Key Facts

Opioid use disorder (OUD) is one of the most significant substance misuse problems in the UK. Heroin (diamorphine) is the most commonly injected drug, but prescription opioid misuse is an increasing concern. Opioid-related deaths have risen to record levels in recent years.

Epidemiology

• ~260,000 high-risk opioid users in England; ~310,000 across the UK
• Drug-related deaths in England and Wales: approximately 4,900/year (2021); opioids involved in ~50%
• Mean age of opioid-dependent population is rising (ageing cohort): now ~40-45 years
• Male:female ratio approximately 3:1
• Hepatitis C: prevalence approximately 50% among people who inject drugs (PWID)
• HIV: prevalence approximately 1-2% among PWID in England (higher in London)

Aetiology

• Neurobiological: opioids activate μ (mu) opioid receptors in the mesolimbic reward pathway (VTA → nucleus accumbens) → dopamine release → reinforcement
• Tolerance: receptor desensitisation and downregulation with chronic use
• Physical dependence: neuroadaptive changes; abrupt cessation → withdrawal
• Psychological factors: self-medication for trauma, chronic pain, mental illness; adverse childhood experiences (ACEs)
• Social factors: deprivation, homelessness, criminal justice involvement, peer influence
• Prescription opioid pathway: escalation from legitimate prescribing → dependence → illicit use

Pathophysiology

• Acute opioid effects: analgesia, euphoria, sedation, respiratory depression, miosis, constipation, nausea
• Chronic use → neuroadaptation: upregulation of cAMP pathway, noradrenergic hyperactivity (locus coeruleus)
• Withdrawal → sympathetic overdrive and rebound hyperalgesia: the basis of withdrawal symptoms
• Cross-tolerance exists between different opioids but is incomplete

Opioid Intoxication

• Miosis (pinpoint pupils) — classic sign
• Respiratory depression: reduced rate and depth
• Sedation/drowsiness: nodding
• Euphoria: sense of wellbeing
• Hypotension and bradycardia
• Constipation and reduced bowel sounds

Opioid Withdrawal (onset 8-24 hours after last heroin dose)

• Early features: yawning, lacrimation, rhinorrhoea, piloerection (gooseflesh — origin of "cold turkey")
• Progressive: dilated pupils, sweating, nausea, vomiting, diarrhoea, abdominal cramps
• Later features: muscle aches, insomnia, agitation, tachycardia, hypertension
• Peak: typically 36-72 hours after last heroin use; longer with methadone (72-96 hours)
• Duration: acute symptoms resolve over 5-10 days (heroin) or 2-3 weeks (methadone)

Complications of Injecting Drug Use

• Blood-borne viruses: hepatitis B, hepatitis C, HIV
• Bacterial infections: cellulitis, abscesses, endocarditis (especially right-sided — S. aureus), osteomyelitis, septic arthritis
• Vascular: DVT, PE, pseudoaneurysm, arterial occlusion
• Wound botulism: rare but life-threatening
• Groin injection complications: femoral vein thrombosis, ischaemia

Red Flags

• Respiratory rate <8/min or oxygen saturation <92%: opioid overdose — give naloxone immediately
• Unconscious with pinpoint pupils: overdose until proven otherwise
• Fever and new murmur in IVDU: infective endocarditis
• Injection site swelling with crepitus: necrotising fasciitis/wound botulism
• Sudden limb ischaemia: inadvertent intra-arterial injection

Bedside

• Clinical Opiate Withdrawal Scale (COWS): 11-item assessment; <5 no withdrawal, 5-12 mild, 13-24 moderate, 25-36 moderately severe, >36 severe
• Observations: RR, SpO2 (critical), HR, BP, temperature, GCS
• Pupil assessment: miosis in intoxication, mydriasis in withdrawal
• Urine drug screen: confirm opioid use and identify other substances
• Injection site examination: track marks, abscesses, signs of DVT

Bloods

• FBC: anaemia (chronic disease), leucocytosis (infection)
• LFTs: hepatitis C-related liver disease
• U&Es: renal function (rhabdomyolysis risk)
• CRP: infection screening
• Blood-borne virus screen: hepatitis B surface antigen, hepatitis C antibody (reflex PCR if positive), HIV test (with consent)
• Blood cultures: if febrile or suspected endocarditis
• CK: if prolonged immobility or seizures (rhabdomyolysis)

