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There are four main questions to address on the subject of chronic non-cancer pain and opioid addiction. Are opioids effective in the treatment of such pain? If so, do the risks of iatrogenic addiction outweigh the benefits? To what extent do patients with primary opioid addiction experience chronic pain? How should this pain be treated?
We review the subject from a UK perspective. Most of the published work comes from the USA, where addiction tends to be viewed primarily as a neurobiological disease or disorder, albeit one that can be influenced by environmental factors.1 UK workers are less inclined to privilege the biological over the psychosocial—readier to accept that people can make heavy use of drugs without being addicted, that the heavy use of drugs can be a choice rather than 'loss of control', and that many people can modify their drug consumption without help.2 Indeed, there are those who see addicts' descriptions of their 'compulsive behaviours' as an artifact of the social and legal prohibitions on the use of drugs (i.e. that the claim 'I only take drugs because I am addicted' is merely a post-hoc rationalization).3 Even in the treatment of pain, the prescription of opioid analgesics has waxed and waned according to the fashion of the moment.
The term addiction is ubiquitous in the published work but is no longer found in either of the contemporary diagnostic manuals, the Diagnostic and Statistical Manual of Mental Disorders (DSM)4 or the International Classification of Diseases (ICD).5 We use it here because it retains ideas about 'loss of control' and chaotic drug use despite adverse physical, mental and social consequences.
To address the four questions we searched CINAHL, Embase, MEDLINE and PsycINFO with the terms 'chronic pain', 'addiction', 'drug abuse', 'opioid dependence', and 'substance dependence'. The search was confined to papers published in the past ten years: we decided that older papers that had 'stood the test of time' would continue to be cited. A total of 555 records were retrieved, of which 266 were selected by scrutiny of abstracts. We excluded papers that were not in English, that did not deal with human addiction, that addressed chronic cancer-related pain, and that were unrelated to opioid use disorders. We found 102 relevant papers, including those identified from a citation search. These comprised 34 primary papers (i.e. empirical research reports) and 68 secondary papers (reviews and opinions). Most of them originated from the USA (67, compared with the UK contribution, in second place, of 12). The largest body of work—24 primary papers, all the secondary papers—addressed the treatment of chronic pain with opioids. The remaining 10 dealt with chronic pain in patients being treated for a primary opioid addiction.
Although opioid analgesics are now widely used for pain and in palliative care,6 this was not always so. Even in acute pain, several studies were required to dispel the myth that a single dose could create addiction.7-9 That opioids can be effective in chronic pain is not in doubt:10-12 for example, placebo controlled studies have demonstrated the value of codeine,13 and of morphine in chronic pain unrelieved by other treatment.14 Even neuropathic pain, which is often opioid-resistant,15 is not consistently unresponsive;16 comment on this matter is made difficult by a shortage of rigorous research.17
Discussion of the addictive potential of opioids features mainly in reviews and expert guidance for clinicians on the careful use of opioids in chronic pain.18-21 Some argue that patients at high risk of iatrogenic addiction can be identified and excluded;16,22 others declare that the risks of iatrogenic addiction have been exaggerated to the extent that no patient with chronic pain should be deprived of effective treatment.23-25 Expert opinion currently leans to the view that, in chronic pain, opioid treatment does not carry a high risk of iatrogenic addiction.26-28
Can the risk be quantified? This is a concern for patients as well as clinicians. In a 1994 survey of chronic pain patients taking long-term opioids, nearly two-thirds expressed anxiety that they might become addicted, though the same proportion had not had to increase their consumption of the drugs. Prevalence studies have done little to clarify matters. Some have been essentially negative. For example, Moulin and Iezzi14 found no instances of addiction in their 22-week study of oral morphine; and Dellemijn11 saw no withdrawal effects or addictive behaviour in 5 patients treated for up to two years with transdermal fentanyl.
