Ketamine NMDA Psychosis — MRCPsych Paper B MCQ

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HardLiaison PsychiatryKetamine NMDA PsychosisMRCPsych Paper B

A 30-year-old with no psychiatric history receives ketamine as the sole anaesthetic for an emergency procedure. During recovery, while alert and correctly oriented, they develop auditory hallucinations, persecutory ideas, affective flattening and impaired working memory. All symptoms resolve within 2 hours. Which receptor action most plausibly accounts for this combination of transient positive, negative and cognitive schizophrenia-like symptoms?

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Correct answer: A — NMDA receptor antagonism

Explanation lettering: B = shown as A · A = shown as B · D = shown as C · E = shown as D · C = shown as E

B is correct. Ketamine antagonises NMDA-type glutamate receptors, and the UK SmPC directly links its NMDA receptor activity with psychiatric, including psychotic, effects. Acute ketamine challenge can produce positive symptoms, negative symptoms and cognitive impairment, supporting the glutamatergic NMDA-hypofunction model of psychosis. The close temporal relationship, preserved orientation and complete resolution favour a transient drug-induced psychotomimetic syndrome rather than postoperative delirium or a primary psychotic disorder. 5-HT2A agonism is characteristic of classical psychedelics. D2 agonism can provoke predominantly positive psychotic symptoms but is not ketamine's principal receptor action. Ketamine has opioid-receptor interactions, but these do not primarily explain its schizophrenia-like effects. GABA-A antagonism would more characteristically cause marked neuronal excitation and seizures.

Reference: Panpharma UK Ltd. Ketamine 50 mg/ml Solution for Injection, Summary of Product Characteristics, sections 4.8 and 5.1. Updated 4 February 2025. https://www.medicines.org.uk/emc/product/2420/smpc