Opioid Use Disorder - Assessment, Pharmacotherapy, and Harm Reduction

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:
   • 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)
   • IM: 0.4-2 mg IM (deltoid or anterolateral thigh) if IV access unavailable
   • 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
5. 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
6. 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