WS #107 & #118 Widespread Pains and Nothing to be Found: Pain Clinic Approaches. John Alchin Pain Management Centre Burwood Hospital 15.8.

Transcription

1 WS #107 & #118 Widespread Pains and Nothing to be Found: Pain Clinic Approaches John Alchin Pain Management Centre Burwood Hospital

2 Burwood Pain Management Centre ,200 new patient referrals received 380 new patients were seen ie, < 20% of referrals able to be seen

3 GBD 2010 Study Hoy DG, et al. Ann Rheum Dis 2015;74:4 7. Vos T et al. Lancet 2012; 380: The main contributors to global YLDs: 1. mental & behavioural disorders, 2. musculoskeletal disorders, & 3. diabetes or endocrine diseases.

4 GBD 2010 Study Hoy DG, et al. Ann Rheum Dis 2015;74:4 7. Vos T et al. Lancet 2012; 380: The leading specific causes of YLDs were much the same in 2010 as they were in 1990: 1. low back pain, 2. major depressive disorder, 3. iron-deficiency anaemia, 4. neck pain, 5. chronic obstructive pulmonary disease, 6. anxiety disorders, 7. migraine, 8. diabetes, 9. falls.

5 GBD 2010 Study Hoy DG, et al. Ann Rheum Dis 2015;74:4 7. Vos T et al. Lancet 2012; 380: Prevalence & burden from MSK conditions exceptionally high throughout the world. 291 conditions studied: LBP ranked highest in terms of years lived with disability (YLD), & 6 th in overall burden (disability-adjusted life years DALYs) Neck Pain: 4 th highest for YLD, & 21 st for DALYs Other MSK disorders: 6 th highest for YLD, & 23 rd for DALYs. As a group, MSK conditions 21.3% of total YLD in the world, 2 nd to mental & behavioural problems (23.2%). Taking into account death & disability, MSK conditions are 4 th greatest burden on health of the world s population (3 rd in developed countries), 6.7% of the total global DALY.

6 PHYSIOLOGY KEY POINTS 1. Pain as an output of the brain 2. Nociceptive ( pain ) system as a sub-division of the (peripheral & central) nervous system 3. The concept of disorders of the nociceptive system; in particular: 4. The importance of central neural sensitisation, ie, sensitisation of nociceptive pathways in the CNS

7 MANAGEMENT KEY POINTS Empirical Medical First-Line medications: Nor-adrenergic ADs TCAs, SNRIs Gabapentinoids gabapentin, pregabalin Limited Role of Opioids Analgesic Report Card: C Interdisciplinary pain self-management CBT, exercise

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19 Pain Perception is Normally Distributed Diatchenko et al: Human Molecular Genetics, 2005, Vol. 14, No. 1; pp

20 MEDICAL MYSTERIES 1 BUILDERS, NAILS, & PAIN

21 A builder aged 29 came to the accident and emergency department having jumped down on to a 15 cm nail. As the smallest movement of the nail was painful he was sedated with fentanyl and midazolam. The nail was then pulled out from below. When his boot was removed a miraculous cure appeared to have taken place. Despite entering proximal to the steel toecap the nail had penetrated between the toes: the foot was entirely uninjured.--j P FISHER, senior house officer, D T HASSAN, senior registrar, N O'CONNOR, registrar, accident and emergency department, Leicester Royal Infirmary. Fisher, J P et al. BMJ 1995;310:70 Copyright 1995 BMJ Publishing Group Ltd.

22 Neurotransmitters Somatic Deamplification. Reprinted from Associated Press, World Wide Photos 1/ USA Today described a construction worker who had unknowingly shot himself in the head with a nail gun, & was unaware of the injury. Due to a toothache he attended a dentist 6 days later, where the cause of the toothache was discovered. Dimsdale JE, Dantzer R: 2007

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26 MEDICAL MYSTERIES EXPLAINED PAIN (& VISION) AS OUTPUTS OF THE BRAIN

27 Definition of pain IASP, 1979 Pain is an unpleasant sensory & emotional experience associated with actual or potential tissue damage, or described in terms of such damage

28 (Woolf, 2010)

29 4 main kinds of pain: SUMMARY Adaptive Pain (normal, physiological): - Nociceptive - Inflammatory Maladaptive Pain (abnormal, pathological): - Neuropathic - Dysfunctional

30 Cortical and sub-cortical regions involved in pain perception, their inter-connectivity and ascending pathways. Locations of brain regions involved in pain perception are color-coded in a schematic drawing and in an example MRI. (a) Schematic shows the regions, their inter-connectivity and afferent pathways.

