Lucan · Conditions

Opioid prescribing in chronic pain

Australian guidance: RACGP Prescribing Drugs of Dependence + eTG Pain

1. Definition and epidemiology

Chronic non-cancer pain (CNCP) is pain persisting beyond the expected healing time, typically defined as pain present for more than three months, that is not attributable to malignant disease. In Australia, approximately three million people received at least one Pharmaceutical Benefits Scheme (PBS) listed opioid analgesic between April 2013 and March 2014, of whom around 150,000 patients (5%) accounted for 61% of opioid supply by defined daily doses (DDDs). Non-medical use of pharmaceutical opioids, while relatively low in Australia, doubled from 0.2% to 0.4% of the general population between 2007 and 2010, with opioid-related accidental deaths rising 61% from 705 in 2004 to 1137 in 2014.

2. Pathophysiology

Opioids produce analgesia primarily through agonism at mu opioid receptors (MOR), which are G-protein coupled receptors widely expressed in the dorsal horn of the spinal cord, periaqueductal grey, thalamus, and peripheral nociceptors. MOR activation inhibits adenylyl cyclase, reduces intracellular cyclic AMP, opens inwardly rectifying potassium channels, and closes voltage-gated calcium channels. The net effect is hyperpolarisation of nociceptive neurones and reduced neurotransmitter release, interrupting afferent pain signalling. Kappa and delta receptors contribute additional analgesia and modulate mood. With repeated exposure, receptor internalisation, downregulation, and uncoupling from G-proteins underlie tolerance. Opioid-induced hyperalgesia (OIH) is a paradoxical phenomenon in which sustained opioid exposure amplifies central sensitisation, with activation of NMDA receptors and upregulation of pro-nociceptive pathways, resulting in increased pain sensitivity that is clinically distinct from tolerance. Dependence involves neuroadaptation such that abrupt cessation unmasks a withdrawal syndrome mediated by locus coeruleus hyperactivity.

3. Clinical presentation and diagnostic criteria

CNCP presents with pain lasting more than three months that significantly impairs function, sleep, mood, or quality of life. Assessment requires a comprehensive biopsychosocial history covering pain location, quality, temporal pattern, aggravating and relieving factors, prior treatments, and the impact of pain on occupation, relationships, and mood. Examination should identify the likely pain mechanism (nociceptive, neuropathic, nociplastic) and any red flag features warranting urgent investigation. Risk stratification for opioid therapy requires screening for prior or current substance use disorder (SUD), psychiatric comorbidities, younger age (under 35 years), concurrent benzodiazepine use, and socioenvironmental instability. The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria for opioid use disorder require at least two of eleven features within a 12-month period, including craving, loss of control, and continued use despite harm. The Pain, Enjoyment, General activity (PEG) tool provides a validated three-item patient-reported measure for tracking ongoing opioid therapy response.

4. Investigations and AU-specific cutoffs

Initial assessment should include a thorough pain history and targeted physical examination to establish a diagnosis before commencing opioids. Investigations are directed by the underlying pain aetiology rather than a fixed protocol. A urine drug screen (UDS) should be considered in patients at elevated risk of problematic use; routine immunoassay screens may not detect oxycodone, methadone, or fentanyl, so specific testing must be requested if these agents are suspected. Real-time prescription monitoring (RTPM) data should be checked in all states and territories to identify concurrent Schedule 8 (S8) prescriptions, particularly benzodiazepines, which substantially increase overdose risk. The RACGP Part C1 guide defines a high-dose threshold as an oral morphine equivalent daily dose (OMEDD) exceeding 200 mg, above which mortality risk is three times higher than for doses below 20 mg OMEDD. Renal and hepatic function should be assessed before initiation and periodically during treatment, as reduced clearance elevates toxicity risk across most opioid agents.

