Managing Pain in Patients on Pharmacotherapy for Opioid Use Disorder

Transcription

1 Managing Pain in Patients on Pharmacotherapy for Opioid Use Disorder Roger Chou, MD, FACP Professor, Department of Medical Informatics and Clinical Epidemiology; Medicine Director, Pacific Northwest Evidence-based Practice Center *Images used for educational purposes only. All copyrights belong to image owners*

2 Objectives Describe basics of opioid pharmacology Use buprenorphine for management of opioid use disorder Describe relationship between addiction and pain Use principles for management of acute and chronic pain for patients on medication for opioid use disorder

3 Case 53-year-old male with history of opioid use disorder, maintained on buprenorphine/naloxone Depression, fatigue Unemployed Presents to ER with severe low back pain with sciatica, thought related to herniated disc

4 Case (Continued) Has been taking buprenorphine/naloxone 8/2 mg once daily for opioid use disorder related to prescription opioids, with no issues On NSAIDs for chronic knee pain Pain 6/10 on average, with day to day fluctuation

5 Case Questions to Consider: What options are available for management of acute pain? How does buprenorphine impact management of acute pain? How should this patient s acute pain be managed?

6 Chronic Pain and Opioids (1) Chronic pain highly prevalent, with substantial burdens Chronic pain: lasting >3 months Reported by 1/3 of adults Opioids commonly prescribed for chronic pain 5% of US adults on long-term opioids The US, ~5% of world s population, use 80% of world s opioids: (99% of global hydrocodone consumption) a Boudreau et al Pharmacoepidemiol Drug Saf 2009; International Narcotics Control Board Report United Nations Pubns p. 20; Caudill-Slosberg MA. Pain 2004;109:514; Sullivan MD 2008;138:440; Campbell CI Am J Pub Health 2010;100:2541

7 Chronic Pain and Opioids (2) Prescribed at higher doses, more Schedule II Knowledge Check answer: False, patterns in the U.S. differ substantially from the rest of the world Opioids: potential harm to patients and to society a Boudreau et al Pharmacoepidemiol Drug Saf 2009; International Narcotics Control Board Report United Nations Pubns p. 20; Caudill-Slosberg MA. Pain 2004;109:514; Sullivan MD 2008;138:440; Campbell CI Am J Pub Health 2010;100:2541

8 Rates of prescription painkiller sales, deaths and substance abuse treatment admissions ( ) US opioid sales quadrupled Since 2008, 15,000 deaths per year. This exceeds MVA deaths in 30 states. Slide courtesy Mark Sullivan

9 Nonmedical pain medication use among adolescents and young adults SAMSHA 2014 National Survey on Drug Use and Health

10 Risk of prescription opioid overdose Rates are per 100,000 population age-adjusted to 2008 U.S. standard population

11 How Did We Get Here? (1) Perceived under treatment of chronic pain Pain as the 5 th vital sign Opioid Marketing Regulations >20 states around opioids for chronic pain Low-risk misuse in palliative care settings - patients rarely demonstrate euphoric responses to opioid drugs, and neither analgesic tolerance nor physical dependence is a significant clinical problem. Portenoy RK. J Law Medicine Ethics 1996;24:296 Studies: benefits of long-term opioid therapy for chronic pain Limited information on patients, mostly low doses

12 How Did We Get Here? (2) No ceiling dose in palliative care settings Escalation of the opioid dose until either adequate analgesia occurs or intolerable and unmanageable side effects supervene is standard practice in cancer pain management. - Portenoy RK. J Pain Symptom Management 1996;11:203 Emphasis on round-the-clock dosing, sustainedrelease formulations Portenoy RK 1986;25:171; Haythornthwaite JA 1998;15:185

13 Opioid Use Disorder (1) DSM-5: A problematic pattern of opioid use leading to clinically significant impairment or distress 2015: 2 million Americans with OUD due to prescription drugs, ~600,000 due to heroin OUD: decreased quality of life, mortality morbidity and

14 Opioid Use Disorder (2) Treatment: FDA-approved medications: agonists, partial agonists, antagonists Block euphoric, sedating effect, craving, mitigate withdrawal Decrease illicit use and misuse medication, improves social functioning Criminal activity, infection, disease

