TREATMENT FOR LOW BACK PAIN: What Does Science Say Systematic Reviews of Common Chronic pain Medications and Intervent

1. TREATMENT FOR LOW BACK PAIN: What Does Science Say??Systematic Reviews of Common Chronic pain Medications and Interventions Trang Nguyen MD, PhD, FAADEP David C Randolph, MD, MPH, FAADEP October 14, 2011 LWCC, New Orleans, LA. 1

2. Many Thanks to: Lloyd Colvin Please note we have provided a number of references for you here today. If you have trouble getting these and need help, please ask Mr. Colvin and we will see to it a PDF is provided Marjorie Eskay-Auerbach, MD, JD. For her expert assistance in material preparation. 2

3. A few facts about LBP: Mostly a self limited phenomenon Definitions: Sprain, Strain, �Sprain/Strain� Historic information of paramount importance for determining likely source of pain Nothing takes the place of a good history and physical exam 3

4. 4 NON-SPECIFIC LOW BACK PAIN

5. Occurrence LBP is the 5th most common reason for physician visits in the US � of US adults report low back pain lasting 1 day in the last 3 months 7.6% report at least 1 episode of severe LBP within a 1 year period Significant costs 5

6. NSLBP Presentation Low back pain is pain, muscle tension, or stiffness, localized below the costal margin and above the inferior gluteal folds. Acute < 12 weeks Chronic > 12 weeks Affects 70% of people in resource-rich countries at some point 6

7. Natural History Many patients have self-limited episodes and do not seek care Among those who seek medical care, pain, disability and RTW typically improve rapidly in the first month Pengel LH, Herbert RD, Maher CG, Refshauge KM. Acute low back pain: systematic review of its prognosis. BMJ. 2003;327:323 Up to one third of patients report persistent back pain of at least moderate intensity 1 year after an acute episode, and 1 in 5 report substantial limitations in activity Von Korff M, Saunders K. The course of back pain in primary care. Spine. 1996;21:2833-7; discussion 2838-9 7

8. Classification � Initial Triage Focused History and Physical to identify: Non-specific low back pain (NSLBP) LBP associated with radiculopathy or spinal stenosis LBP associated with another specific spinal cause Assessment of psychosocial risk factors that predict risk for chronic disability low back pain No evidence suggests that labeling most patients with low back pain by using specific anatomical diagnoses improves outcomes (ACP/APS) 8

9. NSLBP Is Not - Diagnosis In patients with back and leg pain, a typical history for sciatica (back and leg pain in a typical lumbar nerve root distribution) has a fairly high sensitivity but uncertain specificity for herniated disc van den Hoogen HM, Koes BW, van Eijk JT, Bouter LM. On the accuracy of history, physical examination, and erythrocyte sedimentation rate in diagnosing low back pain in general practice. A criteria-based review of the literature. Spine. 1995;20:318-27. [PMID: 7732468] Vroomen PC, de Krom MC, Knottnerus JA. Diagnostic value of history and physical examination in patients suspected of sciatica due to disc herniation: a systematic review. J Neurol. 1999;246:899-906. 9

10. NSLBP Is Not - Diagnosis Positive SLR (defined as reproduction of the patient's sciatica between 30 and 70 degrees of leg elevation) relatively high sensitivity (91% [95% CI, 82% to 94%]) modest specificity (26% [CI, 16% to 38%]) for diagnosing herniated disc Devill� WL, van der Windt DA, Dzaferagic A, Bezemer PD, Bouter LM. The test of Las�gue: systematic review of the accuracy in diagnosing herniated discs. Spine. 2000;25:1140-7 By contrast, the crossed straight-leg-raise test is more specific (88% [CI, 86% to 90%]) less sensitive (29% [CI, 24% to 34%]). 10

11. NSLBP Is Not - Diagnosis Evidence on the utility of history and examination for identifying lumbar spinal stenosis is sparse High-quality studies modest or poor positive likelihood ratios (1.2 for pseudoclaudication and 2.2 for radiating leg pain). Changing symptoms on downhill treadmill testing are associated with the highest positive likelihood ratio (3.1). Age older than 65 years was associated with a positive likelihood ratio of Other findings have only been evaluated in lower-quality studies or are poorly predictive for lumbar spinal stenosis. 11

12. Clinician must be satisfied that there is no specific cause 12

13. Psychosocial Factors Evidence is currently insufficient to recommend optimal methods for assessing psychosocial factors and emotional distress. Psychosocial factors that may predict poorer low back pain outcomes include presence of depression, passive coping strategies, job dissatisfaction, higher disability levels, disputed compensation claims, or somatization Pincus T, Burton AK, Vogel S, Field AP. A systematic review of psychological factors as predictors of chronicity/disability in prospective cohorts of low back pain. Spine. 2002;27:E109-20 Steenstra IA, Verbeek JH, Heymans MW, Bongers PM. Prognostic factors for duration of sick leave in patients sick listed with acute low back pain: a systematic review of the literature. Occup Environ Med. 2005;62:851-60 13

14. Imaging ACP/ACS Clinicians should not routinely obtain imaging or other diagnostic tests in patients with nonspecific low back pain (strong recommendation, moderate-quality evidence). Plain radiography is recommended for initial evaluation of possible vertebral compression fracture in selected higher-risk patients, such as those with a history of osteoporosis or steroid use Jarvik JG, Deyo RA. Diagnostic evaluation of low back pain with emphasis on imaging. Ann Intern Med. 2002;137:586-97 14

