Key Facts

Opioid substitution therapy is the gold standard treatment for opioid dependence. It replaces short-acting illicit opioids with longer-acting prescribed alternatives, stabilising the patient and enabling psychosocial recovery. It is one of the most evidence-based treatments in all of addiction medicine.

Epidemiology

• Approximately 140,000 people in England receive OST at any one time
• ~50% prescribed methadone, ~30% buprenorphine, remainder mixed or other
• Retention in OST at 12 months: approximately 60-70% for methadone, 50-60% for buprenorphine
• Adequate-dose OST associated with ~50% reduction in all-cause mortality

Aetiology/Rationale

• Pharmacological replacement: provides steady-state opioid receptor occupancy, preventing withdrawal and reducing craving
• Cross-tolerance: blocks euphoric effect of additional illicit opioids at adequate doses
• Harm reduction: eliminates injecting and associated risks (BBV, abscesses, endocarditis)
• Stabilisation: enables engagement with psychosocial support, housing, employment
• Gateway to recovery: OST as platform for eventual detoxification when patient is ready

Pathophysiology of Action

• Methadone: full μ opioid receptor agonist; oral bioavailability ~80%; half-life 24-36 hours; steady state reached at 3-5 days
• Buprenorphine: partial μ agonist and κ antagonist; sublingual bioavailability ~30%; half-life 24-48 hours; ceiling effect on respiratory depression (safer in overdose)
• Naloxone component (in Suboxone): poorly absorbed sublingually; blocks opioid effect if crushed and injected → deterrent to diversion
• Buvidal (CAM2038): depot buprenorphine; subcutaneous injection forming solid depot; slow release over 1 week or 1 month

Assessment Before Starting OST

• Comprehensive drug and alcohol history: substances used, route, frequency, quantity, duration
• Confirm opioid dependence: objective evidence (withdrawal signs, urine drug screen, tolerance)
• Risk assessment: overdose risk, injecting behaviour, BBV status, mental health, social circumstances, pregnancy
• Physical examination: injection sites, signs of liver disease, general health
• Mental health screening: depression, anxiety, psychosis, suicidality

Indications for OST

• Confirmed opioid dependence (typically heroin or prescription opioid)
• Failed attempts at abstinence-based approaches
• Patient willing to engage with treatment programme
• Risk assessment supports benefit of OST over alternative approaches

Monitoring During Treatment

• Supervised consumption: observe ingestion for at least 3 months; assess for stability before allowing take-home doses
• Urine drug screening: regular testing for illicit drug use and prescribed medication compliance
• Clinical review: regular appointments to assess progress, side effects, dose adequacy
• Key worker sessions: structured psychosocial support alongside prescribing

Red Flags

• Excessive sedation on current dose: risk of over-dosing, especially in first 2 weeks
• Continued injecting: dose may be inadequate or patient may need alternative approach
• Concurrent benzodiazepine or alcohol use: dramatically increases overdose risk with methadone
• QTc >500 ms on methadone: consider switch to buprenorphine
• Pregnancy: methadone or buprenorphine should be continued (not detoxed); specialist obstetric/addiction liaison required
• Missed doses: if 3+ days missed, dose must be reassessed (loss of tolerance)

Bedside

• COWS score: before starting buprenorphine (must be ≥12 for safe induction)
• Urine drug screen: baseline and ongoing; confirm opioid use, screen for other substances
• Pregnancy test: in women of childbearing age before initiation
• Observations: HR, BP, RR — especially during titration

Bloods

• LFTs: baseline hepatic function (methadone and buprenorphine are hepatically metabolised)
• Blood-borne virus screen: hepatitis B, hepatitis C, HIV
• FBC: baseline
• U&Es: baseline renal function

Imaging

• Not routinely required for OST
• Echocardiography: if clinical suspicion of endocarditis
• FibroScan: if hepatitis C positive

Special Tests

• ECG: recommended before starting methadone and at dose changes >100 mg/day; check QTc (concern >450 ms, high risk >500 ms)
• QTc monitoring: repeat ECG at dose stabilisation, annually, and if symptoms of arrhythmia
• Hair or oral fluid testing: may be used for longer-term compliance monitoring

Non-pharmacological

• Psychosocial interventions (NICE CG51): keyworker support, structured counselling, contingency management
• Harm reduction: needle exchange, safer injecting advice, naloxone provision
• Social stabilisation: housing, benefits, employment support, family interventions
• Recovery support: mutual aid (NA, SMART Recovery), peer mentoring, recovery communities

Pharmacological — Methadone Initiation

• Starting dose: 10-30 mg OD (depending on risk assessment, tolerance level, concurrent substance use)
• Titration: increase by 5-10 mg every 3-5 days (max increase 30 mg in first week)
• Optimal dose: 60-120 mg/day — individualised based on clinical response
• Supervised consumption: mandatory initially; daily attendance at community pharmacy
• Formulation: 1 mg/mL oral solution (preferred to reduce diversion risk)
• Drug interactions: CYP3A4 substrate — caution with inhibitors (fluconazole, erythromycin) and inducers (rifampicin, carbamazepine, phenytoin)

Pharmacological — Buprenorphine Initiation

• Prerequisite: patient must be in opioid withdrawal (COWS ≥12) — typically ≥12 hours after last heroin dose, ≥24-48 hours after last methadone dose
• Starting dose: 4 mg sublingual on day 1; can give further 4 mg after 2-4 hours if needed
• Day 2: 8 mg; titrate over first week to 8-24 mg/day
• Supervised consumption: as per methadone
• Buvidal: weekly SC injection (8-32 mg) or monthly (64-160 mg); after stabilisation on sublingual buprenorphine

Surgical

• Not applicable to OST

Referral Criteria

• Community drug and alcohol team: all patients with opioid dependence for assessment
• Specialist addiction psychiatrist: complex presentations, dual diagnosis, failed treatment
• Perinatal addiction service: pregnant women on OST
• Pain management: patients with chronic pain on OST
• Hepatology/BBV services: hepatitis C treatment, HIV co-management

Outcomes

• OST retention at 1 year: 60-70% (methadone), 50-60% (buprenorphine)
• Reduction in illicit opioid use: ~60-70% of patients significantly reduce or stop illicit heroin while on adequate-dose OST
• All-cause mortality reduction: approximately 50% while on OST
• Reduction in criminal activity: ~50% reduction in acquisitive crime
• Duration of treatment: often years; no maximum recommended duration; many patients benefit from long-term or indefinite OST

Complications

• Methadone-related: QTc prolongation and risk of torsades de pointes (especially doses >100 mg/day or with interacting drugs); constipation; weight gain; dental problems; hyperhidrosis
• Buprenorphine-related: precipitated withdrawal if initiated too early; headache; nausea; constipation; hepatotoxicity (rare at therapeutic doses)
• First 2 weeks of treatment: highest risk of overdose death (especially methadone titration phase)
• Drop-out from treatment: associated with return to illicit use and increased mortality
• Stigma: can affect engagement with healthcare and employment

Methadone vs Buprenorphine Comparison

Take-Home Dose Criteria