15 Rates of death associated with heroin and prescription opioids Dart RC et al. N Engl J Med 2015;372:

16 First opioid of abuse in heroin users Knowledge check answer: C Cicero TJ et al. JAMA Psychiatry 2014

17 Opioid Pharmacology (1) Opioid mu-receptors mediate analgesic effects and AE s Agonists (opioid), partial agonists (opioid effects, and blocks others), antagonists (blocker) Natural, semi-synthetic, synthetic Half-life: 2-4 hours and up to hours Pathan H. Br J Pain 2012;6:11-16

18 Opioid Pharmacology (2) Ongoing exposure: tolerance and physical dependence Tolerance > dose same effects (analgesic and AE s) Individual variability tolerance Physical dependence: withdrawal when stopped Tolerance and physical dependence:? addiction (behavior defines) Pathan H. Br J Pain 2012;6:11-16

19 Opioid Pharmacology (3) There appears to be no limit to the development of tolerance, and with appropriate dose adjustments, patients can continue to obtain pain relief. -Inturrisi C. Clin J Pain 2002;18:S3-13 No theoretical dose ceiling Pathan H. Br J Pain 2012;6:11-16

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21 Opioid Classes with Examples Full mu agonists Morphine, Oxycodone, Hydrocodone, Hydromorphone, Fentanyl, Methadone, Oxymorphone Opioids Partial mu agonist Buprenorphine Mixed agonist/ antagonists Dual mechanism Pentazocine Tramadol, Tapentadol

22 Buprenorphine (1) Partial mu-opioid agonist Opioid agonist effects at lower doses, plateau at higher doses Agonist effects: analgesic and other effects of opioid mu-receptors At higher doses can act like antagonists Lutfy K. Curr Neuropharmacol 2004;2:

23 Buprenorphine (2) High affinity mu-opioid receptor Can displace full agonist and precipitate opioid withdrawal Less euphoric SL formulation: treatment of opioid use disorder provides 4-6 hours of analgesia Lutfy K. Curr Neuropharmacol 2004;2:

24 Buprenorphine (3) Several formulations For OUD SL tablet, buccal film strip with naloxone except mono tablet Naloxone: opioid antagonist is inert when taken as prescribed; prevent crushing/manipulation Implant 6 month: stabilize patients 8 mg or < Chronic pain: transdermal patch Lutfy K. Curr Neuropharmacol 2004;2:

25 Buprenorphine for Opioid Use Disorder Reduces opioid use: in long-term treatment, increases retention - Suppresses cravings, prevents withdrawal - As effective as methadone Can be prescribed in office setting - Drug Abuse Treatment Act of 2000 (DATA 2000) - Requires training and a waiver - Free resources PCSS-MAT (pcssmat.org)

26 Dahan A. Br J Anaesth 2005;94: Dose-response relationship for respiratory depression Knowledge check answer: B

27 Methadone (1) Methadone deaths, disproportionate to prescribing Methadone: 1.7% of opioid rx s in 2009 and 9.0% of morphine equivalents in 2010 a Involved: 31% of opioid-related deaths, 40% single-drug deaths MMWR 2012;61:493-7; Chou R. J Pain 2014;15:321-37

28 Methadone (2) Half-life: 15 to 60 hours, up to 120 hours 60-hour half-life = 12 days steady-state Start at 2.5 mg q8 hrs, increase slowly Higher doses: risk cardiac arrhythmia, potentially fatal Converting from other opioids to methadone is complicated Morphine/methadone dose conversion ratio higher doses

29 Time to Reach Steady State CONCENTRATION Steady State Attained after approximately four half-times Time to steady state independent of dosage Steady State Concentrations TIME (multiples of elimination half-time)

30 Prolonged QTc and torsades de pointes Stringer J. Am J Health Syst Pharm 2009;66:825-33

31 Naltrexone Opioid antagonist Monthly IM injection: shown to prevent relapse Blocks euphoric effects May be useful: chronic relapse, cooccurring alcohol use disorder

32 Epidemiology of Pain and Opioid Use Disorder Pain is common in persons with OUD About 50% of treatment-seeking veterans with opioid use disorder report moderate to severe pain One-third to two-thirds of patients on methadone for opioid use disorder have chronic pain Pain has an important role in initiating and continuing/reinforcing opioid use Trafton 2000;Jamison 2000;rosenblum 2003; Karasz 2004; Sharpe Potter J 2010