15. Imaging ACP/ACS Evidence to guide optimal imaging strategies is not available for low back pain that persists for more than 1 to 2 months despite standard therapies if there are no symptoms suggesting radiculopathy or spinal stenosis, 15

16. Imaging ACP/ACS Prompt work-up with MRI or CT is recommended in patients who have severe or progressive neurologic deficits or are suspected of having a serious underlying condition (such as vertebral infection, the cauda equina syndrome, or cancer with impending spinal cord compression) because delayed diagnosis and treatment are associated with poorer outcomes 16

17. Imaging ACP/APS Magnetic resonance imaging is generally preferred over CT if available because it does not use ionizing radiation and provides better visualization of soft tissue, vertebral marrow, and the spinal canal Magnetic resonance imaging (preferred if available) or CT is recommended for evaluating patients with persistent back and leg pain who are potential candidates for invasive interventions �plain radiography cannot visualize discs or accurately evaluate the degree of spinal stenosis Jarvik JG, Deyo RA. Diagnostic evaluation of low back pain with emphasis on imaging. Ann Intern Med. 2002;137:586-97 17

18. Do medical interventionsmake a difference in outcomes??? 18

19. Long acting opioids: Pain & Function Systemic review of 16 randomized controlled trials and 8 observational studies studying efficacy and safety of long-acting opioids in CNCP n=2617 Studies examined the use of long-acting opioids (taken = twice a day) in CNCP patients �transdermal fentanyl and long acting oral oxycodone, morphine, codeine, and dihydrocodeine Efficacy regarding reducing pain and improve function Adverse Effects Subgroup analysis- which long acting opioid is more effective Chou R, et al. J Pain and Symptom Management.2003; 26:1026-1048 19

20. Long acting opioids: Pain & Function Different studies used different assessments for pain intensity Visual Analogue Scale (VAS): scale of 0-100 for no pain to severe pain. Categorical Pain Scale No scale Only one study assessed quality of life with SF-36 Loss to follow up Lack of adequate blinding Chou R, et al. J Pain and Symptom Management.2003; 26:1026-1048; Systematic Review Article 20

21. Long acting opioids: Pain & Function Conclusions: Comparing 1 long acting opioid to another long acting opioid (2 trials) Insufficient evidence from head to head comparison studies. Comparing long acting opioids to other types of drugs or placebo (14 trials- mostly placebo, one trial with Darvocet, one trial with Cogentin) There is insufficient evidence to suggest that long-acting opioid is superior to another in terms of efficacy. Pain scales varied between trials. Comparing long acting opioids to short acting opioids in improving pain and function (7 trials) There is insufficient evidence Chou R, et al. J Pain and Symptom Management.2003; 26:1026-1048; Review Article 21

22. Efficacy: Oral Opioids Meta-analysis of 11 randomized, placebo controlled trials comparing oral opioids to placebo n=1025 Length 4 days-8 weeks 388/1025 (38%) had open label f/u beyond 8 weeks Only 170 (44%) were on opioids after therapy for 7-24 months Kalso E, et al. Pain. 2004: 372-380. Systematic Review 22

23. Studies Oral Opioids Calwell-1999 OA Oxycodone 40mg /day 4 weeks Caldwell- 2002 OA Morphine 30mg/day 4 weeks Gimbell 2003 DN Oxycodone 42mg/day 4weeks Harke 2001 PNP Morphine 83mg/day 8 days Huse 2001 Phantom Limb Pain Morphine 120mg/day 4 weeks Maier 2002 Mixed types Pain Morphine 114mg 4 days Moulin 1996 MSK pain Morphine 83.5mg 6 weeks Raja 2002 Post Herpetic Neuralgia Morphone 91mg/day and Methadone 15mg/day 8 weeks Roth 2000 OA Oxycodone 20mg or 40mg/day 2 weeks 23

24. Studies Oral Opioids Watson 1998 Post Herpetic Neuralgia Oxycodone 45mg/day 4 weeks Watson 2003 DN Oxycodone 40mg 4 weeks Kalso E, et al. Pain. 2004: 372-380. Systemic Review 24

25. Function: Oral Opioids Function 5/11 studies reported no significant difference in either self reported overall activity or ADL 1/11 reported improved in disability (Maier, 2002) 2/11 reported lower disability scores during treatment (Watson 1998 and 2003) Kalso E, et al. Pain. 2004: 372-380. Systemic Review 25

26. Efficacy: Oral Opioids Mean decrease in pain intensity in most studies was at least 30% with the use of opioids compare to placebo Effectiveness was comparable in neuropathic and nociceptive pain However� Tolerance: occurred in 6% patients at one year. Most patients required increased doses of opioids Lower doses (Morphine 30 mg and Oxycodone 20 mg PO qd) were not effective Side effects prevented from increasing dose Only 3/11 trials used a validated quality of life questionnaire (SF-36 or Sickness Impact Profile) Only 1/11 reported a + difference in quality of life with opioids We don�t know if opioids improved quality of life Kalso E, et al. Pain. 2004: 372-380. Systemic Review 26

27. Opioids -Efficacy Furlan A. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ. May 23,2006. 174(11) p. 1589-94. Meta-analysis Methods: Literature search up to May 2005 Results Total- 6019 patients with CNCP 80% nociceptive pain, 12% neuropathic & others Ages � 40-71 years; average 58 years 63% female and 85% white Duration of therapy 1 week to 16 weeks 27