31 n engl j med 359;5. July 31, 2008 A n otherwise healthy and functional 35-year-old man had an undisplaced fracture of the right fifth metacarpal neck after a fall. He presented 21 months later with pain, extensive swelling (Panels A and B), and loss of function in his right hand up to the middle third of his upper arm. On physical examination, there was nonpitting edema, hair loss, allodynia, and vasomotor instability, with increased temperature, sweating, and erythema. These changes had developed since the initial fracture and had progressed slowly. Radiologic studies showed that the fracture had healed (Panel C). Computed tomography of the chest showed axillary lymphadenopathy that was consistent with a benign reactive process. The patient received a diagnosis of complex regional pain syndrome type 1

32 (Yunus, 2007, 341) Also non-cardiac chest pain; chronic abdominal pain

33 Include: Pain Assessment History FH, eg of chronic pain, migraine PH: other pain problems (eg, IBS, FMS, IC, CFS): file review often necessary Psychological co-morbidities: common, but not inevitable: Affective (Anxiety / Depression) Cluster B Personality Disorder / Traits Substance Abuse / Dependence

34 Drug Treatment of Chronic Pain Principles Moore A, Derry S, Eccleston C, Kalso E: Expect Analgesic Failure; Pursue Analgesic Success. British Medical Journal; BMJ 2013;346:f2690 (Published online 3 May 2013; print edition ) Doi: See also R. Andrew Moore: Review. What works for whom? Determining the efficacy and harm of treatments for pain ; Pain 154 (2013) S77 S86

35 Drug Treatment of Chronic Pain Principles starts by recalling a 2003 newspaper article by the chief of Glaxo entitled, Our drugs do not work on most patients, stating that most drugs work in only 30-50% of people. While that surprised journalists and the public, it was not news to professionals.

36 Evidence for analgesic efficacy Evidence for analgesic efficacy (those with a success rate > 50%) in 4 types of pain ( success = 50% or more pain reduction in 50% or more of those randomised to active drug) Acute postoperative pain only 4 of 10 analgesics. Acute migraine only 1 of 6 medications Chronic musculoskeletal pain (osteoarthritis, chronic low back pain, fibromyalgia, ankylosing spondylitis) none of 19 medications Neuropathic pain (painful diabetic neuropathy, postherpetic neuralgia) none of 9 medications Message: Very sobering. No Triumphalism. Be realistic. Expect Analgesic Failure.

37 Analgesia not normally distributed Pain relief is not normally distributed, but usually bimodal, being either very good (> 50%) or poor (< 15%). That is, any given analgesic tends to either: Work quite well (but only in a small minority of patients 10-15%); or Not work at all (in 85-90% of patients).

38 Responders vs Non-Responders Responders: (a minority) success is often achieved within the first 2 weeks or so of treatment or not at all, & tends to last. Those who get better (responders) do well: recent individual patient analyses for chronic pain interventions have shown that people who respond experience improvements in fatigue, depression, and sleep & general measures of function and quality of life, including ability to work. Non-responders (the majority) have none of these benefits.

39 Explanation & Implications These disappointing results not unexpected: Chronic pain conditions are complex, and associated with considerable comorbidity. Coupled with the intricacies of pain modulation, central nervous system changes, and genetic influences, high failure rates with single interventions are unsurprising. The magnitude of the failure to achieve good pain relief, especially over the longer term in chronic pain, is sobering Requiring a radical rethink of achievable analgesic effects.

