Evidence-based guidance for opioids in acute and chronic pain

As with any treatment, prescription of opioids should be based on:

• a comprehensive medical assessment
• a diagnosis
• consideration of the likely risks and benefits of any medication, as well as alternative interventions
• a management plan derived through shared decision making (SDM) and continual clinical monitoring.

Opioid treatment seeks to maximise outcomes for the health and social functioning of the patient while minimising risks. To minimise risks, opioids should be prescribed at the lowest effective dose for the shortest clinical timeframe.

Accountable prescribing also involves an assessment of patient risk stratification, provision of adequate therapeutic monitoring, dose limitations and compliance with national and state law.

As a general precaution, GPs should avoid prescribing opioids to patients with comorbid alcohol or substance use disorders (SUDs) or polydrug use. Patients who use two or more psychoactive drugs in combination (polydrug use) and those with a history of substance misuse may be more vulnerable to major harms. GPs should consider seeking specialist opinion in the management of these patients.

When opioid medications are prescribed for treatment of acute pain, they are often prescribed in addition to paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs)

Evidence into practice - Acute pain

Background to managing acute pain in general practice

Acute pain is an unpleasant sensory and emotional experience usually related to surgery, injury or disease. It is associated with actual or potential tissue damage to non-neural tissue and is experienced due to activation of nociceptors. This is also known as nociceptive pain.

Acute pain includes inflammatory pain; that is, pain that occurs in response to tissue injury and the subsequent inflammatory response. Typically, inflammatory pain disappears after resolution of the initial tissue injury. However, in chronic disorders (eg rheumatoid arthritis) the pain may persist for as long as inflammation is active.

Effective management of acute pain requires tailoring treatment to the individual patient; awareness of the science behind contextual and placebo effects; competence with multimodal analgesia (ie the concurrent use of different classes of analgesics); and providing patient reassurance and education, including expected duration of pain episode and warning signs that would require immediate medical attention.

In managing acute pain, GPs should:

• undertake a complete biopsychosocial assessment of the patient with pain
• be familiar with the evidence for selected acute pain presentations in general practice and conditions where opioids are not routinely recommended
• prescribe opioid medications only for the treatment of acute nociceptive pain when non-opioid pain medications and therapies have failed or are likely to fail
• undertake a patient selection/exclusion process before commencing opioids.

If opioids are commenced for the pain of acute nociception, there is a need to give clear direction about the anticipated duration of therapy. Usually three days or less of opioid therapy will be sufficient for non-traumatic pain not related to major surgery. Typically, opioids should be weaned and ceased as the acute injury heals. Even in complex post-surgical cases this should be within 90 days.⁵

For a review of all acute pain issues, GPs are advised to review the evidence collated by ANZCA’s Faculty of Pain Medicine.

Minor analgesic for pain

GPs should prioritise non-opioid therapies for initial pain management or for the patient being assessed and managed in a general practice. GPs should be familiar with the evidence for selected acute pain presentations in general practice and conditions where opioids are not routinely recommended (Table 1).

In managing acute pain presentations:

• paracetamol by itself is no longer first-line treatment for most mild to moderate acute pain because of lack of clinical effect^9–11 and possible superiority of non-steroidal anti-inflammatory drugs (NSAIDs)¹²
• ibuprofen and naproxen are appropriate first-line NSAIDs for mild to moderate acute pain (based on effectiveness,¹¹ adverse effect profile,13 cost and over-the-counter [OTC] availability)
• non-selective NSAIDs given in addition to paracetamol improve analgesia compared with either medicine given alone, in particular ibuprofen combined with paracetamol^14,15
• paracetamol or NSAIDs combined with codeine (at a dose above 60 mg) provide clinically important pain relief in the immediate term¹⁶
• cyclooxygenase-2 (COX-2) selective NSAIDs are second-line medications for mild to moderate pain based on their similar effectiveness to non-selective NSAIDs.¹⁷

Table 1

Acute pain conditions where opioid medications are not recommended ^18,19

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Table 1. Acute pain conditions where opioid medications are not recommended ^18,19

Patient selection/exclusion process for opioid  therapy

Opioid medications should only be used for the treatment of acute pain when non-opioid pain medications and therapies have failed or are likely to fail to provide adequate pain relief, or other contraindications exist.

There are several patient groups in which caution is advised before commencing opioid therapy (refer to Table 2). GPs are advised to be familiar with prescribing precautions in these groups. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids.⁸ The number of doses dispensed should be no more than the number needed (and should not be pro re nata [PRN]). This should be based on the expected duration of pain severe enough to justify prescribing opioids for that condition.

Usually three days or less of opioid therapy will be sufficient for non-traumatic pain not related to major surgery. Continuing requirements for opioid therapy after this time should prompt review. Long-term and problematic opioid use, including sharing with others, often has its origins in the acute pain setting. Clinical discipline is needed to restrict opioid use to time periods and conditions for which it is beneficial.

