Opioid Misuse and Dependence

Pharmacology Overview

Opioids are a drug class, not one specific drug. Common examples include: ^[Ref]

• Morphine
• Codeine
• Fentanyl
• Oxycodone
• Heroin (diamorphine)

MoA: ^[Ref]

• Primarily a μ (mu) opioid receptor agonist
• μ-receptor activation causes:
  • ↓ Presynaptic Ca²⁺ influx → ↓ neurotransmitter release
  • ↑ Postsynaptic K⁺ efflux → neuronal hyperpolarisation

Clinical Features and Diagnosis

For clinical features, diagnosis and management of acute opioid toxicity / overdose, see the Opioid Toxicity and Overdose article.

Opioid Intoxication Features

This refers to the expected acute effects of opioid use: ^[Ref1][Ref2]

• CNS features
  • Euphoria or a sense of relaxation
  • Analgesia
  • Sedation / drowsiness
• Miosis
• Pruritus
• GI features
  • Nausea and vomiting
  • Constipation

Opioid Withdrawal Features

^[Ref1][Ref2]

Management

There are 2 broad consecutive phases:

1. Detoxification (“getting clean”): short-term process of safely withdrawing opioids in a dependent patient while minimising withdrawal symptoms
2. Relapse prevention (“staying clean”): following successful detoxification, treatment aims to maintain abstinence and reduce the risk of relapse

1. Detoxification

Detoxification Setting

1st line: community-based detoxification programme (up to 12 weeks) ^{[NICE CG52]}

Indications for residential and inpatient detoxification: ^{[NICE CG52]}

• Failed previous community-based detoxification attempts
• Patient suffers from significant comorbid physical or mental health problems that require structured medical and/or nursing care
• Require complex polydrug detoxification (e.g. concurrent withdrawal from alcohol or benzodiazepines)
• Patient experiencing severe social or housing instability

Psychosocial Intervention

Contingency management is the only intervention with clear evidence of effectiveness ^{[NICE CG52]}

• Also known as incentives for abstinence
• Involves providing structured, voluntary incentives (like vouchers, modest financial rewards, clinical privileges) to reinforce positive behaviours such as drug-free urine screens or session attendance

Pharmacological Intervention

There are 2 main approaches to managing opioid withdrawal thus achieving detoxification:

• Substitution therapy: use a longer-acting opioid agonist or partial agonist (e.g. methadone or buprenorphine) to replace the misused opioid and reduce the dose gradually
• Symptomatic relief: use non-opioid adjunctive medications to relieve specific withdrawal symptoms

Substitution Therapy

1st line: ^{[NICE CG52]}

• Methadone (opioid receptor full agonist), OR
• Buprenorphine (opioid receptor partial agonist)

The choice between the 2 substitution agents depends on the following factors: ^[BNF][DHSC]

Adjuvant / Symptomatic Treatment

Lofexidine (α2-adrenergic receptor agonist): reduces sympathetic outflow, helping relieve autonomic opioid withdrawal symptoms such as sweating, tachycardia and agitation ^{[NICE CG52][BNF]}

• An alternative to standard opioid substitution (i.e. methadone and buprenorphine) in those with mild or uncertain dependence (often <18 y/o)
• Can also be used as an adjuvant to standard opioid substitution (i.e. methadone and buprenorphine)

Symptom-directed management: ^[BNF]

• Diarrhoea → loperamide 
• Stomach cramps → mebeverine
• Headache and myalgia → paracetamol and NSAIDs
• Nausea and vomiting → metoclopramide or prochlorperazine
• Insomnia → short-acting benzodiazepines or zopiclone

Topical rubefacients can be used to manage muscle pain associated with methadone hydrochloride withdrawal

2. Relapse Prevention

Psychosocial Intervention

Contingency management is the only intervention with clear evidence of effectiveness ^{[NICE CG52]}

• Also known as incentives for abstinence
• Involves providing structured, voluntary incentives (like vouchers, modest financial rewards, clinical privileges) to reinforce positive behaviours such as drug-free urine screens or session attendance

Pharmacological Intervention

Primary option: naltrexone ^[BNF]

• MoA: opioid-receptor antagonist 
• Naltrexone can only be initiated after successful detoxification and remaining opioid-free for at least 7-10 days ^[BNF]

Opioid Dependence in Pregnancy

Key points: ^[BNF]

• Avoid acute opioid withdrawal during pregnancy as it can cause fetal compromise
• Opioid substitution therapy is recommended during pregnancy because it carries a lower risk to the fetus than continued use of illicit drugs
  • 1st trimester: avoid withdrawal because it is associated with an increased risk of spontaneous miscarriage
  • 2nd trimester: if withdrawal is undertaken, methadone or buprenorphine should be reduced gradually
  • 3rd trimester: further withdrawal is not recommended because even mild maternal withdrawal is associated with fetal distress, stillbirth and neonatal mortality

If the patient is already stabilised on methadone or buprenorphine when pregnancy occurs, substitution therapy should generally be continued ^[BNF]

References