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Abstract

Evidence base: A Medline search of the literature since 1966 produced 163 relevant articles, including two randomised controlled trials of oral opioids in non-cancer pain.

Management consensus

• A small group of patients with chronic non-cancer pain can benefit from the use of oral opioids.
  
• Thorough attention to diagnosis and patient history must precede any decision to prescribe opioids.
  
• Patients should be psychologically stable.
  
• Patient and doctor should agree beforehand on how to assess the outcome of therapy.
  
• Only one doctor (the patient's regular primary carer or pain specialist) should prescribe opioids and assess the response.
  
• Sustained release morphine preparations are the drug of choice.
  
• A trial of therapy, with goals and endpoint agreed between patient and doctor, should precede any decision to prescribe opioids in the long term.

MJA 1997; 167: 30-34  

Introduction

Data from recent randomised controlled trials^3-5 support the finding of benefit in retrospective studies of patients treated with opioids for chronic non-cancer pain.^6,7 This evidence suggests that a proportion of patients report an improvement in their level of analgesia and/or level of function.⁸ The prevalence of drug abuse, dependence and addiction has been estimated to be as low as 3.2%⁹ or as high as 18.9%,¹⁰ depending on definition. Fishbain et al. report that there is little evidence that addictive behaviours are common in the chronic pain population.¹¹

There is evidence, however, that an increasing number of Australian patients are receiving prescribed oral opioids for both malignant and non-malignant pain.¹² This may be filling a previously unmet need, but it is not clear if the increased prescribing for non-cancer pain is appropriate, whether there has been any increase in function, reduction of pain, reduction in suffering, or if any of these drugs will enter the illicit market.

How then can we ensure the maximum benefit from the prescription of opioids for chronic non-cancer pain? Who are the appropriate patients? Who are the appropriate prescribing doctors? How should the drugs be prescribed? Which drugs should be prescribed? How and when should they be withdrawn? The aim of this article is to explore these issues and provide guidelines to assist practitioners in the appropriate use of oral opioids.  

Which patients?

A thorough history of previous conservative therapy ( Box 1) should be taken before consideration is given to the medium to long term use of opioids. Previous drug therapy should include trials of non-opioid analgesics, tricyclic antidepressants and membrane-stabilising medications (e.g., sodium valproate, carbamazepine, mexiletine).

Patients for whom opioids are being considered should be psychologically stable, although it is recognised that this is difficult to define. Patients in chronic pain may develop psychological problems as a result of the pain, and therein lies a dilemma for the physician. Will treating the pain reverse some of the psychological abnormalities? Or are the psychological abnormalities a significant contributor to the overall pain behaviour? Studies would suggest the former in most cases.¹³

A psychological assessment is essential for patients with poorly defined pathology, younger age, high levels of distress, or previous or ongoing substance abuse. Consideration should be given to managing these patients in a multidisciplinary pain centre ( Box 2).  

Which doctors should prescribe?

It is important that only one doctor prescribes the opioids and assesses the response. Patient and doctor must agree on how to assess the outcome of therapy before opioids are prescribed. Failure to reach the predetermined goals is an indication to cease prescribing.

All patients who are considered suitable for the long term use of opioids in non-cancer pain should be assessed at some stage in a specialist pain management centre. Shared care between the general practitioner and the pain management centre is ideal.  

Which drug?

There is agreement internationally¹⁴ and within Australia¹⁵ that intramuscular opioids should not be used to treat chronic non-cancer pain. In particular, intramuscular pethidine should be avoided. It has a short half-life, possibly an increased risk of dependence due to its psychomimetic effects, and the potential for excitatory central nervous system effects from accumulated norpethidine concentrations after repeated doses.

Codeine phosphate is a short-acting drug and as such has little place in chronic pain management. A controlled release preparation is available overseas and may prove useful.

Immediate release morphine as morphine mixture (5-10 mg/mL) may be used for dose finding before beginning the use of sustained release morphine, but is generally unnecessary. It may be useful for breakthrough pain or exacerbations.

Transdermal fentanyl patches may, in the future, provide a useful alternative for patients intolerant of morphine.

Methadone and oxycodone rectal suppositories are useful alternatives to oral sustained release morphine preparations.

Dietary advice should be given to minimise the problem of constipation and consideration should be given to the regular use of laxatives.  

Consent

Informed consent should include discussion of:

• Clearly defined specific goals of the treatment program.
• The likelihood of dependence and the risk of addictive behaviour. All patients will become dependent and are likely to experience withdrawal symptoms if opioid therapy is suddenly stopped. Addictive behaviour occurs in a much smaller proportion of patients and may be minimised by appropriate patient selection.
• The lack of published data on long term outcome of the effects of medically prescribed opioids.
• The potential for cognitive impairment, in particular that might affect driving ability. While there are few studies in non-cancer patients assessing cognitive function in the presence of opioids,¹⁷ the studies in cancer patients would suggest that cognitive function is actually improved when adequate analgesia is provided.¹⁸
• The potentiating effect of opioids on the sedative effect of other medication.
• The possibility (for women) of physical dependence in children born to them if they continue to take opioids in late pregnancy.
• Indications for the cessation of treatment with opioids.
• The patient's responsibilities regarding the security of his or her medication. The consequences of aberrant behaviour ( Box 3) should be identified as clearly as possible.
• Side effects (e.g., constipation, nausea, sedation, dry mouth).

How should these drugs be prescribed?

Trial of oral opioid

There is controversy regarding the expectation that patients will improve in function. Is it adequate for patients to achieve analgesia only? Is it adequate for patients to state that they feel better only? Certainly patients should reduce their use of other analgesics; ideally, they should show improved function. Perception of improved analgesia should be the minimal requirement, and failure to achieve at least partial analgesia at a moderate dose contraindicates any further long term opioid treatment.

Most patients who experience minimal or no analgesic effect will stop taking the drug themselves before the end of the trial. Similarly, many patients who experience adverse side effects, such as severe nausea or constipation, will determine that these outweigh the analgesic benefits and stop taking the drug. Opioid-naive patients whose dose rapidly escalates within a month of starting treatment should generally be considered inappropriate for long term opioid therapy.

At the end of the trial period, if the expected outcomes have not been achieved, the drug dose should be tapered over a few days and ceased.  

Ongoing reviews

Evidence of aberrant behaviour should be assessed. Aberrant behaviour is variable in its importance and relevance. Box 3 indicates factors which Portenoy²⁰ has considered more or less predictive of the development of addictive behaviour. Patients identified with behaviour in the less predictive category indicate a need to assess the dose of drug, the psychological factors of relevance, the patient's expectations or the type of medication.

If patients are identified with features in the more predictive category, the appropriateness of opioid prescription should be seriously reassessed. Often it will be necessary to reduce and then withdraw the opioid over a week. In other cases, a more regulated supply, such as daily or weekly prescriptions, may be appropriate. An initial written consent form indicating those factors for which supply will be withdrawn will make this easier.  

References

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