Table 2

Patient groups that require caution when considering opioid therapy²⁰

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Table 2. Patient groups that require caution when considering opioid therapy²⁰

Migraine

Patients who experience mild migraine-related headache and disability may be effectively treated with simple analgesics, either alone or in combination with an antiemetic. Paracetamol,⁵¹ aspirin,⁵² ibuprofen⁵³ and diclofenac⁵⁴ have all shown benefit. Appropriate antiemetics include (parenteral) metoclopramide⁵⁵ and prochlorperazine.^56,57

Triptans or IV ketorolac⁵⁸ may be particularly effective in the presence of severe pain and disability where simple analgesia has failed to provide adequate relief in the past.⁵⁹

Opioids are of limited benefit in the treatment of migraine and are not recommended.⁶⁰ Opioid use for migraine is associated with more severe headache-related disability, symptomology, comorbidities (depression, anxiety and cardiovascular disease and events), and greater healthcare utilisation.⁶¹ However, opioids may be considered as a last resort when other migraine treatments are contraindicated.⁶²

Cluster headaches

Cluster headache is a rare primary headache disorder, presenting predominantly in males,^63–65 with recurrent acute episodes of brief severe unilateral periorbital pain. Guidelines for the treatment of cluster headache attacks propose first-line treatments to be high-flow oxygen (eg 100% oxygen at 6–12 L/min)^66–69 and tryptans (eg sumatriptan 6 mg subcutaneously, zolmitriptan 5 mg and 10 mg intranasally).^70,71

Temporomandibular dysfunction

Headache or facial pain attributed to the temporomandibular joint is often associated with tension headache⁷² and cervical spine dysfunction.⁷³ Teeth grinding (bruxism) is a common contributor. The most effective therapies include interocclusal appliance therapy.⁷⁴ There is limited evidence for the successful pharmacological management of temporomandibular dysfunction (TMD) pain.⁷⁵ If a medication is going to be used, the best evidence exists for naproxen (1000 mg/day), which is more effective than celecoxib (200 mg/day) and placebo.⁷⁶

Evidence into practice – Chronic pain

Chronic pain has been historically defined as continuous or recurrent pain that persists for an extended period (generally more than three months). However, the biological mechanisms for chronic pain are quite different from those of acute nociception, and should not be considered as ‘unhealed’ acute pain. CNCP is a collection of clinical conditions with involvement of single or multiple pathophysiological mechanisms leading to persistent pain. It is also an individual, multifactorial experience influenced by culture, previous pain events, beliefs, expectations, mood and resilience.

Due to methodological weaknesses of chronic pain studies, interpretation and translation of evidence into practice is difficult. There is limited evidence to determine long-term benefits (outside of end-of-life care); however, there is evidence of risk of harm that increases with dose. While guidelines suggest opioids in the management of some chronic pain conditions, they are not recommended for routine or first-line use. In managing CNCP, GPs should:

• undertake a complete biopsychosocial assessment of the patient with pain
• optimise non-drug therapies, and optimise non-opioid therapies as the primary interventions of care.

Opioids for CNCP should be reserved for selected patients with moderate or severe pain that significantly affects function or quality of life and which has not responded to other therapies. If primary interventions fail or are suboptimal, opioid therapies may be considered. GPs should share the decision-making process with the patient, and if opioid therapy is considered, there should be:

• a patient selection/exclusion process before a therapeutic opioid trial
• formal care planning based on specific goals and risks
• an opioid trial, which is undertaken to determine a patient’s response to opioid therapy. This trial includes the selection of an appropriate opioid, formal measures of analgesia and functionality, a trial of dose reduction, and a drug cessation plan if the trial fails
• an ongoing assessment and evaluation by the accountable prescriber if the trial shows opioid benefit
• opioid tapering and cessation if suboptimal results or aberrant behaviour occurs.

Long-term use should be uncommon, undertaken with caution and based on consideration of the likely risks and benefits of opioids. Intermittent use is preferable.

GPs should also be aware of chronic pain conditions where there are known clinical complexities involving opioids. These complex clinical areas include the exacerbation or new acute pain in patients on long-term opioid therapy, managing opioids after a non-fatal overdose, and managing the inherited patient.

Some patients on long-term treatment with opioids in CNCP may represent de facto maintenance treatment for iatrogenic opioid dependence. GPs should aim to taper patients taking >100 mg oral morphine equivalent (OME) per day.

Assessment of patients with chronic non-cancer pain

The foundation of care for CNCP is a comprehensive biopsychosocial assessment, and a complete documentation of the patient’s pain condition, general medical condition and psychosocial history, psychiatric status, and substance use history.^77,78 A biopsychosocial assessment completes a more complex understanding of the patient’s pain perspective. Factors do not always neatly fit into one category; for example, depression may have physical and social aspects as well as being a psychological factor influencing pain.

A comprehensive pain assessment includes a:

• general assessment and pain specific history (that explores the pain type, severity, functional impact, context, and the patient’s meaning of pain, expectations and fears)
• physical examination (assessing for signs of tissue damage or disease that might indicate nociceptive and/or neuropathic mechanisms of pain)
• psychological assessment (the pain experience is affected by mood, stress, coping skills, fear avoidance, and catastrophising).

Non-drug therapies for chronic pain

Before any therapies are undertaken, GPs are advised to consider the science and evidence of contextual and placebo effects in pain management. The manner in which a clinician explains and delivers therapy has an impact on outcome.⁷⁹ Practitioners who master not only the disease and treatment, but also cultivate a therapeutic relationship may be more effective at pain management.⁸⁰

The basis for pain management is a strong continuous therapeutic doctor–patient relationship.

