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Methadone Induction Risk — MRCPsych Paper B MCQ

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HardSubstance MisuseMethadone Induction RiskMRCPsych Paper B

A 38-year-old man with heroin dependence begins supervised once-daily oral methadone 30 mg. By day 4 his pre-dose withdrawal symptoms have settled, but staff note he is increasingly drowsy for several hours after each dose, although his daily dose has not been increased. He denies alcohol, benzodiazepines, gabapentinoids and additional opioids, and urine testing supports this. Which treatment period carries the greatest risk of fatal respiratory depression from prescribed methadone alone?

Educational content. Not a substitute for clinical judgement or local policy.

Reveal the answer and explanation

Correct answer: E — The first 1 to 2 weeks of induction and dose titration

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

B is correct. Methadone has a long, highly variable half-life, so plasma and tissue concentrations continue to rise for roughly 3–10 days on an unchanged daily dose; the UK SmPC warns that respiratory depression may not be fully apparent for a week or two. The vignette's progressive post-dose drowsiness without a dose increase is classic accumulation before steady state, and this induction/titration window carries the highest methadone-related mortality, hence low starting doses and cautious increments. A is wrong: stable long-term maintenance is comparatively protective. C reduces prescribed exposure (relapse after lost tolerance is a separate risk). D permits observation and limits diversion but cannot prevent pharmacokinetic accumulation. E is wrong: benzodiazepines potentiate respiratory depression but are not necessary for fatal methadone toxicity.

Reference: Methadone Hydrochloride Sugar Free 1mg/1ml Oral Solution — Summary of Product Characteristics, section 4.4 Special warnings and precautions (accumulation and delayed respiratory depression), electronic medicines compendium, current version. https://www.medicines.org.uk/emc/product/6689/smpc