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Methadone NMDA OIH — SCE Medical Oncology MCQ

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HardSupportive & Palliative OncologyMethadone NMDA OIHSCE Medical Oncology

A 65-year-old woman with cancer develops opioid-induced hyperalgesia. She is on high-dose morphine and reports diffuse allodynia with generalised pain worse than her cancer pain. Her oncologist considers methadone rotation. What makes methadone uniquely suited for OIH?

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Correct answer: D — Methadone has intrinsic NMDA receptor antagonist activity in addition to µ-opioid agonism — NMDA antagonism counteracts the central sensitisation that drives OIH, making methadone particularly effective for switching from OIH-causing opioids

Methadone's unique pharmacology: µ-opioid agonist + NMDA receptor antagonist + serotonin/noradrenaline reuptake inhibitor. The NMDA antagonism directly addresses the central sensitisation underlying OIH. Caution: long/variable half-life (15-60 hours), QTc prolongation risk, complex equianalgesic conversion ratios. Specialist palliative care guidance essential for methadone initiation.

Reference: Palliative Care Formulary; NICE CG140; ESMO Pain Management