Management should optimise general health, including addressing comorbid physical and mental health conditions. GPs should provide adequate patient education about the causes of chronic pain. Further information regarding neuroscience education can be found here.

GPs should engage in a frank discussion and negotiation about different pain strategies and the goals of treatment. These goals should go beyond pain relief alone (eg improvement in physical, social, emotional and mental functioning, including an increase in activity) and there should be an agreement that if the goals are not met, then the treatment will be discontinued.

Non-drug and non-opioid pharmacological therapies are preferred options for management of CNCP.⁸ Multimodal interventions are effective.⁸¹ Exercise,^82–86 selective psychological interventions,^87,88 social interventions, and nonopioid therapies are all advocated.

Most patients with chronic pain are physically deconditioned from inactivity.⁸⁹ Movement and exercise therapies, regardless of their form, are recommended in the management of patients with chronic pain.⁸⁶ Physiotherapists and exercise physiologists with an interest in chronic pain are advocated. Further information on the effectiveness of movement and exercise interventions can be found here.

Psychological approaches aim to increase self-management, behavioural change, and cognitive change rather than directly eliminate the locus of pain. Psychologist intervention is advocated for assessment and management of selected presentations. Further information on the effectiveness of psychological interventions can be found here.

Non-opioid medication for chronic pain

Effective management requires knowledge of the frameworks for pain, different treatment approaches, and an individualised multifaceted intervention plan for the patient^{5,78,86,89–93} depending on specific contributors of pain.

Where analgesics are considered appropriate, the optimal approach to manage chronic pain is without opioids, prioritising use of minor analgesics and analgesic adjuvants (eg antidepressants, anticonvulsants) instead.^5,8 ‘Adjuvants’ refers to medications that are co-administered with analgesics to enhance pain relief via other pathways. The evidence for effectiveness of adjuvants varies for pains with different nociceptive, neuropathic and nociplastic origins. A brief overview of the evidence can be found here.

In countries where they are available, cannabinoids may have a place in relieving chronic neuropathic pain.^94,95

However, the evidence for effectiveness is considered weak and their role is being debated in Australia.^96,97

GPs should prescribe one analgesic/adjuvant drug at a time and monitor individual responses. While it is accepted practice to run a clinical trial over several weeks, many of the agents will elicit an analgesic response within the first two weeks of treatment (if achieved, the response tends to last).^98–100 If functionally meaningful benefit does not ensue, stop the drug and try an alternative. Because of individual variation in pain, patients may respond to one drug within a class, but not to others (eg a patient may respond to naproxen, but not ibuprofen). Therapy failure due to inadequate relief or side effects should not stop doctors from trialling alternative medications from the same class (eg NSAIDs, anti-epileptics). Combination adjuvants (anticonvulsants and antidepressants) are common but inadequately studied.

For patients who achieve clinically meaningful analgesia, use the lowest individualised effective dose to minimise adverse effects. Reassess regularly (eg every two weeks), and trial medication withdrawal to determine that the response is due to the drug and not natural history. It is recognised that patients treated with a placebo can also improve over time.¹⁰⁰

Patient selection/exclusion process before an opioid trial

If alternatives to opioid treatment fail, have limited benefit or are inappropriate, a supervised opioid trial may be initiated. Opioids for CNCP should be reserved for select patients with moderate or severe pain that significantly affects function or quality of life and that has not responded to other therapies.

Prescription of opioids, as with any treatment, should be based on a comprehensive medical assessment; a diagnosis; thoughtful consideration of the likely risks and benefits of any medication, as well as alternative interventions; and a management plan derived through SDM and continual clinical monitoring.

In selecting or excluding patients before starting opioid therapy, GPs should:

• be aware of the limitations of opioids in managing some pain syndromes (eg functional visceral pain, such as irritable bowel syndrome and bladder pain syndrome, is not sensitive to opioids)
• be aware of patient groups or contexts requiring additional caution or exclusion. Additional advice needs to be considered when patient selection for opioid therapy involves pregnancy, workers’ compensation injuries, patients who drive, patients with sleep apnoea and disordered breathing, patients aged 65 or older, patients with renal disease, patients with hepatic disease, culturally and linguistically diverse patients, and patients with mental health conditions
• evaluate risk factors for opioid-related harms in individual patients, including review of the patient’s history of controlled substance prescriptions using the Prescription Shopping Programme (PSP) or state PDMP data to determine whether the patient is receiving opioid dosages or dangerous combinations (especially benzodiazepines¹⁰¹) that put him or her at high risk for overdose
• avoid prescribing opioids to patients with polydrug use, comorbid alcohol or substance use disorders. GPs should consider tapering benzodiazepines and seeking specialist opinion or a specialised pain management facility⁹⁰ in the management of these patients.