40 Average benefits have no part in these discussions. Using averages is unhelpful and misleading, because average pain relief is actually experienced by few (if any) patients, and it tells us nothing about how many patients will experience clinically useful pain relief.

41 3 guiding principles for the best clinical use of analgesics: 1. measure pain in individual patients, 2. expect analgesic drugs to fail to provide a good response in most patients, 3. prepare for the next step when failure occurs react to it, pursuing analgesic success, rather than blindly accepting failure.

42 Minimises Side-Effects An important advantage of this responder analysis approach to assessing analgesic efficacy is that it minimises patient exposure to adverse drug effects: In the (likely) event of analgesic trial failure, patients without benefit should be exposed to no risk, because the drug is stopped; only effective drugs should continue to be prescribed. On the other hand, With success, considerable benefits in terms of pain relief, sleep, fatigue, depression, function, and quality of life, are balanced against rare risk of serious harm.

43 Policy implications of analgesic efficacy data, & approach to clinical analgesics use 1. Guideline developers often restrict treatment options to one or two drugs (such as, the NICE neuropathic pain guideline). They consider similar drugs to operate as a class, and so select one as the first or only option, despite possibly important differences in pharmacokinetics or drug interactions. Less restrictive guidance, centred on patient-clinician interaction, and a large dose of clinical wisdom as well as evidence, may do better.

44 2. Regulatory authorities also need to recognise that failure is the norm. European regulators, unlike their US counterparts, have refused to license any drug in fibromyalgia because of inadequate average effect size, ignoring the fact that these drugs work well ( 50% reduction in pain intensity) in around 10% of patients with this difficult to treat condition. New drugs are unlikely to be much better. A change in regulatory attitude is overdue Because success rates are low, a wide range of drugs is needed to do the best for most patients, especially in complex chronic conditions.

45 Drug Treatment of Chronic Pain Principles 1. It is OK to use analgesics for chronic pain, just as it is to use medications to lower high blood pressure. 2. It is up to you to decide if you will use analgesics (self-management). If you do: 3. A trial: weigh good effects (eg, on pain relief, & improved sleep) vs side effects 4. Available analgesics are not very good

46 4. Available analgesics are not very good 76 trials reporting on 34 treatments were included. 50% of the investigated treatments had statistically significant effects, but for most the effects were small or moderate... the analgesic effects of many treatments for non-specific low back pain are small Machado LAC et al: Analgesic effects of treatments for non-specific low back pain: a meta-analysis of placebo-controlled randomized trials ; Rheumatology 2009; 48:

47 4. Available analgesics are not very good 59 drugs identified as analgesics were introduced from 1960 to 2009 and remain in use... only one, sumatriptan, was sufficiently effective to motivate the introduction of many similar drugs acting at the same target (triptans)... Very intensive research efforts directed at diverse molecular targets related to pain mechanisms produced thousands of publications, but those efforts have not yet yielded new analgesics with sufficient effectiveness... The present assessment reveals the lack of real breakthroughs in analgesic drug development despite intense research efforts. Kissin, I: SPECIAL ARTICLE: The Development of New Analgesics Over the Past 50 Years: A Lack of Real Breakthrough Drugs ; Anesth Analg; 2010;110:780 9

48 4. Available analgesics are not very good Most existing analgesics for persistent pain are relatively ineffective the number of patients who are needed to be treated (NNT) to achieve 50% reduction in neuropathic pain in one patient is more than four, a high cost for the 3 unsuccessfully treated patients and their physicians. Woolf, C: Review: Overcoming obstacles to developing new analgesics ; Nature Medicine (Supplement); 16,11: ; November 2010

49 present treatment options result in modest improvements at best, & part of chronic pain management should include dialogue with the patient about realistic expectations of pain relief, & bring focus to improvement of function Of all treatment modalities reviewed, the best evidence for pain reduction averages roughly 30% in about half of treated patients... not always occur with concurrent improvement in function none of the most commonly prescribed treatment regimens are, by themselves, sufficient to eliminate pain & to have a major effect on physical & emotional function in most patients with chronic pain. hardly surprising in view of the complexity of chronic pain. If there is no... improvement in patient pain, physical & emotional functioning, then an alternate treatment approach should be recommended. Turk DC, Wilson HD, Cahana A: Treatment of Chronic Non- Cancer Pain, The Lancet 2011; 377: ( )