28. Results 90% of the studies funded or had > 1 author affiliated with pharmaceutical industry. 17/41 RCTs have adequate randomization 30/39 trials have adequate �double-blinded� Drop out rate 33% - 38% (cases & controls- side effects or inadequate pain relief) Not all RCTs have adequate data for meta-analysis 28

29. Efficacy- Pain relief Opioids vs. PLACEBO 28 RCTs data available for meta-analysis Results in favor of opioids SMD -0.60, 95% CI -0.69 to -0.50 Standard mean difference SMD = Mean (case) � Mean (controls) pooled standard deviation Conclusion persist with subgroup analysis of different opioids and methodological quality 29

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31. Efficacy- functional outcomes Opioids vs. PLACEBO 20 RCTs Results favor opioids SMD -0.31, 95% CI -0.41 to -0.22 Subgroup analysis Long acting morphine compared to placebo was not statistically significant Mixed pain subjects also do not have statistically significant functional relief with opioids 31

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33. Efficacy- Pain relief Opioids vs. other ANALGESICS 8 RCTs Pain relief NOT statistically significant SMD � 0.05, 95% CI -0.32 to 0.21 Subgroup analysis did not change conclusions NSAIDs, TCAs or methodological quality Strong opioids (oxycodone and morphine) compared to NSAIDs or TCAs Subgroup analysis was significant for pain relief SMD- 0.34, 95% CI -0.67 to -0.01) 33

34. Efficacy- Pain relief 34

35. Efficacy- functional outcomes Opioids vs. other analgesics Other analgesics more effective SMD 0.16, 95% CI 0.03 to 0.30 35

36. Efficacy- functional outcomes 36

37. Efficacy Martell B. �Systematic Review: Opioid Treatment for Chronic Back Pain: Prevalence, Efficacy, and Association with Addiction� Ann Intern Med. 2007; 146: 116-27. Meta-analysis Methods Literature search up to March 2005 Chronic low back pain (> 3 months) Oral, topical or transdermal opioids 37

38. Efficacy Results 18 studies 15 studies for final analysis- 3 excluded quality score poor 1008 patients 8/15 studies used randomized, double blind trial 4/15 studies had placebo controlled 11/15 trials sponsored by pharmaceutical companies 38

39. Efficacy- Pain relief Results Opioids vs. Nonopioids or Placebo 4 RCTs- quality score �excellent� Study duration- mean 64 days (7-16 weeks) Patient retention- 67%-99% Average morphine dose- 73mg/day (30-232mg/day) (most trials do not have pretrial analgesia) Nonsignificant pooled data 39

40.  Efficacy- Opioids vs. nonopioids or Placebo 40

41. Efficacy- Pain relief Opioids vs. other Opioids 5 RCTs for meta-analysis SMD- -0.93; 95% CI -1.89 to -0.03; P = 0.055 Nonsignificant reduction in pain Sensitivity analysis- (randomized vs. non-randomized, study duration, study quality, sample size and dosages) did not change the conclusion 41

42. Efficacy- vs. other opioids 42

43. Efficacy- Pain relief Conclusions: Meta-analysis (opioids vs. nonopioids or placebo) no significant effect SMD- -0.199; 95% CI -0.49 to 0.11; P= 0.136 Sensitivity analysis- (study quality, sample size, study duration, and opioid dose) did not change SMD Not more effective compared to other analgesics (NSAIDs or TCA) Opioids have limited efficacy in treatment of CLBP 43

44. Conclusions Efficacy Comparing one opioids to another opioids- no significant effect 44

45. Conclusions Problems Short term follow up (max 16 weeks) Study design- lack of information on follow up Small sample size Array of diagnostic criteria Various functional outcome and pain score measurements Improvement in pain not equivalent of function No objective correlation 45

46. Opioids Opioids in the Management of Chronic Non-Cancer Pain: An Update of American Society of the Interventional Pain Physicians� (ASIPP) Guidelines Pain Physician 2008: Opioids Special Issue: 11:S5-S62. 46

47. Summary of Evidence- Opioid Effectiveness Based on the review of multiple systematic reviews and the available literature, the evidence for the effectiveness of long-term opioids (specifically transdermal Fentanyl and sustain release morphine) in reducing pain and improving the functional status for 6 months or longer is available but weak. Noble M. J. Pain Symptom Manage 2008; 35:214-228. Systematic Review. Trescot AM. Pain Physician 2008; 11: S181-S200. 47

48. Opioids For Oxycodone, the level of evidence is limited. For Hydrocodone and Methadone, the level of evidence is non-existent (opinions- no published evidence regarding effectiveness with long term therapy) 48

49. Hydrocodone There were no studies evaluating the effectiveness of hydrocodone even though this is the most commonly used drug. 49

50. RecommendationsOpioids Based on the review of multiple systematic reviews and the available literature, there is insufficient data for long term opioids with regards to efficacy and improve function. Patients withdrew from clinical trials secondary to side effects (32% for oral therapy, 17% for transdermal) and insufficient pain relief (12% oral therapy and 5% transdermal) Substantial heterogeneity among oral studies Many trials have removal of patients who do not respond leading to high drop out rate. Validity of the trials is questionable. 50

51. Opioid Therapy G u i d e l i n e f o r t he Use of Chronic Opioid Therapy in Chronic Noncancer Pain-Evidence Review The American Pain Society in Conjunction with the American Academy of Pain Medicine February 2009 Recommended Reading*** 51