Care planning for an opioid trial

The aim of an opioid trial is to discover the individual’s responsiveness to opioid therapy in terms of decreased pain, increased function and improved quality of life. Before starting opioid therapy for chronic pain, GPs should:

• ensure patients are aware of known risks and realistic benefits of opioid therapy, and of their responsibilities for managing therapy (including risks to other individuals if opioids are intentionally or unintentionally shared) • establish treatment goals with all patients, including realistic goals for pain and function, and consider how opioid therapy will be discontinued if goals are not met or benefits do not outweigh risks^8,92
• consider a UDT to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs.

Care plans should incorporate strategies to mitigate risk including having only one prescriber for ongoing analgesics;^5,91 offering naloxone when factors that increase risk for opioid overdose are present (eg history of overdose or substance use disorder, higher opioid dosages or concurrent benzodiazepine use); and sharing care for high-risk patients with clinical specialists.⁸

While screening for opioid risk, treatment agreements⁸⁹ and urine testing^{5,78,92,93,102} are often advocated, they have not been shown to reduce overall rates of opioid prescribing, misuse, or overdose.^5,103 Patient treatment agreements do serve an administrative role, clarify expectations and behaviour standards, and have educational purposes.^104,105 GPs should use their discretion when considering candidates for a urine drug screen (UDS) and treatment agreements.

It is important to have an ‘exit strategy’ if the trial fails to achieve agreed outcomes. The strategy should preserve the therapeutic relationship while also managing possible misuse of opioids.

Undertaking an opioid trial

Opioids for CNCP should be reserved for select patients with moderate or severe pain that significantly affects function or quality of life and that has not responded to other therapies. An opioid trial should occur in conjunction with formal measures of analgesia and functionality. Validated brief assessment tools that measure pain and function (eg Pain, Enjoyment, General activity [PEG]¹⁰⁹ in Appendix E) or other validated assessment tools may be helpful and time effective.

When trialling opioids for chronic pain, opioid selection should be based on evidence of safety and benefit for the pain type and patient factors. The opioid should be in addition to appropriate non-drug therapy and non-opioid drug therapies.

Unless clinically contraindicated, consider selecting an effective opioid with less potential for harm such as oral tapentadol, transdermal buprenorphine or oral tramadol.^8,78 Start opioids at a low dosage, increase gradually (refer to individual opioids) and monitor opioid effectiveness using the 5As of chronic pain management and the PEG tool until optimal dose is attained.^8,78,101

Patients likely to benefit from opioids in the long term will demonstrate a favourable response within 2–4 weeks of initiating therapy. It is accepted practice to run a clinical trial over 8–12 weeks to allow for normal variations of life. An important part of any trial is to reduce opioid doses to establish minimal needs.

Patients who do not experience clinically meaningful pain relief early in treatment (ie within three months) are unlikely to experience pain relief with longer-term use.¹¹⁰ Suboptimal therapeutic response may be due to failure to recognise psychosocial aspects of the patient’s pain.

If the initial choice of opioid is ineffective, or if adverse effects are unacceptable, opioid rotation may be tried. In clinical practice, opioid rotation must be performed with consideration of individual patient characteristics, comorbidities (eg concurrent psychiatric, pulmonary, renal, or hepatic illness), and concurrent medications.¹¹¹ Reduce the starting dose of the new opioid by 50% of the calculated equianalgesic dose of the first opioid. This reduction in dose may result in improved tolerability while incomplete cross-tolerance may result in equivalent efficacy.

To minimise risks, opioids should be prescribed at the lowest effective dose for the shortest clinical timeframe. Caution should be used when increasing dose from low to moderate (ie above 40–50 mg per day OME).⁸ While there is no international consensus on a maximum (ceiling) dose,^5,112 a ceiling of 100 mg per day OME is recommended for Australian GP prescribing.^5,8,92 Above this dose, specialist review is advocated.⁹²

Ongoing therapy, assessment and monitoring

Long-term opioid use should be uncommon, undertaken with caution and based on thoughtful consideration of the likely risks and benefits of opioids. If opioids provide benefit (pain relief and improved functioning), opioid analgesia can be an acceptable long-term therapeutic option.

GPs should continually evaluate treatment efficacy and harms, and monitor for known comorbidities. Patients should be re-evaluated at least every three months, and within four weeks of any dose escalation.⁸

Although the evidence for use of instruments to assess patient-reported safety, efficacy, or misuse of current opioid therapy for chronic pain is lacking,¹¹³ it is advised that patients are evaluated using the 5As of chronic pain management.^8,114 Only continue opioid therapy if there is documented clinically meaningful improvement in pain and function that outweighs risks to patient safety.^5,8,78,101

While baseline UDTs are recommended,^{5,78,92,93,102} prescribers can use discretion for ongoing testing according to patient risk. Consider UDTs at initiation and then at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs.^8,92 When using UDTs be aware of benefits and limitations, appropriate test ordering and interpretation, and have a plan to use results.⁹²

In all states except NSW, GPs should also seek state regulatory authorisation for any patient who has been prescribed Schedule 8 (S8) opioids for two months or longer.¹¹⁵ In NSW, only certain oral opioids (buprenorphine, hydromorphone and methadone) require an authority.

Pharmaceutical Benefits Scheme (PBS) regulations dictate an independent opioid prescribing review at 12 months of therapy. The RACGP recommends a structured review using a checklist for this purpose.