Imaging

• Chest X-ray: aspiration pneumonia, pulmonary oedema (non-cardiogenic with heroin)
• Echocardiography: if endocarditis suspected (transthoracic ± transoesophageal)
• Doppler ultrasound: if DVT suspected in injecting limb

Special Tests

• ECG: QTc prolongation (methadone is a known cause — check before and during treatment)
• FibroScan: non-invasive liver fibrosis assessment if hepatitis C positive
• Hepatitis C PCR: if antibody positive — confirms active viraemia
• Dry blood spot testing: available for BBV screening in community settings

Non-pharmacological

• Harm reduction: needle and syringe programmes, safe injecting advice, vein care
• Psychosocial interventions: keyworker support, structured counselling, contingency management (NICE TA114)
• Mutual aid: Narcotics Anonymous, SMART Recovery
• Social support: housing, employment, benefits advice, criminal justice liaison
• Hepatitis C treatment: direct-acting antivirals (DAAs) — cure rate >95%; treat and prevent re-infection
• Vaccination: hepatitis B vaccination for all PWID; tetanus, influenza

Pharmacological

• Opioid Substitution Therapy (NICE CG52):
  • Methadone (oral solution): start 10-30 mg OD (risk assessment-dependent); titrate over 2 weeks to 60-120 mg OD; supervised consumption initially
    • Long-acting μ agonist; T½ 24-36 hours
    • QTc prolongation risk: ECG before and during treatment
  • Buprenorphine (Subutex): start 4 mg SL on day 1 (must be in withdrawal — COWS ≥12); titrate to 8-24 mg OD
    • Partial μ agonist and κ antagonist; ceiling effect on respiratory depression
    • Suboxone (buprenorphine/naloxone): reduces diversion risk
    • Buvidal (prolonged-release buprenorphine injection): weekly or monthly SC injection; improves adherence
  • Supervised consumption: recommended for at least first 3 months of OST
• Symptomatic withdrawal management (if detoxification chosen):
  • Lofexidine 0.2 mg BD, titrate to max 2.4 mg/day: alpha-2 adrenergic agonist; reduces noradrenergic withdrawal symptoms
  • Loperamide for diarrhoea, metoclopramide for nausea, ibuprofen for aches
• Naltrexone 50 mg OD: opioid antagonist for relapse prevention after detoxification; patient must be opioid-free for ≥7-10 days

Surgical

• Abscess drainage: for injection site abscesses
• Cardiac surgery: valve replacement for endocarditis in selected cases

Referral Criteria

• Community drug team: all patients with opioid dependence for assessment and OST
• Inpatient detoxification: failed community treatment, complex co-morbidity, pregnancy
• Hepatology: hepatitis C with significant fibrosis; all hepatitis C-positive patients should access DAA treatment
• Psychiatry: severe co-morbid mental illness, suicidality
• Infectious diseases: HIV, complex BBV management, endocarditis

Mortality

• Drug-related deaths: opioid-related deaths approximately 2,300/year in England and Wales
• OST reduces all-cause mortality by ~50% compared to no treatment
• First 4 weeks of OST and first 4 weeks after leaving treatment are highest-risk periods for overdose death
• Overdose risk highest after periods of abstinence (loss of tolerance): prison release, after detoxification
• 10-year mortality for untreated heroin dependence: approximately 5-10%

Complications

• Overdose death: respiratory depression; risk increased with polydrug use (especially benzodiazepines and alcohol)
• Hepatitis C cirrhosis: if untreated; now curable with DAAs
• Infective endocarditis: typically right-sided (tricuspid); S. aureus most common; mortality ~20-30%
• DVT/PE: common with groin injection
• Social consequences: homelessness, imprisonment, family breakdown, poverty
• Neonatal abstinence syndrome: in babies born to opioid-dependent mothers

Clinical Opiate Withdrawal Scale (COWS) Summary

Comparison of OST Options

Key Policy and Guidance