52. Opioid Therapy Criteria Chronic non-cancer pain Opioid- oral, transdermal, buccal, rectal, IM or SQ routes IV and Intrathecal or Intraspinal routes excluded Systematic reviews, RCTs, and Cohort Studies See study for details 52

53. Comparing Long Acting Opioids There is insufficient evidence from eight head-to-head trials (three higher-quality) and three observational studies to conclude that any long-acting opioid (sustained-release formulation or transdermal fentanyl) is more beneficial or less harmful than others. Level of evidence: moderate 53

54. Comparing sustained-release andimmediate-release formulations of opioids Seven trials (two higher-quality) found no clear differences in benefits or harms between sustained- and immediate-release opioids (level of evidence: high). Chou, 2003 systematic review. 54

55. Comparisons between different Tramadols Six trials (three higher-quality) found no clear differences in benefits or harms between extended-release (once/day), sustained-release (twice/day), and immediate release Tramadol (level of evidence: high). 55

56. Comparisons between Tramadol versus opioids Three trials (one higher-quality) found no clear difference in efficacy between tramadol and different opioids. (level of evidence: moderate). Evidence of differences in harms was inconclusive. Jensen, 1994- OA- f/u 2 weeks, n= 264 *Mullican, 2001- OA or LBP- f/u 22 days, n= 462 Wilder-Smith, 2001- OA- f/u 1month, n= 57 56

57. Pharmacologic Management for Chronic Non-Cancer Pain Practice Guidelines for Chronic Pain Management An Updated Report by the American Society of Anesthesiologists (ASA) Task Force on Chronic Pain Management and the American Society of Regional Anesthesia and Pain Medicine (ASRA) April 2010 57

58. Opioid therapy A meta-analysis of randomized controlled trials indicates that controlled or extended release opioid therapy (e.g., morphine, codeine, and oxycodone) provides effective pain relief for patients with low back pain or neuropathic pain for assessment periods ranging from 1 to 9 weeks, with nausea or vomiting and constipation as side effects (Category A1 evidence). 58

59. Opioid therapy Randomized controlled trials indicate that Tramadol provides effective pain relief for assessment periods ranging from 4 to 6 weeks (Category A2 evidence). 59

60. Opioid therapy Studies with observational findings report that immediate release opioids, transdermal opioids, and sublingual opioids provide relief for back, neck, leg, and neuropathic pain for assessment periods ranging from 2 weeks to 3 months (Category B2 evidence). 60

61. Opioid therapy ASA and ASRA members agree and consultants are equivocal as to whether opioids should be used for patients with neuropathic or back pain. CAUTION: REFERENCES ARE NOT AVAILABLE FOR REVIEW Reference 1. American Society of Anesthesiologists: Practice guidelines for chronic pain management. ANESTHESIOLOGY 1997; 86:995�1004 61

62. Update on guidelines for the treatment of chronic musculoskeletal pain 2006 American College of Rheumatology (ACR) European League Against Rheumatism (EULAR) American Pain Society (APS) 62

63. Moderate to Severe LBP Nociceptive +/� neuropathic pain Long term Elderly Weak opioid combinations: Paracetamol (Tylenol)/tramadol* Tramadol* Strong opioids *Tramadol is efficacious for both nociceptive and neuropathic pain 63

64. Moderate to Severe LBP Nociceptive +/� neuropathic pain Long term Young/Healthy COX-2 inhibitors/NSAIDs (low dose) +/or paracetamol/tramadol* (NSAID-sparing) Tramadol* Strong opioids *Tramadol is efficacious for both nociceptive and neuropathic pain 64

65. Therapeutic options for treating moderate-to-severe pain following injury Pain intensity (moderate to severe) 1. Non-selective NSAID (anti-inflammatory dose) 2. +/� Paracetamol (full therapeutic dose) 3. +/� Opioid combination 4. +/� Tramadol (full therapeutic dose) 5. Strong opioids 65

66. Therapeutic options for treating moderate-to-severe pain following injury Immediate Surgery Do not use NSAIDs and start with: COX-2 inhibitor +/or opioid combination +/or opioid (weak�strong) 66

67. Therapeutic options for treating moderate-to-severe pain following injury If surgery considered: Stop NSAID 5 half-lives before operation and substitute with: COX-2 inhibitor +/or opioid combination +/or opioid (weak�strong) 67

68. Therapeutic options -supporting rehabilitation Moderate to Severe Pain- (constant) Paracetamol +/or opioid combination +/or weak opioid/ tramadol sustained release +/or strong opioid sustained release 68

69. Therapeutic options-supporting rehabilitation Moderate to Severe Pain- Pain in motion/ inflammatory* NSAID/COX-2 inhibitors for 3�5 days Short-acting PRN opioid combination Weak opioid/tramadol immediate release Strong opioid immediate release *Depending on co-morbidities 69

70. Anticonvulsants Cochrane Review- 2009, Issue 4 RCTs only Trigeminal neuralgia, post herpetic, diabetic neuropathy, central pain post stroke, IBS, TMJ dysfunction Mostly oral medication Carbamazepine Clonazepam Gabapentin Phenytoin Sodium Valproate 70

71. Anticonvulsants Results: 23 trials of 6 anticonvulsants Acute pain- one trail � placebo vs. sodium valproate- no evidence of effectiveness 71

72. Anticonvulsants Chronic Pain- anti-convulsant is not first line medication (except for trigeminal neuralgia). Trigeminal Neuralgia 3 trials of carbamazepine- NNT for effectiveness of 2.5 Post Herpetic Neuralgia 1 trial of Gabapentin � NNT 3.2 Diabetic Neuropathy (1 trial each) Carbamazepine- NNT 2.3 Gabapentin � NNT 3.8 Phenytoin � NNT 2.1 72

