Opioid Use Disorder - Assessment, Pharmacotherapy, and Harm Reduction

Medical Student Learning Objective: MS_PSY_013

Definition / Overview

Opioid use disorder (OUD) is a chronic, relapsing neurobiological condition characterised by compulsive opioid use despite significant adverse consequences. It encompasses dependence on illicit opioids (heroin, illicitly manufactured fentanyl), prescription opioids (oxycodone, morphine, codeine), and pharmaceutical opioids obtained outside therapeutic channels.

DSM-5 Diagnostic Criteria (summary)

A problematic pattern of opioid use leading to clinically significant impairment or distress, with ≥2 of 11 criteria within a 12-month period, including: - Tolerance and withdrawal - Using more than intended, unsuccessful attempts to cut down - Craving, failure to fulfil role obligations - Continued use despite physical or psychological harm - Social and occupational impairment

Severity grading: - Mild: 2-3 criteria - Moderate: 4-5 criteria - Severe: ≥6 criteria

Australian Epidemiological Context

• Opioid-related harms - including overdose deaths - are a significant public health burden in Australia
• Both illicit (heroin) and pharmaceutical opioid misuse contribute substantially
• Aboriginal and Torres Strait Islander peoples experience disproportionate burden; culturally safe, community-led approaches are essential
• Medications for OUD (MOUD) - buprenorphine/naloxone and methadone - are PBS-listed and are the standard of care

Pathophysiology

Neurobiological Basis

• Opioids act at mu (μ), kappa (κ), and delta (δ) opioid receptors - G-protein coupled receptors that inhibit adenylyl cyclase, reduce neuronal firing, and decrease neurotransmitter release
• Chronic opioid exposure leads to receptor downregulation and desensitisation → tolerance
• Abrupt cessation removes tonic opioid suppression → rebound hyperadrenergic state = withdrawal
• Dopaminergic reward pathways (nucleus accumbens, VTA) are sensitised → craving and compulsive drug-seeking behaviour

Opioid Withdrawal Physiology

Withdrawal is profoundly uncomfortable but rarely life-threatening in otherwise healthy adults (contrast with benzodiazepine or alcohol withdrawal). The syndrome results from adrenergic rebound and autonomic hyperactivity.

Clinical Features

The Clinical Opiate Withdrawal Scale (COWS)

COWS is the standard validated tool used clinically in Australia to quantify opioid withdrawal severity. It guides the timing and dosing of buprenorphine induction.

COWS Severity:

Clinical pearl: Buprenorphine induction is typically begun when COWS ≥8-10 (some protocols use ≥13 for moderate-to-severe withdrawal). Starting too early - before adequate withdrawal - risks precipitated withdrawal because buprenorphine's high receptor affinity displaces any remaining full agonist.

Signs and Symptoms of Opioid Withdrawal (Mnemonic: SLUDGE reversed + autonomic excess)

• Early (6-24 h after last short-acting opioid; 24-72 h for methadone): anxiety, craving, yawning, lacrimation, rhinorrhoea, diaphoresis, mydriasis
• Later: piloerection ("cold turkey"), myalgias, arthralgia, nausea, vomiting, diarrhoea, abdominal cramps, tachycardia, hypertension, insomnia

Signs of Active Opioid Intoxication / Overdose

• Classic triad: miosis, reduced consciousness, respiratory depression
• Additional: bradycardia, hypotension, hypothermia, cyanosis

Investigation / Monitoring

Initial Assessment for OUD

• Comprehensive history: opioid type, route, quantity, frequency, last use, prior treatment attempts, co-occurring mental health conditions
• Urine drug screen (UDS): confirms opioid class (note: fentanyl may not be detected on standard immunoassay; request specific fentanyl assay if suspected)
• Bloods: FBC, EUC, LFTs, fasting glucose, HbA1c; hepatitis B and C serology, HIV serology (particularly in PWID); syphilis serology
• ECG: baseline and ongoing monitoring if prescribing methadone (QTc prolongation risk)
• Pregnancy test in women of reproductive age - important as methadone and buprenorphine management differs in pregnancy

Monitoring on MOUD

• Methadone: ECG monitoring (especially if QTc >450 ms at baseline), LFTs, UDS; dose adjustments require careful titration
• Buprenorphine: LFTs, UDS; clinical review of COWS at induction

