Psych · Psychopharmacology — ketamine and esketamine
Ketamine and esketamine
Also known as Spravato · Esketamine nasal spray · Racemic ketamine depression · IV ketamine TRD · NMDA antagonist antidepressant
Exam-exhaustive fellowship reference on ketamine and esketamine for treatment-resistant depression — pharmacology, 0.5 mg/kg IV protocols, IN esketamine dosing and supervised observation, TRANSFORM/SUSTAIN/ASPIRE evidence, ELEKT-D vs ECT, dissociation and BP monitoring, abuse and bladder cautions, special populations. FRANZCP-primary, globally tagged.
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10 MCQs with explanations
Target exams
FRANZCPMRCPsychABPNMD-DNBNEET-SS
Red flags
Uncontrolled hypertension, aneurysmal disease, arteriovenous malformation, or prior intracerebral haemorrhage — major contraindications for esketamine/ketamine programmesTake-home or unsupervised dosing of regulated esketamine — forbidden; clinic observation is the safety systemRapid drop in suicidal ideation after a dose is not a licence to stop safety planning or discharge without structureNew psychosis, mania, or severe dissociation with agitation — stop session, contain, reassess diagnosis and substance useHistory of ketamine misuse, diversion risk, or chronic recreational use with urinary symptoms — structured consent and clinic-only administrationDriving, operating machinery, or unescorted discharge in the observation window after dosing
Meet the patient
A 44-year-old teacher, third depressive episode, eleven months unwell. Sertraline to 200 mg for ten weeks, then venlafaxine XR to 225 mg for nine weeks, both taken and both documented. No mania ever. No psychosis. She has stopped driving because she keeps thinking about the bridge on her commute.[4][21]
Her GP has read about ketamine and wants to know why she cannot have it tomorrow. The examiner wants to know something narrower: what has to be true before you put this woman in a dosing chair?[9][21]
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References23Show ledgerHide ledger
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- [2]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
- [3]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
- [4]Newport DJ, Carpenter LL, McDonald WM, et al. Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. Am J Psychiatry, 2015.PMID 26423481
- [5]Coyle CM, Laws KR The use of ketamine as an antidepressant: a systematic review and meta-analysis. Hum Psychopharmacol, 2015.PMID 25847818
- [6]Li N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science, 2010.PMID 20724638
- [7]Zanos P, Moaddel R, Morris PJ, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature, 2016.PMID 27144355
- [8]Singh JB, Fedgchin M, Daly E, et al. Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study. Biol Psychiatry, 2016.PMID 26707087
- [9]Sanacora G, Frye MA, McDonald W, et al. A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry, 2017.PMID 28249076
- [10]Short B, Fong J, Galvez V, et al. Side-effects associated with ketamine use in depression: a systematic review. Lancet Psychiatry, 2018.PMID 28757132
- [11]Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study. Am J Psychiatry, 2018.PMID 29656663
- [12]Wilkinson ST, Ballard ED, Bloch MH, et al. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. Am J Psychiatry, 2018.PMID 28969441
- [13]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
- [14]Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1). Int J Neuropsychopharmacol, 2019.PMID 31290965
- [15]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
- [16]Phillips JL, Norris S, Talbot J, et al. Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. Am J Psychiatry, 2019.PMID 30922101
- [17]Ochs-Ross R, Daly EJ, Zhang Y, et al. Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression-TRANSFORM-3. Am J Geriatr Psychiatry, 2020.PMID 31734084
- [18]Wajs E, Aluisio L, Holder R, et al. Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2). J Clin Psychiatry, 2020.PMID 32316080
- [19]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
- [20]Ionescu DF, Fu DJ, Qiu X, et al. 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). Int J Neuropsychopharmacol, 2021.PMID 32861217
- [21]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
- [22]Ceban F, Rosenblat JD, Kratiuk K, et al. Prevention and Management of Common Adverse Effects of Ketamine and Esketamine in Patients with Mood Disorders. CNS Drugs, 2021.PMID 34363603
- [23]Anand A, Mathew SJ, Sanacora G, et al. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. N Engl J Med, 2023.PMID 37224232