50 Not only analgesia development has made little progress 1: Alzheimer s Disease Alzheimer disease (AD), first described more than a century ago, continues to challenge our generation. If we compare the therapeutic progress that modern science has made in this condition with that achieved in treating bacterial infectious diseases, we are unfortunately still in the pre-antibiotic era with respect to AD. Despite a huge leap in our understanding of the basic science and pathogenesis of this devastating neurodegenerative disease and the many clinical trials of various drugs with disease modifying potential, we have seen little real progress in achieving a cure. (JAMA Intern Med. May 27, 2013, page 901)

51 Not only analgesia development has made little progress 2: Cancer Chemotherapeutics Growing economic burden of cancer: cost of cancer drugs rising most rapidly: new cancer therapies cost > $US 10,000 a month. 71 new therapies approved by US FDA for solid tumour Rx median gain in overall survival = only 2.1 months. Fojo et al: Unintended Consequences of Expensive Cancer Therapeutics The Pursuit of Marginal Indications & a Me-Too Mentality That Stifles Innovation & Creativity ; JAMA Otolaryngol Head Neck Surg. Published 28/7/14 doi: /jamaoto

52 Drug Treatment of Chronic Pain Principles 1. It is legitimate to use analgesics for chronic pain, eg BP. 2. It is up to you to decide if you will use analgesics (selfmanagement). If you do: 3. A trial: weigh good effects (eg, on pain relief, & improved sleep) vs side effects 4. Available analgesics are not very good 5. Combinations of different medications: eg Nortriptyline + gabapentin (The Lancet; , p ) Imipramine 75 + pregabalin 300 (Pain, May 2015, ) Venlafaxine + gabapentin (J Clin Neuromuscul Dis; 2001; 3: 53 62) Morphine + gabapentin (N Engl J Med; 2005; 352: ) Morphine + nortriptyline (Pain in-press, 2015) (Gilron et al: Lancet Neurology, Nov 2013, Mao et al: J Pain, Feb 2011, )

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55 1 st -Line Drugs for Fibromyalgia Level 1 Evidence: Amitriptyline Tricyclic Duloxetine Milnacipran ) ) SNRIs Pregabalin ) Gabapentinoids Gabapentin ) Summer C: Fibromyalgia: A Clinical Update ; IASP, June 2010

56 Non-Medical Pain Management Cognitive Behavioural Therapy (CBT) Glombiewski JA et al: Psychological treatments for fibromyalgia: a Meta-Analysis ; Pain 2010: 151, Meta-analysis significant but small effect size for short-term pain reduction, small-to-medium effect size for long-term pain reduction over an average follow-up phase of 7.4 months. Psychological treatments also effective in reducing sleep problems, depression, functional status, and catastrophizing. These effects remained stable at follow-up. Moderator analyses: cognitive-behavioural treatment significantly better than other psychological treatments in short-term pain reduction. Higher treatment dose better outcome. Publication-bias analyses robust effect sizes. Results: effects of psychological treatments for fibromyalgia are: relatively small, but robust; and comparable to those reported for other pain and drug treatments.

57 Non-Medical Pain Management Cognitive Behavioural Therapy (CBT) Eccleston C et al: Psychological approaches to chronic pain management: evidence & challenges ; British Journal of Anaesthesia 2013; 111 (1): evidence for effectiveness is strongest for cognitive behavioural therapy, with a focus on cognitive coping strategies & rehearsal. clear that treatment benefit can be achieved with cognitive behavioural methods effect change in pain, mood, & disability, changes not achieved by chance, or by exposure to any other treatment. However, the overall effect sizes of treatments are modest.