Long-term opioid prescriptions should be at the lowest effective dose, and regular attempts at reduction should be scheduled.¹⁰³ Intermittent use has also been advocated.¹⁰³ Proper management of opioids in well-selected patients with no history of SUD can lead to long-term (≥26 weeks) pain relief for about 25% of patients.^116,117 Continued professional monitoring of health outcomes is required.

Where continued opioid therapy is inappropriate due to failure of benefits to outweigh harms, or if there is evidence of problematic use (eg rapid dose escalation), work with patients to taper and discontinue opioids.^8,90,101 This involves preserving the therapeutic relationship, optimising non-opioid therapies, and working with patients to taper opioids to lower dosages or to discontinue opioids.^5,90 Patients have the right to respectful care that promotes their dignity, privacy and safety; abruptly discontinuing opioid treatment without offering a feasible plan for tapering treatment could be considered a failure of duty of care.

GPs should regularly assess whether the patient satisfies individual state health legal definitions of drug dependence and seek advice from the state regulatory authorities if issues arise. All states and territories run drug and alcohol advisory services, which offer information, advice, referral, intake, assessment and support 24 hours a day. They offer services for individuals, their family and friends, GPs, and other health professionals.

Chronic post-surgical pain

Management of chronic post-surgical pain

CPSP is defined as pain developing and persisting beyond the time expected for the normal healing process (ie persisting for at least two months). CPSP can affect 15–60% of all surgical patients.¹¹⁸ The incidence of CPSP varies with the type of operation and it is more common where nerve trauma is inevitable (eg amputation) or where the surgical field is richly innervated (eg chest wall).^119–121 For example, following:

• inguinal hernia repair or caesarean section, 10% of patients report ongoing pain and disabilities six months after surgery
• mastectomy or lumpectomy, 20–30% of women report chronic pain
• amputation, thoracotomy or coronary bypass surgery, 30–50% of patients report persistent pain.¹²²

Depending on the type of surgery, CPSP is often neuropathic pain (on average one-third of cases; range from 6% to 54%). Pain involving such a neuropathic component is usually more severe than nociceptive pain and often affects the quality of life more adversely.¹²³

Nociceptive and neuropathic processes in the periphery (including nerve injury) and neuroplastic processes (leading to peripheral and central sensitisation) are all implicated in the transition from acute to chronic pain. The relative degree of ongoing inflammation or intraoperative nerve injury resulting in peripheral and central sensitisation may explain the variation in risk and, to an extent, the characteristics of CPSP for different operations. In addition to the type of surgery, the development of CPSP is influenced by patient factors including:

• psychological factors such as anxiety, depression, stress, fear of surgery, hypervigilance and pain catastrophising^124,125
• demographic factors, such as younger age for adults and female gender
• genetic and epigenetic factors, which influence both the sensitivity of individuals to analgesics and their risk of CPSP.126,127

All practitioners should aim to prevent the progression of acute to chronic pain. Treatments that address nociceptive and neuropathic pain should be considered, including opioids where appropriate.

Pregabalin and gabapentin may have a role in preventing CPSP due to their effect on neuropathic pain. However, considerable uncertainty exists regarding efficacy with limited and contradictory evidence.⁷

Chronic visceral pain

Visceral pain refers to pain in the trunk and abdominal areas of the body that includes the heart, lungs, abdominal and pelvic organs. Examples of chronic visceral pain include chronic chest pain, chronic pancreatitis, and chronic pelvic pain.

Visceral pain is diffused and can be difficult to localise.¹²⁸ It may be accompanied by nausea, vomiting and changes in vital signs. Treatment goals are both causal and symptomatic and involve holistic strategies including patient education.¹²⁹

Fibromyalgia

Fibromyalgia is a common and potentially disabling condition affecting 2% of the population in developed countries, predominantly young to middle-aged women.¹³⁰ Fibromyalgia has a varied and fluctuating clinical spectrum. Cardinal features include widespread musculoskeletal pain and tenderness; poor quality, unrefreshing sleep; significant levels of fatigue; cognitive disturbances, particularly problems with concentration and memory; and high distress levels.¹³¹

Fibromyalgia pain is considered to be due to central sensitisation.¹³² Exercise remains the strongest therapeutic recommendation.¹³³ Specific guideline recommendations should be consulted prior to therapies.^134–137

Complex regional pain syndromes

Complex regional pain syndrome (CRPS) is a debilitating, painful condition in a limb associated with sensory, motor, autonomic, skin and bone abnormalities. Pain is typically the leading symptom, but it is often associated with limb dysfunction and psychological distress.¹³⁸ There is usually a history of precipitating event or injury; however, the severity of the clinical pain presentation is often disproportionate to the severity of the inciting event.

Exact mechanisms for the pathogenesis of CRPS are not understood.^139–143 A combination of elements including inflammation, dysfunction within sympathetic and somatosensory nervous system, and cortical (not psychological) factors are thought to contribute to the generation and perpetuation of symptoms.¹³⁸ There is no evidence that paracetamol assists in CRPS, and insufficient evidence regarding the efficacy of NSAIDs and opioids. Although there is no evidence supporting the long-term effectiveness of anticonvulsants for CRPS, these agents may be useful in providing pain relief in the earlier stage of the disease.¹⁴⁴

GPs should seek specialist advice with presentations with CRPS.