Management

Overview of Pharmacotherapy Options

Buprenorphine / Naloxone

Mechanism

• Buprenorphine is a partial μ-opioid receptor agonist with very high receptor affinity and slow dissociation → long duration of action (24-72 hours)
• Its partial agonism produces a ceiling effect on respiratory depression, conferring a wide safety margin compared to full agonists
• Naloxone is added in a 4:1 ratio (buprenorphine:naloxone) - when taken sublingually as intended, the naloxone has negligible bioavailability and does not interfere with the therapeutic effect; if the preparation is injected, the naloxone becomes systemically active and precipitates withdrawal, thereby discouraging misuse and diversion
• Buprenorphine also has antagonist activity at κ-receptors (contributing to its antidepressant and anti-craving effects) and acts at the nociceptin/ORL-1 receptor

Induction Protocol

Critical principle: The patient must be in sufficient withdrawal (COWS ≥8-10) before the first dose to avoid precipitated withdrawal.

1. Confirm last opioid use and time elapsed
2. Assess COWS - wait until score is adequate
3. Starting dose: 2-4 mg SL, observed; if tolerating well after 1 hour, repeat 2-4 mg
4. Day 1 total: typically 8 mg SL; can go up to 12-16 mg if needed under observation
5. Stabilisation: increase to target maintenance dose of 12-24 mg/day over 3-7 days
6. Maintenance: most patients stabilise on 16 mg/day; range 8-24 mg/day

Special induction considerations: - Methadone-maintained patients: risk of precipitated withdrawal persists for up to 72 hours after last methadone dose due to its very long half-life - seek addiction medicine specialist input before inducting - Fentanyl-dependent patients: fentanyl's high receptor affinity and lipophilicity can make standard induction challenging ("low-dose" or "micro-induction" approaches may be used under specialist guidance) - In the Emergency Department: ED-initiated buprenorphine for OUD with warm handoff to community prescriber is evidence-based and should be offered at every opportunity

Prescribing in Australia

• Buprenorphine/naloxone is PBS-listed and can be prescribed by GPs (without specific waiver, unlike in the USA) but must comply with relevant state/territory regulations and typically requires an authority prescription for ongoing supply
• Supervised consumption (at pharmacy) is required initially; increasing takeaway doses as trust and stability are established

Methadone

Mechanism

• Full μ-opioid receptor agonist with a long and variable half-life (24-36 hours, up to 150 hours)
• Also blocks NMDA receptors (relevant for pain management)
• Suppresses withdrawal and craving; blocks euphoric effects of additional opioid use at adequate doses

Dosing

• Induction: 10-20 mg orally on day 1, titrated slowly (increases of 5-10 mg every 3-7 days)
• Therapeutic dose: typically 60-120 mg/day; outcomes improve significantly above 60 mg/day
• Must be dispensed as a liquid oral formulation (to prevent injection)

Key Restrictions (Australia)

• Methadone for OUD can only be prescribed by authorised prescribers (those holding a relevant state/territory permit/authority) and must be dispensed through a licensed Opioid Treatment Program (OTP) or approved pharmacy
• This is unlike buprenorphine/naloxone, which can be more broadly prescribed

Safety Concerns

• QTc prolongation: risk of torsades de pointes; ECG monitoring is mandatory
• Caution if baseline $QTc > 450\,\text{ms}$; avoid if $QTc > 500\,\text{ms}$ without specialist review
• Drug interactions: methadone is metabolised via CYP3A4 and CYP2D6 - many antiretrovirals, antibiotics (rifampicin), and anticonvulsants (carbamazepine, phenytoin) reduce methadone levels → precipitate withdrawal; inhibitors raise methadone levels → toxicity risk
• Narrow therapeutic window with greater overdose risk than buprenorphine

Naloxone - Overdose Reversal

Mechanism

• Pure competitive opioid antagonist at all opioid receptor subtypes
• Rapidly displaces opioids from receptors → reverses respiratory depression, sedation, miosis
• Short half-life: 30-90 minutes - significantly shorter than most opioids

Clinical Use: Opioid Overdose

1. Call for help; activate emergency response
2. Position: recovery position if breathing; resuscitation position if apnoeic
3. Airway: open and clear; bag-mask ventilation if apnoeic
4. Naloxone administration:
5. IV: 0.4 mg IV, repeated every 2-3 minutes as needed; titrate to restore respiratory rate and consciousness (not to full reversal - avoid precipitating acute withdrawal)
6. IM: 0.4-2 mg IM (deltoid or anterolateral thigh) if IV access unavailable
7. Intranasal: 1.8 mg per nostril (pre-filled device, e.g. Nyxoid® 1.8 mg/0.1 mL), can repeat once; 4 mg/0.1 mL devices also available
8. Repeat dosing: due to the short naloxone half-life vs. longer opioid duration, repeat doses or an IV infusion may be required; arrange hospital observation
9. Buprenorphine overdose: because of buprenorphine's extremely high receptor affinity and slow dissociation, much larger naloxone doses (potentially ≥10 mg total) may be needed; admission is warranted for symptomatic buprenorphine overdose in opioid-naïve individuals