58 Non-Medical Pain Management Cognitive Behavioural Therapy (CBT) Kerns RD et al: Psychological Treatment of Chronic Pain ; Annu. Rev. Clin. Psychol. 2011; 7: Psychological treatment has emerged as a common component of a multidimensional & interdisciplinary plan of pain care for many persons with persistent pain. Treatments based on biopsychosocial model of pain, & a long history of psychological research that has identified the central role of behavioural, cognitive, & emotional factors believed to contribute to the perpetuation, if not the development, of chronic pain & pain-related disability & emotional distress. Empirically supported self-regulatory, behavioural, cognitive-behavioural, & acceptance & commitment Rx.

59 Non-Medical Pain Management Kamper SJ et al: Multidisciplinary biopsychosocial rehabilitation for chronic low back pain: Cochrane systematic review & meta-analysis ; BMJ 2015;350:h444 doi: /bmj.h444 Conclusions: Multidisciplinary biopsychosocial rehabilitation interventions more effective than usual care (moderate quality evidence); & physical treatments (low quality evidence) in decreasing pain & disability in chronic low back pain. For work outcomes, multidisciplinary rehabilitation seems to be more effective than physical treatment, but not more effective than usual care.

60 Take Home Messages Chronic pain can be, & often is, a disorder of the nociceptive ( pain ) system. Especially with common psychological and pain co-morbidities. Therefore: Don t keep looking for a peripheral (nociceptive &/or inflammatory) cause. Trust your clinical judgement. Be confident. Medications are ineffective more often than not 1 st -line: TCAs, SNRIs, Gabapentinoids Minimise Ppioids CBT non-drug pain management

61 NP - MEDICATION MANAGEMENT Lancet Neurology, Feb 2015; Finnerup NB et al: Pharmacotherapy for neuropathic pain in adults: a systematic review & meta-analysis, for NeuPSIG, IASP (Edit comment: Bennett DL; ) Previous iterations: Pain December 2007, Arch Neurol November 2003,

62 MEDICATION MANAGEMENT Lancet Neurology, Feb 2015; MAIN CONCLUSION (page 169) Based mainly on moderate or high quality of evidence and efficacy in most trials, TCAs, gabapentinoids, & SNRIs, are recommended for use in neuropathic pain, and are proposed as first-line treatments

63 Strong Recommendations 1 st -Line Dose (mg/day) NNT Tricyclic ADs Nortriptyline (fewer side-effects than amitriptyline) Gabapentin Pregabalin Duloxetine Venlafaxine Ie, 3 classes of 1 st -line pharmacotherapy for NP: TCAs, gabapentinoids, SNRIs

64 Weak Recommendations 2 nd -Line Dose (mg/day) NNT Capsaicin 8% patch 10.6 (PNP) (30-60 mins every 3 months) Lignocaine 5% patch (PNP) (Max: 3 patches, up to 12 hours/day) (Demoted from 1 st -line due to weak quality of evidence ) Tramadol

65 Weak Recommendations 3 rd -Line Dose (mg/day) NNT Strong Opioids SR 180 mg Meq 4.3 individual titration (13 trials in PNP used oxycodone or morphine; 10/13 +ve; max effectiveness 180mg morphine equivalent) (demoted from 1 st or 2 nd line abuse potential, & deaths, etc) Botulinum A units 1.9* (PNP) (Sub-cut every 3 months) (*4 small RCTs; but one large unpublished RCT ve)

66 Inconclusive recommendations (discrepant Combination therapy Capsaicin cream Carbamazepine Clonidine topical Lacosamide Lamotrigine NMDA antagonists (eg, ketamine) Oxcarbazepine SSRI antidepressants Tapentadol Topiramate Zonisamide findings)

67 Recommendations against use: (Negative Trials &/or Safety Concerns) 1. Weak recommendations against use: Cannabinoids ( negative results, potential misuse, diversion, & long-term mental health risks ) Valproate 2. Strong recommendations against use: Levetiracetam Mexiletine

68 Other comments No RCTs of NSAIDs or paracetamol in NP (Or bisphosphonates, or (oral) clonidine? not mentioned) efficacy of systemic drug treatments is generally independent of aetiology of underlying disorder generally no evidence of efficacy of particular drugs in specific disorders recommendations apply to neuropathic pain in general might not be applicable to trigeminal neuralgia only 1 x RCT meeting inclusion criteria ( see Review, BMJ )

69 No Evidence in Neuropathic Pain for: Anti-inflammatories Vo, T et al: Topical review: Non-steroidal antiinflammatory drugs for neuropathic pain: How do we explain continued widespread use? Pain; 143 (2009) Paracetamol NB: WHO Analgesic Ladder does not apply to chronic non-malignant pain, including neuropathic pain.