73. Antidepressants Meta-analyses of randomized controlled trials indicate that tricyclic antidepressants provide effective pain relief for a variety of chronic pain etiologies for assessment periods ranging from 2 to 8 weeks (Category A1 evidence). In addition, meta-analyses of randomized controlled trials indicate that selective serotonin�norepinephrine reuptake inhibitors provide effective pain relief for a variety of chronic pain etiologies for assessment periods ranging from 3 to 6 months (Category A1 evidence). A meta-analysis of randomized placebo-controlled trials is equivocal regarding the efficacy of selective serotonin reuptake inhibitors in providing effective pain relief for diabetic neuropathy (Category C1 evidence). 73

74. Antidepressants Consultants, ASA members, and ASRA members strongly agree that tricyclic antidepressants should be used. ASA members and ASRA members agree and consultants strongly agree that serotonin-norepinephrine reuptake inhibitors should be used. 74

75. Benzodiazepines: One case report indicates that benzodiazepines can provide pain relief for up to 2 months for neuralgic pain syndrome (Category B3 evidence). Consultants and ASRA members disagree and ASA members are equivocal with regard to whether benzodiazepines should be used for chronic pain. 75

76. Skeletal muscle relaxants The literature is insufficient to evaluate the efficacy of skeletal muscle relaxants in providing pain relief for patients with chronic pain (Category D evidence). ASA members and ASRA members agree and consultants are equivocal with regard to whether skeletal muscle relaxants should be used for patients with chronic pain. 76

77. NSAIDs Randomized controlled trials indicate that NSAIDs compared with placebo provide effective pain relief for patients with back pain for assessment periods ranging from 2 to 12 weeks (Category A2 evidence). Consultants, ASA members, and ASRA members agree that NSAIDs should be used for patients with back pain. 77

78. Topical agents Randomized, placebo-controlled controlled trials of topical agents (e.g., capsaicin, lidocaine, and ketamine) are equivocal regarding relief of peripheral pain for patients with neuropathic pain (e.g., diabetic neuropathy and postherpetic neuralgia) (Category C2 evidence). 78

79. Topical agents Studies with observational findings indicate that topical agents (e.g., capsaicin,lidocaine, and ketamine) provide relief for peripheral neuropathic pain for assessment periods ranging from 3 to 6 weeks (Category B2 evidence). 79

80. Topical agents Consultants, ASA members, and ASRA members agree that topical agents should be used for patients with peripheral neuropathic pain. 80

81. Summary Anticonvulsants: Anticonvulsants (e.g., -2-delta calcium-channel antagonists, sodium-channel antagonists, and membrane-stabilizing drugs) should be used as part of a multimodal strategy for patients with neuropathic pain. 81

82. Summary Antidepressants: Tricyclic antidepressants and serotonin�norepinephrine reuptake inhibitors should be used as part of a multimodal strategy for a variety of patients with chronic pain. Selective serotonin reuptake inhibitors may be considered specifically for patients with diabetic neuropathy. 82

83. Summary As part of a multimodal pain management strategy, extended-release oral opioids should be used for neuropathic or back pain patients, and transdermal, sublingual, and immediate-release oral opioids may be used. 83

84. Summary A strategy for monitoring and managing side effects, adverse effects, and compliance should be in place BEFORE prescribing any long-term pharmacologic therapy. 84

85. Treatment of Neuropathic Pain Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update- March 2010 Treatment of Neuropathic Pain: An Overview of Recent Guidelines October 2009 85

86. Treatment of Neuropathic Pain Comparison of Neuropathic Pain Treatment Guidelines, Excluding Trigeminal Neuralgia* Postherpetic neuralgia; painful polyneuropathy; Central pain Medication Class NeuPSIG CPS EFNS Tricyclic First line First line First line (Nortriptyline (Pamelor) or Desipramine (Norpramin)) CPS Canadian Pain Society; EFNS European Federation of Neurological Societies; NeuPSIG Neuropathic Pain Special Interest Group (International Association for the Study of Pain); 86

87. Treatment of Neuropathic Pain Comparison of Neuropathic Pain Treatment Guidelines, Excluding Trigeminal Neuralgia* Postherpetic neuralgia; painful polyneuropathy; Central pain Medication Class NeuPSIG CPS EFNS Ca. Channel ligands First line First line First line (Gabapentin (Neurontin) and Pregablin (Lyrica)) CPS Canadian Pain Society; EFNS European Federation of Neurological Societies; NeuPSIG Neuropathic Pain Special Interest Group; 87

88. Treatment of Neuropathic Pain Comparison of Neuropathic Pain Treatment Guidelines, Excluding Trigeminal Neuralgia* Painful polyneuropathy Medication Class NeuPSIG CPS EFNS SSNRIs First line Second line Second line (Cymbalta, Effexor) CPS Canadian Pain Society; EFNS European Federation of Neurological Societies; NeuPSIG Neuropathic Pain Special Interest Group; 88

89. Treatment of Neuropathic Pain Comparison of Neuropathic Pain Treatment Guidelines, Excluding Trigeminal Neuralgia* Neuropathic pain Medication Class NeuPSIG CPS EFNS Topical Lidocaine First line Second line First line 5% patch Localized peripheral NP PHN/allodynia CPS Canadian Pain Society; EFNS European Federation of Neurological Societies; NeuPSIG Neuropathic Pain Special Interest Group; 89