The study by Hoffman and colleagues,29 using DSM-III-R criteria in chronic-pain patients, gave more cause for concern, finding 'analgesic misuse' in 1.9% and 'analgesic dependence' in 12.6%. This was to be compared with a prevalence rate of addiction in the general population of between 3% and 26%.30 Kouyanou and colleagues,31 in the UK, likewise used DSM-III-R criteria in chronic-pain patients and found opioid abuse in 3.2%, opioid dependence in 4.8%. Other groups have reported much higher rates of substance abuse in such patients: Maruta et al.,32 in the pre-DSM-III era, 24% drug dependence, 41% drug abuse; Reid et al.33 prescription opioid abuse by 24-31%; Bouckoms et al.10 24% 'serious narcotic abuse', 27% 'narcotic addiction'. However, any attempt to measure prevalence is wholly dependent on the definitions. For example, in one study the prevalence of 'analgesic substance use disorder' was 22% with DSM-III criteria, 18% with DSM-IV criteria.34
There is reason to question the validity of criteria for substance abuse disorders. In their retrospective study of opioid therapy for chronic pain, Dunbar and Katz identified 20 patients with a previous history of substance misuse.35 They divided these patients into two groups according to whether the treating physician suspected them of being addicted to their prescribed opioids. Those who were judged to show addictive behaviour, such as unauthorized dose escalations or 'doctor shopping', were noted to have significantly more unrelieved pain than the non-addicted group. This raised the possibility that what appears to be addiction in some chronic pain patients is the same as the 'pseudo-addiction' reported in patients with cancer whose pain is unrelieved, and whose addictive behaviours disappear once pain relief is achieved.36 When we consider the diagnostic criteria for substance dependence as they appear in both DSM-IV and ICD-10, their inadequacies in this group become obvious. First, in long-term opioid treatment, one or both of the physiological criteria (tolerance and withdrawal) are likely to develop, but in the context of pain management are not to be regarded as pathological (it is noteworthy that many illicit addicts do not demonstrate these physiological changes30). Second, the behavioural criteria (e.g. increasing importance of acquiring and using the drug, compulsion to use, impaired control, reduced social or recreational activities) can be a manifestation, in the chronic-pain patient, of therapeutic dependence—attempts to secure supplies of analgesia in the face of fear and anxiety about running out of analgesics, or of worsening or breakthrough pain.37 Chronic pain by its nature reduces peoples' desire and ability to socialize or remain active, and is a major risk factor for depression. Furthermore, for those whose pain is unrelieved, the desperate visits to multiple practitioners (seeking one who will take their pain seriously), the quest for analgesic drugs, can give a false impression of addiction.
These shortcomings have been recognized by some groups, and there have been attempts in the US to create diagnostic criteria for identifying pathological addiction in the context of opioid treatment for chronic pain. However, provisional testing of the new criteria has still found that one in five 'non-addicted' patients will demonstrate the very behaviours taken to be diagnostic of addiction.37
Practitioners tend to be cautious when patients report pain, knowing that some exaggerate or lie so as to obtain opioids for the drugs' psychoactive properties.38 Meanwhile, practitioners who 'over-prescribe' have been condemned as 'dated, duped, dishonest or disabled'—out-of-date with contemporary practice; duped by manipulative patients; dishonest in providing illicit prescriptions for material gain; or disabled, in being themselves affected by a chemical dependency or personality disorder that distorts their prescribing practices.39 Yet patients with primary opioid dependence do report high levels of chronic pain, even when intuition would suggest that they should experience less (for example, those receiving methadone maintenance in high daily doses).40 Although methadone has been found effective in management of comorbid opioid dependence and chronic pain,41 between 24% and 61% of individuals on methadone maintenance report chronic pain.42,43 There is much experimental evidence that those receiving methadone maintenance have lower pain thresholds than controls (i.e. that they feel pain more easily).44
There is good reason therefore to consider the opioid-dependent population as being likely to experience chronic pain. It seems doubtful that the simple exposure to opioid medicines, when they are used to treat chronic pain, risks making a current addiction worse or rekindling an addiction that has been previously overcome. Even those with a history of substance use disorders can have their chronic pain effectively treated with opioids.45 The primary task would seem to be to increase our ability to identify patients who falsely seek opioid drugs in the absence of pain. These patients' complex problems require the integration of expertise from specialists in pain and addiction management.
The published work on comorbid chronic pain and addiction is dominated by opinion rather than evidence. We suspect that, as happened previously with acute pain and palliative care, fears about addiction from opioid therapy in chronic non-cancer pain have been excessive. This is not to argue that opioids are always the drug of choice for chronic pain—just that excluding them a priori appears based more upon ignorance than on science. Of course, opioids are not 'ordinary' medicines, subject as they are to serious cultural and legal sanctions for unprescribed use. Yet perhaps the opioids' special legal status adds to the need to separate their 'proper' medicinal (analgesic) properties from their prohibited psychoactive properties. (Are we sure that opioid-induced euphoria is a 'bad thing' in those whose lives are blighted by unremitting pain?) What is problematic is the insensitivity of our current tools for telling us when patients are running into difficulties with their prescribed opioids. They do not allow us to differentiate between the drug-seeking opioid 'addict' and the patient who is desperate because of unrelieved pain. We cannot objectively tell the addicted from the pseudo-addicted. Probably the tools for such differentiation should be developed locally rather than imported from the USA, where the concepts differ.
The finding of high pain levels in the context of maintenance opioid treatment of addiction merits further research. Does long-term administration of opioids modify pain perception, or do those who develop primary opioid addiction inherently differ in their perception or experience of pain? It would be wise to temper scepticism when such individuals complain of pain.