5. Management

Management of CNCP follows a biopsychosocial framework in which opioids occupy a limited role. Non-pharmacological interventions including cognitive behavioural therapy (CBT), graded exercise, physiotherapy, and multidisciplinary pain programmes should be considered as first-line or concurrent treatments. Opioids should only be offered after non-opioid analgesics and non-pharmacological therapies have failed, are likely to fail, or are contraindicated. When a therapeutic trial is warranted, the RACGP recommends prescribing at the lowest effective dose for the shortest clinical timeframe, with a management plan developed through shared decision making (SDM) and documented treatment goals. Opioids should be prescribed from one practice and preferably one general practitioner (GP), dispensed from one pharmacy, and where appropriate dispensed in staged or supervised quantities to reduce misuse risk. Long-term opioid therapy should prompt regular reassessment of function and harms, with active attempts at dose reduction scheduled. Patients with comorbid alcohol or SUD, active psychiatric illness, or polydrug use require specialist co-management or referral and should generally not be managed with opioids in primary care alone. When problematic use is identified, opioid replacement therapy (ORT) using buprenorphine or methadone is effective and within the scope of most Australian GPs, subject to state-specific authority requirements.

6. Pharmacology and AU PBS notes

Opioids are classified as full agonists (morphine, oxycodone, fentanyl, hydromorphone, methadone, codeine, tramadol, tapentadol) or partial agonists/mixed agents (buprenorphine, which has a ceiling effect on respiratory depression). All Schedule 8 (S8) opioids require compliance with state and territory legislative authority requirements in addition to PBS rules.

Under PBS restricted benefit provisions, increased quantities or repeats for S8 opioids require authority for chronic severe disabling pain associated with proven malignancy, or chronic severe disabling pain not responding to non-narcotic analgesics where total narcotic analgesic treatment is less than 12 months. Beyond 12 months, a further authority requires review by a second medical practitioner confirming ongoing clinical need. PBS authority applications for S8 opioids are generally issued for 14 to 28 tablets, with telephone authority permitting one month supply (1800 888 333) and written application permitting up to three months supply.

Approximate oral morphine equivalent doses and key AU agents:

Morphine (MS Contin, Kapanol) is the reference opioid. Oxycodone (Endone immediate release, OxyContin controlled release) is the second most commonly used opioid in Australia since 2013. Fentanyl transdermal patches are indicated where oral dosing is impractical; 25 micrograms per hour approximates 60 mg morphine per 24 hours orally. Buprenorphine sublingual (Subutex) and buprenorphine-naloxone (Suboxone) are PBS-listed for opioid dependence treatment. Methadone liquid is used in ORT programs with supervised dispensing requirements. Codeine was up-scheduled to Schedule 4 in 2018, removing over-the-counter access. Tramadol carries serotonin syndrome risk with concomitant serotonergic drugs. Tapentadol has dual MOR agonism and noradrenaline reuptake inhibition and may cause less gastrointestinal adverse effects than morphine.

7. Complications and monitoring

Key complications include respiratory depression (risk amplified by concurrent benzodiazepines, sedatives, alcohol, sleep apnoea, and high dose), constipation (opioid-induced bowel dysfunction), sedation and cognitive impairment, falls in older patients, opioid-induced hyperalgesia (OIH), endocrine suppression (hypogonadism, adrenal insufficiency with long-term use), and opioid use disorder (OUD). Fatal overdose risk triples at OMEDD above 200 mg compared with doses below 20 mg and is further amplified by concurrent benzodiazepines, slow-release formulations, older age, renal or hepatic impairment, pregnancy, and comorbid psychiatric illness.

Monitoring schedule for established opioid therapy should include:

Review at 2 to 4 weeks after initiation to assess efficacy, function, and adverse effects. At each review, assess pain scores, functional status (PEG tool or equivalent), aberrant drug-related behaviours, and whether ongoing opioid therapy remains justified. Periodic UDS in higher-risk patients. Annual comprehensive review including reassessment of diagnosis, dose minimisation, consideration of opioid rotation or tapering, and documented rationale for continuation. RTPM check at each S8 opioid prescription. Naloxone rescue prescription should be considered and offered to patients at elevated overdose risk, their carers, and household members, consistent with national harm-reduction guidance.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.