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Chronic non-cancer pain and opioid dependence Christopher Littlejohn BSc RMN
Alex Baldacchino MPhil MRCPych
Jonathan Bannister MB FRCA 1
J R Soc Med 2004;97:62–65
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. METHOD
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 Centre for Addiction Research and Education Scotland, Department of Psychiatry, University of Dundee; 1Pain Clinic, Ninewells Hospital and Medical School, Dundee, Scotland, UK Correspondence to: Dr Alex Baldacchino, Centre for Addiction Research and Education Scotland, Department of Psychiatry, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
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E-mail:
[email protected]
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. ARE OPIOIDS EFFECTIVE IN THE TREATMENT OF CHRONIC PAIN?
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 IF OPIOIDS ARE EFFECTIVE, DO THE RISKS OF IATROGENIC ADDICTION OUTWEIGH THE BENEFITS?
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
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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,
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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
DO THOSE WITH A PRIMARY OPIOID USE DISORDER EXPERIENCE CHRONIC PAIN, AND IF SO HOW SHOULD PAIN BE TREATED?
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 opioiddependent 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
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patients’ complex problems require the integration of expertise from specialists in pain and addiction management. CONCLUSION
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 noncancer 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 opioidinduced 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 drugseeking 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. REFERENCES
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1 American Society of Addiction Medicine [www.asam.org/ppol/ paindef.htm] accessed 26 November 2003 2 Hammersley R, Reid M. Why the pervasive addiction myth is still believed. Addiction Res Theory 2002;10:7–30 3 Davies JB (1997) The Myth of Addiction, 2nd edn. Amsterdam: Harwood Academic, 1997 4 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th edn. Washington, DC: APA, 2000 5 World Health Organization. International Statistical Classification of Diseases and Related Health Problems 1989 Revision. Geneva: WHO, 1992 6 Moore A, Edwards J, Barden J, McQuay H. Bandolier’s Little Book of Pain. Oxford: Oxford University Press, 2003 7 Medina JL, Diamond S. Drug dependency in patients with chronic headache. Headache 1977;17:12–14 8 Perry S, Heidrich G. Management of pain during debridement: a survey of US burns units. Pain 1982;13:267–80 9 Porter J, Jick H. Addiction rare in patients treated with narcotics. N Engl J Med 1980;302:123
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10 Bouckoms AJ, Masand P, Murray GB, Cassem EH, Stern TA, Tesar GE. Chronic nonmalignant pain treated with long-term oral narcotic analgesics. Ann Clin Psychiatry 1992;4:185–92 11 Dellemijn PLI. Opioids in non-cancer pain: a life-time sentence? Europ J Pain 2001;5:333–9 12 Jamison RN, Anderson KO, Peeters-Asdourian C, Ferrante FM. Survey of opioid use in chronic nonmalignant pain patients. Regional Anesthesia 1994;19:225–30 13 Arkinstall W, Sandler A, Goughnour B, Babul N, Harsanyi Z, Darke AC. Efficacy of controlled-release codeine in chronic non-malignant pain: a randomized, placebo-controlled clinical trial. Pain 1995;62:169–78 14 Moulin DE, Iezzi A. Randomised trial of oral morphine for chronic non-cancer pain. Lancet 1996;347:143–7 15 Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999;53:1959–64 16 Portenoy RK. Opioid therapy for chronic nonmalignant pain: a review of the critical issues. J Pain Symptom Management 1996;ii:203–17 17 Chong MS, Bajwa ZH. Diagnosis and treatment of neuropathic pain. J Pain Symptom Management 2003;25(suppl.):S4–11 18 Bannwarth B. Risk–benefit assessment of opioids in chronic noncancer