Acute exacerbation of existing chronic pain

If patients experience an acute exacerbation of CNCP, the aetiology of the pain must be identified rather than just treating it as an acute nociceptive event. The aetiology may be multifactorial, and it is advised that the patient’s mental health status and social situation should be formally assessed to determine if additional resources may be appropriate. It may also be appropriate to check the PDMP and patient-controlled electronic medical record (if present) for history of opioid prescriptions.

The treatment for the chronic pain patient may be significantly different from the acute episode. Exacerbations of pain should be managed with non-opioid therapy: physical therapies and NSAIDs should be used for periodic flareups of mild to moderate inflammatory or non-neuropathic pain.^19,89 Because of potential risks and adverse effects, clinicians are encouraged to avoid prescribing increased dosage or additional opioids.¹⁹

New painful condition in a patient with chronic pain

As with acute exacerbation of chronic pain, in any new pain presentation it is important to identify the source of pain rather than just treating for an acute nociceptive event, avoid prescribing increased dosage or additional opioids,¹⁹ use non-opioid therapy as appropriate,⁸⁹ and assess the patient’s mental health status and social situation to determine if additional resources are required.

If a new presentation does dictate opioid treatment, consider monitoring in an appropriate care setting. Dosing opioids for acute pain in a patient already taking opioids is problematic. The patient may require a higher dose to achieve the same analgesic effect. The higher dose puts the patient at greater risk for an adverse event. Note that patients already taking opioids do not require a longer than normal course of treatment for acute pain. Once the acute event has passed, reduce opioids to maintenance levels.

Opioid withdrawal presenting as acute pain

Consider opioid withdrawal when evaluating opioid-tolerant patients who present with acute pain complaints or gastrointestinal symptoms. Opioid withdrawal can occur when patients have stopped, lost or overused their medications. Patients are often reluctant to share this information with their clinician.

Opioid withdrawal generally presents with anxiety 12 hours after the last dose, and becomes physically detectable within 24 hours after the last use of short-acting opioids and 48 hours after last use of long-acting opioids.

Unless the patient is otherwise medically unstable, withdrawal is not life threatening. However, it may be very distressing and necessitate reassurance and comfort measures. All states and territories run an alcohol and drug information service, which offers information, advice, referral, intake, assessment and support 24 hours a day.

Managing opioid therapy after non-fatal overdose

Patients who have had a presentation or admission for opioid accidental or non-accidental overdose are at significant risk for another overdose and further harms.¹⁴⁵

At two years, the cumulative incidence of repeated overdose was:¹⁴⁵

• 17% (95% confidence interval [CI]: 14%, 20%) for patients receiving high dosages of opioids after the index overdose
• 15% (CI: 10%, 21%) for those receiving moderate dosages
• 9% (CI: 6%, 14%) for those receiving low dosages
• 8% (CI: 6%, 11%) for those receiving no opioids.

Opioid discontinuation after overdose is associated with lower risk for repeated overdose.¹⁴⁵

Non-fatal opioid overdose is an opportunity to identify and treat substance use disorders, pain and mental health issues.

All patients admitted or presenting to hospital emergency departments (EDs) with non-fatal opioid overdose must have a full pain and psychiatric evaluation prior to discharge, and consideration of opioid cessation or provision of naloxone for peer or family member administration. A clear plan for opioid safety after discharge and communication with usual treating practitioners in the community is essential.

Naloxone distribution programs are firmly rooted in the principles of harm reduction. Naloxone is safe, effective, inexpensive, and relatively easy to administer via intramuscular (IM) injection.¹⁰⁶

The inherited patient – Continuation of long-term opioid management plans initiated by other healthcare providers

Overview

Patients often arrive from other practices or institutions requesting continuation of their long-term opioid management programs. These situations can produce a therapeutic dilemma for the new practitioner. Patients’ histories and management regimes may be quite complex, and some practices and institutions have prescribing practices that are variable or may not be evidence based or safe.

Patient requests for ongoing pain management may be quite legitimate, but, unfortunately, this type of presentation is also common for drug-seeking behaviour for opioids. In both situations, the patient may be physically dependent on opioids. When these patients are deprived of opioid medication, they may experience acute withdrawal.

In the inherited-patient situation, caution is advised while acknowledging the patient’s right to respectful care that promotes their dignity, privacy and safety. Patients with legitimate clinical indications for long-term opioid therapy have expressed concern regarding stigmatisation and lack of access to ongoing care. It is important GPs independently make a thorough clinical assessment of each patient’s opioid use, and develop an individual management treatment plan consistent with clinical guidelines while safeguarding against abuse and diversion. Treatment should seek to maximise health outcomes across a range of domains (eg patient pain acceptance, functionality, risk).

In the event of an SUD being detected, this plan should also include remedial programs or referral to appropriate drug misuse agencies. Practice policies should be in place to assist the management of the inherited patient using drugs of dependence.