90. Treatment of Neuropathic Pain Third Line Medications Anti-depressant Medications Bupropion (Wellbutrin), Citalopram (Celexa), Paroxetine (Paxil) Anti-epileptic Medications Carbamazepine (Tegretol), Lamotrigine (Lamictal) Oxcarbazepine (Trileptal), Topiramate (Topamax), Valproic Acid (Depakote) Topicals Capsaicin 90

91. Treatment of Neuropathic Pain Reassess pain and health-related quality of life frequently If substantial pain relief (e.g., average pain reduced to NRS <3/10) and tolerable side effects, continue treatment. If partial pain relief (e.g., average pain remains NRS >4/10) after an adequate trial, add 1 of the other first-line medications If no or inadequate pain relief (e.g., <30% reduction) at target dosage after an adequate trial, switch to an alternative first-line medication. If trials of first-line medications alone and in combination fail, consider second and third line medications or referral to a pain specialist or multidisciplinary pain center 91

92. Treatment of Neuropathic Pain See Tables for the following: Starting dose Titration Maximum Dosage Duration of Adequate Trial Major side effects Precautions Other Benefits 92

93. Opioids for Chronic Non-Cancer Pain Guidelines for outpatient prescription of oral opioids for injured workers with chronic, noncancer pain. Washington State Department of Labor and Industries. Guidelines for outpatient prescription of oral opioids for injured workers with chronic, noncancer pain. Olympia (WA): Washington State Department of Labor and Industries; 2002 Aug. 21 p. [28 references] 93 Nociceptive pain Nociceptors are the nerves which sense and respond to parts of the body which suffer from damage. They signal tissue irritation, impending injury, or actual injury. When activated, they transmit pain signals (via the peripheral nerves as well as the spinal cord) to the brain. The pain is typically well localized, constant, and often with an aching or throbbing quality. Examples include sprains, bone fractures, burns, bumps, bruises, inflammation (from an infection or arthritic disorder), obstructions, and myofascial pain (which may indicate abnormal Visceral pain is the subtype of nociceptive pain that involves the internal organs. It tends to be episodic and poorly localized. Nociceptive pain is usually time limited, meaning when the tissue damage heals, the pain typically resolves. Neuropathic pain Neuropathic pain is the result of an injury or malfunction in the peripheral or central nervous system. The pain is often triggered by an injury, but this injury may or may not involve actual damage to the nervous system. Nerves can be infiltrated or compressed by tumors, strangulated by scar tissue, or inflamed by infection. The pain frequently has burning, lancinating, or electric shock qualities. Persistent allodynia, pain resulting from a nonpainful stimulus such as a light touch, is also a common characteristic of neuropathic pain. The pain may persist for months or years beyond the apparent healing of any damaged tissues. In this setting, pain signals no longer represent an alarm about ongoing or impending injury, instead the alarm system itself is malfunctioning. Examples include post herpetic neuralgia, reflex sympathetic dystrophy, components of cancer pain, phantom limb pain, carpal tunnel syndrome, and peripheral neuropathy. Among the many causes of peripheral neuropathy, diabetes is the most common, but the condition can also be caused by chronic alcohol use, exposure to other toxins, and a large variety of other medical conditions--it is not unusual for the cause of the condition to go undiagnosed. Neuropathic pain is frequently chronic, and tends to have a less robust response to treatment with opioidsNociceptive pain Nociceptors are the nerves which sense and respond to parts of the body which suffer from damage. They signal tissue irritation, impending injury, or actual injury. When activated, they transmit pain signals (via the peripheral nerves as well as the spinal cord) to the brain. The pain is typically well localized, constant, and often with an aching or throbbing quality. Examples include sprains, bone fractures, burns, bumps, bruises, inflammation (from an infection or arthritic disorder), obstructions, and myofascial pain (which may indicate abnormal Visceral pain is the subtype of nociceptive pain that involves the internal organs. It tends to be episodic and poorly localized. Nociceptive pain is usually time limited, meaning when the tissue damage heals, the pain typically resolves. Neuropathic pain Neuropathic pain is the result of an injury or malfunction in the peripheral or central nervous system. The pain is often triggered by an injury, but this injury may or may not involve actual damage to the nervous system. Nerves can be infiltrated or compressed by tumors, strangulated by scar tissue, or inflamed by infection. The pain frequently has burning, lancinating, or electric shock qualities. Persistent allodynia, pain resulting from a nonpainful stimulus such as a light touch, is also a common characteristic of neuropathic pain. The pain may persist for months or years beyond the apparent healing of any damaged tissues. In this setting, pain signals no longer represent an alarm about ongoing or impending injury, instead the alarm system itself is malfunctioning. Examples include post herpetic neuralgia, reflex sympathetic dystrophy, components of cancer pain, phantom limb pain, carpal tunnel syndrome, and peripheral neuropathy. Among the many causes of peripheral neuropathy, diabetes is the most common, but the condition can also be caused by chronic alcohol use, exposure to other toxins, and a large variety of other medical conditions--it is not unusual for the cause of the condition to go undiagnosed. Neuropathic pain is frequently chronic, and tends to have a less robust response to treatment with opioids

94. Opioids for Chronic Non-Cancer Pain Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain: 2010 Update 94

95. What is New in this Revised Guideline  New data, including scientific evidence to support the 120mg MED dosing threshold Tools for calculating dosages of opioids during treatment and when tapering Validated screening tools for assessing substance abuse, mental health, and addiction 95