33 Pain Treatment in Opioid Use Disorder Principles Safe and effective pain treatment Support ongoing treatment: opioid use disorder - Recovery activities - Reward exposure - Support medication management Address pain facilitators Alford DP. Ann Intern Med 2006;144:127-34

34 Listen To and Engage with Patient Past experiences can shape treatment choices Perceptions and expectations of treatment efficacy impacts outcomes Plan treatment Patients: fear undertreatment, label, withdrawal Engagement: self-management, treatment planning - Focus on nonmedication modalities Merrill JO. J Gen Intern Med 2002; Whitten CE. Permanente Journal 2005;9:41-8

35 Treat Pain Safely and Effectively Untreated pain: risk self-medication and misuse Provide appropriate pain relief - Nonmedication - Less rewarding medications - Limit opioids to appropriate amount, length Plan for anticipated procedures Alford DP. Ann Intern Med 2006;144:127-34

36 Address Pain Facilitators Commonly: Acute pain Anxiety, PTSD, sleep disturbance, substance issues, withdrawal Chronic, noncancer pain Anxiety, PTSD, depression, functional losses Terminal pain Anxiety, spiritual challenges, grief Alford DP. Ann Intern Med 2006;144:127-34

37 Address Opioid Use Disorder (1) Acknowledge the challenge Assurance of treatment Encourage and support recovery: Discuss what has been valuable for patient Psychosocial support Counselor, self-help, faith-based, mindfulness, etc. Schuckit MA. N Engl J Med 2016;375:

38 Schuckit MA. N Engl J Med 2016;375: Address Opioid Use Disorder (2) Encourage and support recovery - Continued: Pharmacologic supports: methadone, buprenorphine Increase safety: limited supply Discuss and plan relapse prevention strategies (including overdose safety and use of naloxone) Address physiologic issues of drug use Treat withdrawal as appropriate Anticipate opioid tolerance in opioid-dependent individuals Be aware of opioid reward effects

39 Address Opioid Use Disorder Consider Opioid Reward Some drugs and dosing regimens induce greater reward than others Greater blood levels Specific receptor effects More intermittent dosing (Kreek et al, 1998; Gardner, 2011) Long-acting, controlled release: less rewarding IV or bolus dosing Does not occur in all individuals, clinical benefits of using less rewarding opioid/regimens not proven Schuckit MA. N Engl J Med 2016;375:

40 Address Opioid Use Disorder Consider Opioid Reward Effects Alford DP. Ann Intern Med 2006;144: Strategies to minimize reward effects, if desired Slow onset drugs: methadone Sustained-release meds: oxycodone, morphine, fentanyl Kappa agonists (pentazocine, butorphanol) - Note mu antagonism, can t use mu agonists Partial mu agonists (buprenorphine or tramadol) Acute pain, focus on relief. Transient reward unlikely to affect long-term effect Knowledge check answer: False

41 Acute Pain in Persons on Agonist Treatment (1) Limited evidence optimal management Often require opioids Daily equivalence of agonist treatment before analgesic effects Increased pain sensitivity and opioid crosstolerance Multimodal approaches High abuse potential: buccal/intranasal fentanyl Sporer KA. Ann Emerg Med. 2004;43:

42 Acute Pain in Persons on Agonist Treatment (2) Immediate-release opioids preferred: dose adjustments, concern reward acute setting Duration, time-limited prescription Management issues vary: agonist medication Sporer KA. Ann Emerg Med. 2004;43:

43 Buprenorphine for Opioid Use Disorder and Acute Pain Ceiling effects: respiratory depression Analgesic ceiling uncertain - Doubling dose increased analgesic effect by 3.5x, respiratory depression unchanged (Dahan A. Br J Anaesth 2006) Theoretically, may antagonize administered opioids, or block effects of opioids - Some experimental models show additive or synergistic effects (Engelberger W. Eur J Pharm 2006) Lack of evidence for optimal prescribing strategies Alford DP. Ann Intern Med 2006;144:127-34

44 Buprenorphine and Acute Pain Pharmacological treatment options (1) Nonopioid therapies: Acetaminophen NSAIDs Gabapentin/pregabalin Knowledge check answer: E Alford DP. Ann Intern Med 2006;144:127-34