Comprehensive clinical assessment of the inherited patient

The assessment of an inherited patient with an existing long-term opioid treatment plan includes:

• a review of the patient’s general health conditions, including any SUD (eg alcohol, benzodiazepines, opioids)
• a full social and psychological assessment
• confirmation of the pain diagnosis, which may require a formal in-depth review of the pain diagnosis including radiology, response to therapeutic interventions, and current functionality
• establishing the medical necessity and the appropriateness of prescribing regimen
  • assess the risk–benefit ratio – some existing plans may have evidence-based multimodal therapy; others may have quite high-risk or inappropriate regimes with mixed and multiple opioids, multiple psychoactive drugs or drugs that are contraindicated or not consistent with regulations
  • confirm that opioid drugs and doses are correct (ie calculate the patient’s daily morphine equivalent dose for all opioids prescribed to determine whether these dosages are safe or at increased risk)
  • determine pain and function with this level of opioids and other medications and ask ‘Is this patient at risk if I maintain the same prescription?’
• deciding whether the regimen represents rational accountable prescribing, is outside the scope of practice or the doctor, or needs optimisation
• assessing aberrant behaviours using the 5As approach
  • tolerance and physical dependence are normal consequences of sustained use of opioid analgesics and are not the same as addiction
  • patients treated for ‘legitimate’ pain may become physically dependent on the supervised therapy of opioid medications, but this does not constitute a substance use disorder.
• contacting prescription shopping services or real-time prescription monitoring services.

Prescribers should verify patient-reported treatment plans and any identified concerns about misuse or dependency with the previous prescriber and pharmacist directly.

Assessment of risk with the inherited patient

Even when a case for ongoing care is established, the general risk category of the patient should be considered and GPs are not obliged to take full responsibility for care of all patients. For each patient, the risk category is dependent on patient factors, practitioner factors and resources.

Higher-risk situations also include those where:

• staff safety may be impacted
• care is outside the expertise of the practitioner
• long-term health prospects of patients are being compromised by lack of access to state or territory facilities
• patients have serious mental illness or are taking antipsychotic medication
• patients have past family or personal history of substance misuse
• polydrug use is present
• patients have been recently discharged from a correctional services facility.

For more information about deciding when to seek advice or consider referral to a psychiatrist or pain/addiction specialist refer to Prescribing drugs of dependence in general practice, Part A.

Care planning for the inherited patient

• communicate empathically but honestly with patients about opioid use (including realistic expectations about the likely or potential outcomes of their treatment)
• develop a defensible, rational, and compassionate patient care strategy
• obtain relevant permits to prescribe opioids from the state or territory authorities.

Patients need to be informed about the purpose, importance, benefits and risks of their medicines. This enables them to engage in SDM, which has been shown to build trust, prevent harm and reduce surprise and distress if complications or adverse events occur.

Not all SDM will result in agreement. It is challenging when there is pharmacologic or other therapeutic disagreement with a patient. But there is a difference between patient-centred care and patient-controlled care. Acknowledging patient beliefs, expectations and preferences does not involve crossing professional boundaries, ignoring laws or continuing therapy that is considered detrimental to the patient’s health.

In this situation, it is necessary to maintain professional discipline and clinical honesty. If a patient refuses the advice of a GP, they should be advised about the implications of deciding not to receive the healthcare offered. The patient should be given sufficient time to consider and clarify any information in order to make an informed decision, taking into account the context of the clinical situation.¹⁴⁶

Where GPs suspect an opioid use disorder, they should be honest with the patient while reassuring them that effective treatments are available. Scripting sentences and techniques for GPs are available to assist in politely refusing to provide opioid prescriptions. Appropriate management includes the initiation of remedial programs or referral to appropriate drug misuse centres. In some states such as Victoria, South Australia (and possibly New South Wales in 2018) GPs are permitted to prescribe opioid replacement therapy (ORT). Advice from state-based drug and alcohol services is available at all times.

GPs should not evict patients from their practice because of manipulative behaviour or therapy refusal.

Using legislation to assist with challenging patients

Clinicians should not see legislation covering the prescription of controlled substances as a barrier to appropriate prescribing. Instead, legislation acts as protection for prescribers as well as for patients.

When patients make demands for opioids, practitioners can strongly state their duty to act within state, territory and national legislative frameworks, and to manage their prescribing practices within the laws and clinical and professional standards.

Practitioners should determine who is the patient’s authorised prescriber. If the prescriber is not in the state or territory where the consultation is being made, new authorisation will need to be obtained. Time for the necessary processes will need to allowed.

Using opioid rotation and rationalisation

When opioids are less effective than expected or a new patient presents with ‘irrational pharmacotherapy’, then opioid rotation, consolidation (eg using one type, longer acting) or taper (in some cases, to the point of discontinuation) should be considered.

Opioid rotation may help to:

• improve analgesia
• lower the dose of the prescribed medication
• manage loss of analgesic efficacy or the presence of toxicity.¹⁴⁷

Note that clinically, patients often show incomplete cross-tolerance when rotated from one analgesic to another.

Use urine drug testing

A baseline UDT should be performed at the initial visit, with a request to include detection of oxycodone and other drugs not usually recognised by immunoassay.

Further testing is used as clinically indicated. Unexpected results from such tests should be interpreted within their limitations: fentanyl, buprenorphine, synthetic drugs, anabolic steroids, and usually oxycodone are not routinely detected and must be requested as additional tests (at extra cost to the patient).