70 Other comments Publication Bias previous meta-analyses overestimated Effect Sizes by about 10% for individual drugs NNT for 50% pain relief ranging from about 4 to 10 for most positive trials emphasise the modest overall study outcomes Inadequate response to drug therapy constitutes a substantial unmet need & might have important consequences in terms of psychological or social adjustment

71 Treatment of Chronic Pain Summary For both Neuropathic Pain & Dysfunctional Pain: Pharmacological TCAs (nortriptyline, a secondary amine). Titrate to therapeutic dose (plasma range: nmol/l) Gabapentin / Pregabalin SSNRIs (venlafaxine) Non-Pharmacological: Graduated aerobic Exercise CBT

72 OPIOIDS RECENT EDITORIALS 1 There is a striking global inequity in access to opioid analgesics. In 2008, the 13% of the world s population living in Australia, Canada, New Zealand, the USA, and the member states of the European Union, consumed more than 90% of the morphine consumed globally Liberman J et al: Ending inequities in access to effective pain relief? ; Lancet, 11 September 2010, page 856-7

73 OPIOIDS RECENT EDITORIALS 2 Gaps exist in the literature on both the effectiveness and the harms of long-term use of opioids for chronic musculoskeletal and non-cancer pain, and in the long term they may actually be ineffective... the clinical community must ask itself why, in the face of inadequate evidence of effectiveness, and emerging evidence of potential harms, such an increase in the prescription of opioids for chronic non-cancer pain has occurred?... the evidence of potential risks of long-term opioid use, combined with the lack of evidence of effectiveness, is a public health concern, given the high prevalence of chronic musculoskeletal pain and the rising trends in opioid use. Dunn KM, Hay EM: Opioids for chronic musculoskeletal pain: lack of evidence of benefit & potential for harm should caution against their use ; BMJ, 4 September 2010, Vol 341, pp

74 OPIOIDS RECENT EDITORIALS 3 Although I am still convinced that the principles of pain management (with opioids) that I have followed are correct for patients with cancer or other painful lifethreatening diseases, and for the short-term management of painful conditions (eg, sickle cell crisis, kidney stones), I have come to question whether the long-term treatment of non-malignant pain (with opioids) is causing more harm than good. Four things can be said with certainty. First, the use of opioid treatment for nonmalignant conditions has grown during the last 2 decades. Second, with the increase in the use of opioid treatment for non-malignant pain, there has also been an increase in the number of deaths due to opioid overdose. Third, long-term opioid use is associated with a number of adverse consequences in addition to overdose, including decreased cognitive function, constipation, hyperesthesias (increased pain due to the use of opioids), immune suppression, hormonal changes, addiction, and diversion of medication... Fourth, although it is clear that opioids relieve short-term pain, there is no evidence from randomized controlled studies indicating that they are effective in the long-term treatment of chronic pain. Suddenly, I find myself to be a believer who has lost his faith. Katz MH: Long-term Opioid Treatment of Nonmalignant Pain: a Believer Loses His Faith ; Arch Intern Med, 13/09/10, pp

75 OPIOIDS RECENT EDITORIALS 4 Opioid prescribing in the U.S. increased 200- fold over a single decade, largely because of new prescribing for chronic pain. Ballantyne, J: Is Lack of Evidence the Problem? The Journal of Pain, September 2010: pp ;