45 Alford DP. Ann Intern Med 2006;144: Buprenorphine and Acute Pain Pharmacological treatment options (2) Opioid therapy Continue buprenorphine, titrate short-acting* Stop buprenorphine, use short-acting, then re-induce* Divide buprenorphine Q 6-8 hours Use supplemental doses or doses of buprenorphine Switch to methadone or other long-acting, titrate short-acting *Monitor: determine if buprenorphine blocking opioid effect

46 Methadone and Acute Pain (1) Methadone maintenance once daily Methadone for analgesia Q 6-8 hours Relapse risk increased in persons with inadequate pain control (Alford DP. Ann Intern Med 2006) Limited evidence opioid analgesics for acute pain post-operatively doesn t increase risk of relapse (Kantor TG. Drug and Al Dependence, 1980) Alford DP. Ann Intern Med 2006;144:127-34

47 Methadone and Acute Pain (2) Recommendations Continue verified methadone dose, consider Q 6-8 hours Use nonopioid analgesics Opioid may require higher doses, shorter interval dosing Avoid mixed agonist/antagonists can precipitate withdrawal Alford DP. Ann Intern Med 2006;144:127-34

48 Alford DP. Ann Intern Med 2006;144: Naltrexone and Acute Pain (1) Naltrexone blocks analgesic effects of opioids at standard doses Analgesia may be achieved doses 6 to 20 times higher, without respiratory depression (Dean RL. Pharmacol Biochem Behav 2006) Urgent acute pain Discontinue naltrexone Consult pain service: monitored, high-dose opioids Multimodal approach: nonopioids, regional anesthetic Use supplemental doses of buprenorphine

49 Naltrexone and Acute Pain (2) Perioperative pain management (Vickers AP BMJ 2006) Oral naltrexone: Discontinue 72-hours preoperatively (blockade effect reduced by 50% after 72 hours) Depot naltrexone: Discontinue for a month prior if possible (decline begins after 14 days) Alford DP. Ann Intern Med 2006;144:127-34

50 Chronic Pain in Persons on Agonist Treatment (1) Limited evidence on optimal management Pain and addiction often co-exist Opioids do not address psychosocial contributors Multimodal approaches Adjunctive medications for pain Address psychological issues Exercise, psychological, and other active modalities Alford DP. Ann Intern Med 2006;144:127-34

51 Chronic Pain in Persons on Agonist Treatment (2) Do not initiate opioids in untreated OUD Caution psychiatric comorbidities and drug misuse behaviors If opioids prescribed, use of less rewarding opioids Methadone and buprenorphine address both RCT: methadone and buprenorphine equivalent for pain in patients with addiction (Neumann A. J Addictive Dis 2013;32:68) Alford DP. Ann Intern Med 2006;144:127-34

52 Nonopioid Treatments for Pain (1) Nonopioid meds Analgesics: Acetaminophen, NSAIDs Antidepressants: SNRI s, TCA s Gabapentin/pregabalin Topical lidocaine, capsaicin

53 Nonopioid Treatments for Pain (2) Integrate psychotherapeutic cointerventions Chronic pain complex biopsychosocial issue Opioids do not address psychosocial contributors to pain; multimodal approach most effective Assess and treat for psychological comorbidities

54 Nonopioid Treatments for Pain (3) Integrate psychotherapeutic cointerventions (continued): Exercise therapy, CBT, functional restoration, therapy Motivational interviewing, relaxation techniques Address sleep issues Avoid benzodiazepines

55 Buprenorphine and Chronic Pain Buprenorphine effective treating chronic pain Transdermal and buccal formulations approved for chronic pain Evidence buprenorphine/naloxone patients with chronic pain and opioid use disorder reduces pain, opioid withdrawal, and abuse liability of oxycodone (Roux P. Pain 2013) Alford DP. Ann Intern Med 2006;144:127-34

56 Methadone and Chronic Pain (1) Methadone blocks euphoric effects of opioids, still experience analgesic effects Analgesia 6-8 hours after dose may indicate pain response Methadone closely monitored in treatment settings Methadone maintenance programs dose daily, some split dosing Alford DP. Ann Intern Med 2006;144:127-34