All state and territory health authorities have 24-hour telephone access to assist with drug and alcohol queries.

GPs can get urgent advice and support for patients on opioid therapy, and seek information on referral options or advice on issues on care coordination between multiple providers.
 

Background to opioid tapering

It is not unusual for opioid medication to become ineffective over time, or for adverse effects to develop. Where opioid trials fail to achieve agreed outcomes or harms outweigh benefits, GPs should follow their ‘exit strategy’ to taper and/or cease opioids while preserving the therapeutic relationship.

In other cases, long-term treatment with opioids in CNCP may represent de facto maintenance treatment for iatrogenic opioid dependence. Tapering should be attempted for all patients who have been on long-term opioid therapy of greater than 100 mg OME per day. Reduction in opioid dose may reduce adverse effects including cognitive impairment and the likelihood of non-fatal or fatal unintentional overdose.

In all cases, patients have the right to respectful care that promotes their dignity, privacy and safety. Ending a relationship with a patient or abruptly discontinuing opioid treatment without offering a feasible plan for tapering or addiction treatment could be considered an abrogation of the accountable prescriber’s duty. Such approaches rarely solve the problem.

Patients can experience significant improvement in pain severity, functioning, and mood when their opioid therapy is tapered to a lower, safer dose, or ceased. At present there is very little research available on comparative effectiveness of interventions for opioid withdrawal in CNCP.¹⁵⁰

GPs should regularly assess whether the patient satisfies the legal definition of drug dependence. If the patient has an opioid use disorder, opioid therapy for pain should be discontinued and the addiction professionally, sympathetically and appropriately treated. Seek authority from the state regulatory authorities when treating these patients.

Managing opioid tapering or discontinuation

Before attempting opioid discontinuation, GPs should be familiar with opioid reduction and withdrawal processes and patient experiences.^5,90 Some patients will experience stable or improved pain after an opioid taper.^151–153 However, short-term withdrawal can lead to transitory increased pain and hyperalgesia.^154–156 For patients with long-term opioid treatment for CNCP:

• there is no published comparison of speed of tapers¹⁵⁷
• there is no evidence to support switching to buprenorphine or methadone for tapering¹⁵⁷
• key predictors of opioid tapering dropout or relapse are depression, high pain scores and high opioid doses¹⁵⁷ (there is not yet any research to support addressing these factors through pharmacologic and psychological interventions). These patients are also those at higher risk of opioid-related adverse events and tapering of the dose should be strongly considered
• the use of α2-adrenergic agonists (eg clonidine) can reduce symptoms of withdrawal via sympathetic activity.

Where there is no evidence of substance use disorder

If weaning is required after a shorter period of opioid therapy, such as after failure to achieve the goals of an opioid trial, or after a negotiated treatment phase for acute pain, then a faster rate of weaning is generally appropriate. One option is a stepwise reduction of the daily opioid dose each week by 10–25% of the starting dose.⁵

If weaning is required in response to significant adverse effects or opioid misuse, then daily stepwise reduction may be more appropriate. Alternatively, immediate opioid cessation and pharmacological treatment of withdrawal symptoms can be considered.

Otherwise, a decrease of 10% of the original dose every 5–7 days until 30% of the original dose is reached, followed by a weekly decrease by 10% of the remaining dose, rarely precipitates withdrawal symptoms and facilitates adherence.¹⁵⁷

Where there are complex patient comorbidities

Discontinuing opioid therapy is often hindered by patients’ psychiatric comorbidities and poor coping skills, as well as the lack of formal guidelines for the prescribers.

If a previous attempt at opioid weaning has proven unsuccessful, then the rate of tapering can be slowed. This can be achieved by reducing the size of the dose reduction each month and/or by increasing the time spent at each dose level (eg two or three months between reductions).

Where there is evidence of substance use disorder

Importantly, the legislative requirements for prescribing S8 drugs vary depending on the person’s dependence, but all are consistent for patients with respect to SUD: S8 medications (most opioids, alprazolam and flunitrazepam) cannot be prescribed without a permit or an appropriate approval from the relevant state or territory health department’s pharmaceutical services unit.

In some cases, it may become apparent during weaning that the primary problem is opioid dependency rather than pain. For patients with opioid use disorder, GPs should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine-naloxone or methadone in combination with behavioural therapies). Referral to an addiction specialist is advised.^5,8

Monitoring the taper

The goal of tapering is to improve or maintain patient wellbeing while opioids are being withdrawn. Schedule frequent visits and ask about and emphasise the benefits of taper (eg improved pain, mood, alertness) at each appointment. Referral for counselling or other support during the taper is recommended, especially if there are significant behavioural issues. If a patient is not successfully reducing their dose, or there is an escalation in dose beyond prescription, involve other practitioners.

Managing withdrawal symptoms

Symptoms of withdrawal, such as nausea, diarrhoea, muscle pain and myoclonus can be managed with clonidine 0.1–0.2 mg orally every six hours, or simple supportive therapy. Symptoms of mild opioid withdrawal may persist for six months after opioids have been discontinued. However, do not treat withdrawal symptoms with opioids or benzodiazepines after discontinuing opioids.