Psychiatry/Opioid dependence drugs

Opioid substitution & reversal

also: methadone · buprenorphine · naltrexone · naloxone · opioid dependence

Overview

Opioid substitution therapy plus the reversal agents. The full- vs partial-agonist distinction is the key point.

Mechanism

Methadone is a long-acting full µ-opioid agonist (stabilises, prevents withdrawal/craving). Buprenorphine is a partial µ-agonist (ceiling effect → safer in overdose; can precipitate withdrawal if given too soon). Naloxone is a short-acting antagonist (overdose reversal); naltrexone is a long-acting antagonist (relapse prevention once abstinent).

Indications

Opioid dependence (maintenance / detox)
Opioid overdose (naloxone)
Relapse prevention after detox (naltrexone)

The agents

Methadonefull µ-agonist

OD, supervised

QT prolongation; overdose/respiratory depression risk; long t½.

Buprenorphinepartial µ-agonist

sublingual

Ceiling effect (safer); precipitated withdrawal if given while opioids on board.

Naloxoneantagonist (overdose)

IV/IM/intranasal

Short t½ — repeat/infuse; take-home kits.

Naltrexoneantagonist (relapse prevention)

oral

Only once detoxed (precipitates withdrawal).

Adverse effects

Methadone: respiratory depression, QT prolongation, overdoseserious

Buprenorphine: precipitated withdrawalserious

Constipation, sedationcommon

Cautions & contraindications

Methadone with other QT/sedative drugsall

Naltrexone while still using opioidsall

Precipitates withdrawal.

Interactions

Methadone + QT-prolonging/sedatives
Other CNS depressants

Monitoring & kinetics

Supervised consumption initially; methadone ECG; urine drug screens

Oral/sublingual substitution; naloxone IV/IM/intranasal.

Source: NICE — Opioid dependence · BNF — Opioid dependence