- Chronic non-cancer pain (CNCP) is a collection of clinical conditions that may have involvement of single or multiple pathophysiological mechanisms leading to persistent pain.
- Outside of end-of-life care, the research on long-term opioid therapy for chronic pain remains limited and insufficient to determine long-term benefits. Available evidence suggests dose-dependent risk of serious harms.
- Guidelines identify only a selective place for opioids in the management of some chronic pain conditions; opioid use is not routine and is not first-line or second-line therapy. Opioids for CNCP should be reserved for selected patients with moderate or severe pain that significantly affects function or quality of life and that has not responded to other therapies.
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
Management of CNCP should be based on a comprehensive biopsychosocial assessment, a diagnosis, and thoughtful consideration of the likely risks and benefits of any intervention or medication.
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).
This will inform the selection of treatment options most likely to be effective. The assessment may need to be repeated reasonably frequently, particularly while establishing a diagnosis and appropriate pain management.
Non-drug therapies for chronic pain
The basis for good pain management is a strong continuous therapeutic relationship.
Non-drug therapy and non-opioid pharmacologic therapy are preferred for chronic pain8
Strong recommendation, low quality of evidence
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 patient5,78,86,89–93 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
Long-term opioid therapy is dependent on an appropriate patient selection process, considered care planning, and an ‘opioid trial’ to determine responsiveness to opioid treatment.
GPs should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or dangerous combinations that put him or her at high risk for overdose
Strong recommendation, very low quality of evidence
Before starting opioid therapy, GPs should evaluate risk factors for opioid-related harms8
Strong recommendation, very low quality of evidence
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
- Long-term opioid therapy is dependent on an appropriate patient selection process, considered care planning, and an ‘opioid trial’ to determine responsiveness to opioid treatment.
- A treatment plan is discussed including a plan to discontinue opioids if there is no objective functional improvement.
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 risks8,92
- 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 testing5,78,92,93,102 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.
Box 2. Naloxone
Discussion about take-home naloxone (THN) as part of an overdose response plan is an effective brief intervention. The use of naloxone fits within both harm reduction strategies and patient-centred care. Naloxone is safe, effective, inexpensive, and relatively easy to administer via intramuscular (IM) injection.106–108
Naloxone injection is dual listed as a Schedule 4 medicine subsided by the Pharmaceutical Benefits Scheme (PBS), and as a Schedule 3 medicine available from a pharmacist. It is beneficial for GPs or pharmacists to provide patients with brief instructions on how to prevent, recognise and respond to overdose including how to store, carry and administer naloxone. It may be appropriate to involve the patient’s family and/or other potential overdose witnesses relevant to the patient, as these are the people most likely to be responding to an overdose. GPs should also advise patients that naloxone can be obtained over-the-counter (OTC) from local pharmacies by a third party to protect co-residents (eg children) of the patient from intentional or unintentional overdose.
Prescribers are encouraged to provide a prescription for THN for patients at high-risk of overdose (eg high opioid dose, complex care, or recently released from a controlled environment). For further resources on naloxone therapy, refer to the Cope Australia website.
Box 3. Care planning tool
All patients prescribed longer-term opioids for CNCP should have a care plan, and one principal prescribing doctor nominated. The patient should be managed primarily by the one GP. When the principal GP is absent, another GP should be designated to manage the patient in accordance with the care plan.
A simple tool for care planning in chronic pain is available at the NSW Pain Management Network website.
Care planning for high-risk patients
For GPs with a specific interest in this area, guidance for planning and use of care plans in high-risk patients has been developed by the NSW Department of Health for both opioid dependent patients and patients with severe comorbidity.
Undertaking an opioid trial
An opioid trial is undertaken to discover the individual’s responsiveness to opioid therapy in terms of decreased pain, increased function and improved quality of life.
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 therapy requires ongoing structured monitoring and review of benefits and harms.
- GPs should taper and discontinue opioids in the absence of functional improvement, when planned care fails, or aberrant behaviours become apparent.
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.