57 Methadone and Chronic Pain (2) Ideally, treat both opioid use disorder and chronic pain with methadone dosed every 6-8 hours in methadone treatment facility or primary care In practice, likely dosed daily, pain managed with other opioid in primary care Alford DP. Ann Intern Med 2006;144:127-34

58 Mitigating Risks Associated with Higher Doses of Opioids (1) Urine drug testing Prescription drug monitoring program (PDMP) Avoid sedative-hypnotics Frequent follow-up Addiction, pain, or psychiatric consultation Frequent refills with smaller quantities Dowell D. MMWR Rec Reports 2016;65:1-49

59 Mitigating Risks Associated with Higher Doses of Opioids (2) If opioids for acute pain: small quantities and duration-limited Avoid high doses Assess and treat psychiatric comorbidities Incorporate nonopioid therapies Abuse-deterrent formulations Naloxone co-prescription Dowell D. MMWR Rec Reports 2016;65:1-49

60 Prescription Drug Monitoring Programs Available now in most states Use of PDMPs identifies diversion and doctor shopping - Study found decreased inappropriate prescribing with centralized prescribing system - Canada a - Effects outcomes not known Use variable PDMPs vary in who can access, information sometimes available across states a Dormuth et al. CMAJ 2012

61 Urine Drug Testing (1) Identifies undisclosed risks Optimal frequency and usefulness of individualized vs. routine testing uncertain;?random testing Standridge JB 2010;81:635-40

62 Urine Drug Testing (2) Urine tests can be difficult to interpret - Need to understand metabolic pathways - Differential diagnosis results: poorly controlled pain, abuse, diversion - Potential for false reassurance - No evidence that urine drug testing improves patient outcomes; potential for harm - Cost-effectiveness a concern Standridge JB 2010;81:635-40

63 Dose and Risk of Overdose Studies show association between opioid dose and risk of overdose or death in patients with chronic pain Risk increase at low doses and continues to increase Studies attempted to control for other factors that could increase risk of overdose, but can t eliminate them Dowell D. MMWR Rec Reports 2016;65:1-49

64 Risk Ratio Courtesy Gary Franklin Dunn et al. Ann Intern Med 2010;152:85-92; Bohnert et al. JAMA 2011;305: ; Gomes et al. Arch Intern Med 2011;171: Dose-related risk of opioid overdose 10 9 Risk of adverse event Dunn 2010 Bhnert 2011 Gomes 2011 Sedler 2014 <20 mg/day mg/day mg/day >=100 mg/day Dose in mg MED

65 Tamper-Resistant Formulations Designed: tamper-resistant or co-formulated with antagonist or medications that produce noxious effects with tampering Effectiveness yet to be established Effective in patients who crush or inject opioids One study found patients on tamper-resistant formulation of long-acting opioids frequently switched to an alternative opioid or heroin a Knowledge check answer: False a Cicero et al. NEJM 2012

66 Naloxone Opioid antagonist: counteract respiratory effects Multiple routes of administration: IV, IM, SC, intranasal, endotracheal, nebulized/inhalation, buccal or sublingual FDA approved naloxone IM or SC auto-injector in 2014, intranasal formulation in 2015 Decreases risk overdose with in communitybased programs May precipitate withdrawal symptoms Boyer EW. N Engl J Med 2012;367:146-55

67 Case Patient in severe acute pain; adherent with buprenorphine with no issues Buprenorphine continued and placed on hydromorphone IR 2 mg q 4 hrs prn, titrated for pain relief; no withdrawal Pain still 7/10 after 3 weeks; started on gabapentin Referred for MRI which confirmed presence of herniated disc with nerve root impingement; referred for discectomy

68 Case (Continued) Weaned off buprenorphine prior to discectomy; morphine titrated for pain relief Received preoperative celecoxib and pregabalin Titrated off morphine 1 week after surgery Re-started and maintained on buprenorphine

69 PCSS-O and Treatment Resources (1) Providers Clinical Support-System for Opioid Therapies and Treatment : Collaborative effort led by American Academy of Addiction Psychiatry, funded by SAMHSA Free training and educational materials More detailed webinars on managing pain in patients with OUD available from the following PCSS-O webinars (some slides in this presentation adapted from these webinars)

70 PCSS-O and Treatment Resources (2) