.[1][8][7]
Classic IV dose? Approximately 0.5 mg/kg over 40 minutes; Murrough midazolam-controlled design supports efficacy beyond pure expectancy critiques.[1][2]
Esketamine TRD programme? Supervised 56/84 mg with oral AD; TRANSFORM-2 flexible dose short-term efficacy; SUSTAIN-1 continuation prevents relapse.[3][4]
SI populations? ASPIRE/Canuso: rapid depressive/SI symptom reduction signals within comprehensive standard of care — not a suicide-proof guarantee.[5]
Contraindications? Uncontrolled major vascular risk (aneurysm, ICH history), inability to observe, active problematic misuse without structure.[7]
Take-home spray? No for regulated programmes — supervision and observation are the safety system.[3][7]
vs ECT? ELEKT-D noninferiority for nonpsychotic TRD; psychotic depression/catatonia/pregnancy severe depression still often ECT-led.[6]

Pass criteria

Correct IV and IN dose scaffolds and observation culture.[1][3]
TRANSFORM/SUSTAIN/ASPIRE/ELEKT-D one-liners accurate.[3][4][5][6]
Safety: BP, dissociation, no unsupervised dosing, ongoing risk plan.[7]
Mechanism one-liner without speculative fluff.[8]

References

[1]Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry, 2006.PMID 16894061
[2]Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry, 2013.PMID 23982301
[3]Popova V, Daly EJ, Trivedi M, et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry, 2019.PMID 31109201
[4]Daly EJ, Trivedi MH, Janik A, et al. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry, 2019.PMID 31166571
[5]Fu DJ, Ionescu DF, Li X, et al. Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I). J Clin Psychiatry, 2020.PMID 32412700
[6]Anand A, Mathew SJ, Sanacora G, et al. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. N Engl J Med, 2023.PMID 37224232
[7]McIntyre RS, Rosenblat JD, Nemeroff CB, et al. Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. Am J Psychiatry, 2021.PMID 33726522
[8]Li N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science, 2010.PMID 20724638

Core questions and model points

What are ketamine and esketamine? Racemic IV NMDA antagonist antidepressant protocols vs S-enantiomer supervised nasal spray; rapid onset via NMDA–AMPA–BDNF–mTOR plasticity model.[1][8][7]

Classic IV dose? Approximately 0.5 mg/kg over 40 minutes; Murrough midazolam-controlled design supports efficacy beyond pure expectancy critiques.[1][2]

Esketamine TRD programme? Supervised 56/84 mg with oral AD; TRANSFORM-2 flexible dose short-term efficacy; SUSTAIN-1 continuation prevents relapse.[3][4]

SI populations? ASPIRE/Canuso: rapid depressive/SI symptom reduction signals within comprehensive standard of care — not a suicide-proof guarantee.[5]

Contraindications? Uncontrolled major vascular risk (aneurysm, ICH history), inability to observe, active problematic misuse without structure.[7]

Take-home spray? No for regulated programmes — supervision and observation are the safety system.[3][7]

vs ECT? ELEKT-D noninferiority for nonpsychotic TRD; psychotic depression/catatonia/pregnancy severe depression still often ECT-led.[6]

Pass criteria

Correct IV and IN dose scaffolds and observation culture.[1][3]

TRANSFORM/SUSTAIN/ASPIRE/ELEKT-D one-liners accurate.[3][4][5][6]

Safety: BP, dissociation, no unsupervised dosing, ongoing risk plan.[7]

Mechanism one-liner without speculative fluff.[8]

References

[1]Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry, 2006.PMID 16894061
[2]Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry, 2013.PMID 23982301
[3]Popova V, Daly EJ, Trivedi M, et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry, 2019.PMID 31109201
[4]Daly EJ, Trivedi MH, Janik A, et al. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry, 2019.PMID 31166571
[5]Fu DJ, Ionescu DF, Li X, et al. Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I). J Clin Psychiatry, 2020.PMID 32412700
[6]Anand A, Mathew SJ, Sanacora G, et al. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. N Engl J Med, 2023.PMID 37224232
[7]McIntyre RS, Rosenblat JD, Nemeroff CB, et al. Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. Am J Psychiatry, 2021.PMID 33726522
[8]Li N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science, 2010.PMID 20724638