96. What is New in this Revised Guideline  Validated two-item scale for tracking function and pain Urine drug testing guidance and algorithm Information on access to mentoring and consultations (including reimbursement options) New patient education materials and resources Guidance on coordinating with emergency departments to reduce opioid abuse New clinical tools and resources to help streamline clinical care 96

97. Recommended Principles for prescribing chronic opioids Single prescriber Single pharmacy Patient and prescriber sign opioid agreement Lowest possible effective dose should be used Be cautious when using opioids with conditions that may potentiate opioid adverse effects (including COPD, CHF, sleep apnea, current or past alcohol or substance abuse, elderly, or history of renal or hepatic dysfunction). Do not combine opioids with sedative-hypnotics, benzodiazepines or barbiturates for chronic non-cancer pain unless there is a specific medical and/or psychiatric indication for the combination and increased monitoring is initiated 97

98. Recommended Principles for prescribing chronic opioids Routinely assess function and pain status Monitor for medication misuse Random urine drug testing to objectively assure compliance 98

99. Injection Therapy Cochrane Review Injection therapy for subacute and CLBP 18 RCTs (ESI, facet injections, trigger points) No statistical pooling secondary to heterogeneity of the trials Conclusion: �There is insufficient evidence to support the use of injection therapy in subacute and CLBP�. 99

100. Injection Therapy Injection therapy for subacute and CLBP- An Updated Cochrane Review. Staal JB, de Bie RA. Spine. Vol. 34, No.1, pp 49-59. 2009 ESI vs. Placebo Injections 2 trials evaluate short term effects One high quality and one low quality study No significant result for pain relief or other outcomes 100

101. Injection Therapy ESI vs. Other Treatments 3 studies ESI vs. NSAIDS ( low quality study) ESI vs. Intrathecal Midazolam (low quality study) ESI vs. morphine vs. ESI + morphine (high quality study) Limited evidence of no significant differences in short term pain relief 101

102. Injection Therapy Facet Injections vs. Placebo Injections 2 trials (1 high quality and 1 low quality) Moderate evidence that facet joint injections are not significantly different from placebo injections for short-term pain relief and improvement of disability Limited evidence that facet joint injections are not significantly different from placebo injections on work attendance. 102

103. Spinal Injection Procedures Spinal Injection Procedures: A Review of Concepts, Controversies, and Complications. Heran MK, Smith AD. Radiol Clin N. Am 46(2008) 487-514. Nerve root injections are of limited use in the evaluation of spinal disorders with radicular features. Their variability in their technique and the heterogeniety in causative etiologies does not allow for critical appraisal of the existing data. 103

104. Spinal Injection Procedures Long term efficacy of ESIs has not been shown with lack of a preferred method for administration of medications. The number and frequency of ESIs is arbitrary. Patients should not receive more than 3 injections in total. 104

105. Spinal Injection Procedures Intra-articular facet blocks and medial branch blocks are equivalent when assessing a patient for facet denervation procedures. However, the false positive rates for both procedures are too high for them to be useful. Rhizotomy procedures for facet-mediated pain do not provide sufficient long term relief to justify their use. The methods for evaluating which patients will benefit form these procedures are flawed, with no uniformity in how these procedures are performed. 105

106. Spinal Injection Procedures CT fluoroscopy adds nothing to percutaneous spinal injection procedures and only increases radiation exposure to the patient and the operator. Symptomatic synovial cysts are best managed surgically. 106

107. Spinal Injection Procedures Complications Spinal injection procedures can be associated with potentially devastating complications and should not be performed because there are limited data to support their efficacy as diagnostic and therapeutic procedures. 107

108. Spinal Injection Procedures Potential complications from facet denervation procedures Infection Bleeding Painful cutaneous dysesthesia Pain caused by neurogenic inflammation Pneumothorax Damage to spinal nerve or motor branches 108

109. Interventional Therapies, Surgery, and Interdisciplinary Rehabilitation for LBP Interventional Therapies, Surgery, and Interdisciplinary Rehabilitation for LBP: An Evidence Based Clinical Practice Guideline from the American Pain Society. SPINE. V. 34, No. 10, pp 1066-1077. 2009 Surgery for Low Back Pain: A Review for the Evidence for an American Pain Society Clinical Practice Guideline. Chou R, Baisden J, Carragee EJ. SPINE V. 34, No. 10, pp 1094-1109. 2009 109

110. Prolotherapy Condition: NS LBP Level of Evidence: Good: consistent results from well designed, well conducted studies; at least 2 higher quality trials. Net Benefit: No benefit Grade: Panel recommends against the intervention. 110

111. Intradiscal steroid injection Condition: Presumed discogenic pain Level of Evidence: Good: consistent results from well designed, well conducted studies; at least 2 higher quality trials. Net Benefit: No benefit Grade: Panel recommends against the intervention. 111

112. Facet injection Condition: Presumed facet pain Level of Evidence: Fair: at least 1 higher quality trial, >2 higher quality trials with some inconsistency, or >2 lower quality trials with consistent results, or multiple consistent cohort studies. Net Benefit: No benefit Grade: Panel recommends against the intervention. 112

113. Botulinum toxin injection Condition: NS LBP Level of Evidence: poor- large and unexplained inconsistency between higher quality trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 113

114. ESI Condition: NS LBP Level of Evidence: poor- large and unexplained inconsistency between higher quality trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 114