76 OPIOIDS RECENT EDITORIALS 5 In the United States, the 2009 National Survey on Drug Use & Health documented that 8.7% of individuals older than 12 years reported past month illicit drug use.... While historically heroin has been most commonly abused, nonmedical use of prescription opioid pain relievers is now the dominant form of opioid abuse in the United States. In 2009, more than 5.3 million Americans reported past month prescription opioid abuse, and the 2009 Monitoring the Future Study demonstrated that among 12thgraders, 9.7% reported abuse of hydrocodone and 4.9% reported abuse of oxycodone in the past year. Thus, illicit opioid use is a critical national health issue that requires creative approaches to prevention and treatment. O Connor PG: Advances in the Treatment of Opioid Dependence: Continued Progress & Ongoing Challenges ; JAMA, 13 October 2010, pp

77 Guidelines for Opioid Prescription: The Devil Is in the Details. Ann Int Med, ; page 843 More people in the United States now die of prescription drug overdose than accidental vehicular trauma. This startling statistic has stimulated physicians, government agencies, and various organizations to effect change through provider guidelines, patient education, and proactive legislation. Opioid analgesics, particularly oxycodone, are major contributors to this trend in preventable death.

78 Opioid Analgesics Risky Drugs, Not Risky Patients JAMA, , page 2219 From 1999 to 2010 the number of people in the United States dying annually from opioid analgesicrelated overdoses quadrupled, from 4030 to 16,651. Patients predisposition to overdose could not have changed substantially in that time; what has changed substantially is their exposure to opioids. During this same time, the amount of opioids prescribed also quadrupled.

79 Opioids The use of added short-acting opioids for breakthrough pain ( rescue dosing) is controversial. Although occasionally taking an extra pill for a pain spike is unlikely to harm, too many patients end up with daily or near-daily use of rescue opioids, obviating their purpose, and encouraging tolerance to what is effectively a higher daily dose. R. Norman Harden et al: Special Article. Complex Regional Pain Syndrome: Practical Diagnostic & Treatment Guidelines, 4 th Edition ; Pain Medicine 2013; 14: Burwood Hospital PMC Opioid Guidelines (1999): 1. Generally don t use strong opioids in CNMP 2. If we do, it is normally methadone 3. We do not use strong opioids in CNMP pts with co-morbid addiction ( dual pathology ) 4. We do not give an opioid script at the first appointment. We do so only after discussion with colleagues, eg at weekly case conference.

80 Opioid Contract Consider a signed opioid contract with the patient: 1. It is a trial if it is not effective, it will be stopped. Starting a patient on morphine does not morally oblige us to continue it: 2. Patients don t tell us what drug, & how many mg, to prescribe the law specifies that that is our job. 3. Evidence of diversion / abuse stop 4. Effectiveness normally needs an objective measure, eg improved function. Eg a patient reporting that their pain is much better, but it s not good enough yet, because I m still in agony & disabled by pain. So I need more is not evidence of efficacy, & thus not grounds for perpetual dose escalation mg Morphine Equivalent / day will not be exceeded risks, & lack of efficacy 6. No replacements for lost, eaten, stolen, or transmigrated scripts. 7. Random Urine Drug Screens to see what is, & isn t, present 8. One prescriber, one dispensing pharmacy

81 Fallacies, often implicit / sub-conscious, driving opioid prescribing & escalation: If all else fails, use morphine because: 1. It is our strongest analgesic, our gold standard. Wrong: it is the gold standard for severe nociceptive or inflammatory pain (eg, postop, post-traumatic), & for terminal malignant pain. But, as we have seen, it is not the gold standard for neurogenic pain. 2. Related to the above it must be nociceptive or inflammatory pain, so morphine must be effective, because the nociceptive system, alone of bodily organ systems, is infallible (except neuropathic pain). Nociceptive exceptionalism nociceptive fundamentalism. Wrong: the nociceptive system is not an exception; but, like every other organ system, it can also malfunction, mislead; so it must not always be read literally (fundamentalism). Primary pain disorders Eg, CRPS-1; primary headaches (migraine): in these cases, pasin does not = severe & life-threatening intra-cranial pathology. The pain is misleading. A malfunctioning fire alarm, not a fire. 3. The Fairy-Tale Fallacy ( they all lived happily ever after ): There must be a fix. Wrong: Need to grapple with the Problem of Evil.