pain. Drug Safety 1999;21:283–96 19 Collett BJ. Chronic opioid therapy for non-cancer pain. Br J Anaesth 2001;87:133–43 20 Nicholson B. Responsible prescribing of opioids for the management of chronic pain. Drugs 2003;63:17–32 21 Strumpf M, Dertwinkel R, Wiebalck Bading B, Zenz M. Role of opioid analgesics in the treatment of chronic non-cancer pain. CNS Drugs 2000;14:147–55 22 Heit HA. The truth about pain management: the difference between a pain patient and an addicted patient. Europ J Pain 2001;5(suppl. A): 27–9 23 Adriaensen H, Vissers K, Noorduin H, Meert T. Opioid tolerance and dependence: an inevitable consequence of chronic treatment? Acta Anaesthesiol Belg 2003;54:37–47 24 Aronoff GM. Opioids in chronic pain management: is there a significant risk of addiction? Curr Rev Pain 2000;4:112–21 25 Passik SD, Weinreb HJ. Managing chronic nonmalignant pain: overcoming obstacles to the use of opioids. Adv Ther 2000;17:70–83 26 Fishbain DA, Rosomoff HL, Rosomoff RS. Drug abuse, dependence, and addiction in chronic pain patients. Clin Pain 1992;8:77–8 27 Savage S. Opioid therapy of chronic pain: assessment of consequences. Acta Anaesth Scand 1999;43:909–17 28 Zenz M, Strumpf M, Tryba M. Long-term oral opioid therapy in patients with chronic nonmalignant pain. J Pain Symptom Management 1992;7:69–76 29 Hoffman NG, Olofsson O, Salen B, Wickstrom L. Prevalence of abuse and dependency in chronic pain patients. Int J Addictions 1995;30:919–27 30 Savage SR. Assessment for addiction in pain-treatment settings. Clin J Pain 2002;18(suppl.):S28–38 31 Kouyanou K, Pither CE, Wessely S. Medication misuse, abuse and dependence in chronic pain patients. J Psychosom Res 1997;43:497–504 32 Maruta T, Swanson DW, Finlayson RE. Drug abuse and dependency in patients with chronic pain. Mayo Clinic Proc 1979;54:241–4 33 Reid MC, Engles-Horton LL, Weber M, Kerns RD, Rogers EL, O’Connor PG. Use of opioid medications for chronic noncancer pain syndromes in primary care. J Gen Intern Med 2002;17:173–9 34 Jonasson U, Jonasson B, Wickstro¨m L, Andersson E, Saldeen T. Analgesic use disorders among orthopedic and chronic pain patients at a rehabilitation. Substance Use Misuse 1998;33:1375–85 35 Dunbar SA, Katz NP. Chronic opioid therapy for nonmalignant pain in patients with a history of substance abuse: report of 20 cases. J Pain Symptom Management 1996;11:163–71
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36 Weissman DE, Haddox JD. Opioid pseudo-addiction: an iatrogenic syndrome. Pain 1989;36:363–6 37 Compton P, Darakjian J, Miotto K. Screening for addiction in patients with chronic pain and ‘‘problematic’’ substance use: evaluation of a pilot assessment tool. J Pain Symptom Management 1998;16:355–63 38 Bendtsen P, Hensing G, Ebeling C, Schedin A. What are the dilemmas experienced when prescribing opioids in general practice? Pain 1999;82:89–96 39 Longo LP, Parran T, Johnson B, Kinsey W. Addiction: Part II. Identification and management of the drug-seeking patient. Am Family Physician 2000;61:2401–8 40 Stein MD, Mulvey KP, Plough A, Samet JH. The functioning and well being of persons who seek treatment for drug and alcohol use. J Substance Abuse 1999;10:75–84
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41 Kennedy JA, Crowley TJ. Chronic pain and substance abuse: a pilot study of opioid-maintenance. J Substance Abuse Treatment 1990;7: 233–8 42 Rosenblum A, Joseph H, Fong C, Kipnis S, Cleland C, Portenoy RK. Prevalence and characteristics of chronic pain among chemically dependent patients in methadone maintenance and residential treatment facilities. JAMA 2003;289:2370–8 43 Jamison RN, Kauffman J, Katz NP. Characteristics of methadone maintenance patients with chronic pain. J Pain Symptom Management 2000;19:53–62 44 Compton P, Charuvastra VC, Ling W. Pain intolerance in opioidmaintained former opiate addicts: effect of long-acting maintenance agent. Drug Alcohol Dependence 2001;63:139–46 45 Weaver M, Schnoll S. Abuse liability in opioid therapy for pain treatment in patients with an addiction history. Clin J Pain 2002;18(suppl.):S61–9
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