Community Naloxone (Take-Home Naloxone - THN)

• All people with OUD (and their household contacts and carers) should be offered take-home naloxone
• Free of charge in Australia through many PHNs, pharmacies, and health services - available without a prescription in most states/territories under a standing order or Schedule 3 listing
• Intranasal formulation is preferred for community use (no assembly required; user-friendly)
• Education: recognise overdose, call 000, administer naloxone, recovery position, rescue breathing, call again if no response

Naltrexone

• Extended-release injectable naltrexone (Vivitrol®): monthly IM; useful for highly motivated patients who have completed detox; prevents relapse by blocking opioid euphoria
• Oral naltrexone: 50 mg daily; compliance is the major limitation
• Contraindications: active opioid use (precipitates severe withdrawal); hepatic impairment (hepatotoxic at high doses)
• Must be opioid-free for 7-10 days (short-acting) or 10-14 days (long-acting/methadone) before starting to avoid precipitated withdrawal

Harm Reduction

Harm reduction is a central pillar of the Australian response to OUD - it does not require abstinence as a prerequisite for engagement.

Key Harm Reduction Strategies

Brief Intervention in Clinical Settings

• Every clinical contact is an opportunity for brief intervention: FRAMES approach (Feedback, Responsibility, Advice, Menu, Empathy, Self-efficacy)
• Offer MOUD, naloxone, NSP referral, and non-judgemental, trauma-informed care regardless of patient's readiness to change
• Use motivational interviewing principles - avoid confrontation; support ambivalence

Hepatitis C in PWID

• All PWID should be screened for hepatitis C (anti-HCV antibody; if positive, HCV RNA to confirm active infection)
• Direct-acting antiviral (DAA) therapy is highly effective (>95% cure rates), PBS-listed, and can be prescribed during active injecting drug use
• Screen for hepatitis B; vaccinate if non-immune

Complications & Special Considerations

Precipitated Withdrawal

• Occurs when buprenorphine (or naloxone/naltrexone) is administered while full agonist opioids are still occupying receptors
• Clinically severe: acute, distressing withdrawal onset within minutes
• Management: supportive care (antiemetics, antidiarrhoeals, non-opioid analgesia, clonidine for adrenergic symptoms, non-benzodiazepine sedation for agitation); do not administer more buprenorphine acutely

Pregnancy

• Methadone and buprenorphine monoproduct (without naloxone) are the preferred MOUD in pregnancy
• Neonatal opioid withdrawal syndrome (NOWS) is expected and manageable - do not discontinue MOUD in pregnancy (risks outweigh benefits)
• Multidisciplinary care: obstetrics, addiction medicine, neonatology, social work

Co-occurring Mental Health Disorders ("Dual Diagnosis")

• Depression, anxiety, PTSD, and personality disorders are highly prevalent in OUD
• Treat both conditions concurrently - withholding treatment of one worsens the other
• Avoid benzodiazepines where possible (high overdose risk in combination with opioids)

Blood-Borne Virus Transmission

• Hepatitis C is endemic in PWID populations; screen and treat
• HIV risk requires ongoing education, NSP access, and pre-exposure prophylaxis (PrEP) consideration

Opioid Overdose Risk: High-Risk Periods

• After release from prison or inpatient detox - tolerance dramatically reduced; overdose risk highest
• After a period of abstinence or dose reduction
• Ensure naloxone supplied and overdose education reinforced at every such transition point

Long-Term Care and Recovery

• OUD is a chronic relapsing condition - relapse is part of the natural history, not a treatment failure
• Long-term MOUD is associated with reduced mortality, reduced illicit opioid use, improved social functioning, and reduced blood-borne virus transmission
• Regular review: dose optimisation, UDS, mental health screening, physical health monitoring (BBVs, dental, cardiovascular)
• Psychosocial support complements pharmacotherapy: counselling, peer support, housing, employment, family engagement
• Graduated takeaway doses of buprenorphine/naloxone reward stability and improve quality of life
• Goal setting should be patient-centred: for some, abstinence is the goal; for others, stability and harm reduction are equally valid and worthy outcomes
• Cultural safety is non-negotiable, particularly for Aboriginal and Torres Strait Islander patients - involve community health workers and follow culturally appropriate care frameworks