115.  Medial Branch Block (therapeutic)  Condition: Presumed Facet joint pain Level of Evidence: poor- large and unexplained inconsistency between higher quality trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 115

116. Radiofrequency denervation Condition: Presumed facet joint pain Level of Evidence: poor- large and unexplained inconsistency between higher quality trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 116

117. Radiofrequency denervation Condition: Presumed discogenic pain Level of Evidence: poor- large and unexplained inconsistency between higher quality trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 117

118. Percutaneous Intradiscal Radiofrequency thermocoagulation Condition: Presumed Facet joint pain Level of Evidence: poor- large and unexplained inconsistency between higher quality trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 118

119. Coblation Nucleoplasty Condition: Presumed discogenic pain Level of Evidence: NO trials Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 119

120. Spinal cord Stimulation Condition: NS LBP Level of Evidence: NO trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 120

121. Intrathecal therapy Condition: NS LBP Level of Evidence: NO trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 121

122. RF Denervation Condition: Radiculopathy Level of Evidence: poor- large and unexplained inconsistency between higher quality trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 122

123. Coblation Nucleoplasty Condition: Radiculopathy with prolapsed lumbar disc Level of Evidence: NO trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 123

124. Spinal cord Stimulation Condition: Radiculopathy with prolapsed lumbar disc Level of Evidence: NO trials; Net Benefit: Unable to estimate Grade: Evidence that the intervention is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. 124

125. ESI Condition: Radiculopathy with prolapsed lumbar disc Level of Evidence: Fair: at least 1 higher quality trial, >2 higher quality trials with some inconsistency, or >2 lower quality trials with consistent results, or multiple consistent cohort studies. Net Benefit: MODERATE for SHORT TERM only ( 3 months) Mean 10-20 point improvement of VAS pain scale Mean 10-20 point improvement of ODI scale, 2-5 points on RDQ, or equivalent Grade: Panel recommends the intervention. +at least fair evidence that intervention improves health outcomes, benefits moderately outweigh harms OR Benefits are small but there are no significant harms, costs or burden associated with the intervention. 125

126. SCS Condition: FBSS with persistent radiculopathy Level of Evidence: Fair: at least 1 higher quality trial, >2 higher quality trials with some inconsistency, or >2 lower quality trials with consistent results, or multiple consistent cohort studies. Net Benefit: MODERATE Mean 10-20 point improvement of VAS pain scale Mean 10-20 point improvement of ODI scale, 2-5 points on RDQ, or equivalent Grade: Panel recommends the intervention. +at least fair evidence that intervention improves health outcomes, benefits moderately outweigh harms OR Benefits are small but there are no significant harms, costs or burden associated with the intervention. 126

127. Intradiscal steroid injection Condition: Radiculopathy with prolapsed lumbar disc Level of Evidence: Fair: at least 1 higher quality trial, >2 higher quality trials with some inconsistency, or >2 lower quality trials with consistent results, or multiple consistent cohort studies. Net Benefit: NO effect vs. chemonucleolysis (NO TRIALS VS. PLACEBO) Grade: Benefits only slightly outweigh harms, or the balance of benefits and harms are too close to justify a general recommendations 127

128. Review article Injection therapy and denervation procedures for chronic low back pain: a systematic review Henschke N. Eur Spine J. (2010) 19: 1425-1449 128

129. Chemonucleolysis One RCT (chemonucleolysis vs. discectomy) n=68 subjects Limitations in design, inconsistency and imprecision Chemonucleolysis is no more effective than discectomy over long term follow up 129

130. Facet joint injections Facet joint injections (corticosteroids vs. placebo) 2 RCTs Low quality evidence that there is no significant difference in effect between facet joint injections with corticosteroids and placebo injections for short to intermediate term pain relief and improvement in function. 130

131. Facet joint injections 5 RCTs (RCTs corticosteroid vs. lidocaine; vs. home exercise; vs. sodium hyaluronate injections; vs. local anesthetics only; vs. sarapin) There is very low quality evidence that facet injections with corticosteroids are more effective than the comparison treatment. 131

132. ESI RCTs Corticosteroid vs intrathecal benzodiazepine Steroid with targeted epidural local anesthetic vs. steroid with spinal endoscope Epidural with ropvacaine vs. epidural with bupivacaine There is low quality evidence that there is no significant difference in the different methods studied Post treatment, no significant differences between the groups were reported for pain relief or general improvement 132

133. IM injections B12 1 RCT � B12 vs. placebo Low quality evidence that Vit. B12 injections are more effective than IM placebo injections for short term pain relief and improvement in function. 133

134. IM injections Botulinum Toxin A 1 RCT � Botox vs. placebo saline Low quality evidence that Botox A injections are more effective for pain relief in the short and intermediate term than placebo. 134

135. Percutaneous Intradiscal RF thermocoagulation 3 RCTs (Percutaneous Intradiscal RF thermocoagulation vs. placebo) Low quality evidence that there is no difference between Percutaneous Intradiscal RF thermocoagulation and placebo in pain and function status over intermediate or long term follow up. 135

136. Intradiscal electrothermal therapy (IDET) Intradiscal electrothermal therapy vs. Placebo 2 RCTs Low quality evidence that IDET is more effective than placebo for pain relief or functional improvement over long term (6 months). 136

137. RF denervation of facet joints RF denervation of facet joints vs. placebo 5 RCTs Low quality evidence that RF denervation is more effective than placebo for pain relief (short term and long term) or functional improvement over short term. 137

138. The End.. Thank you for your time! 138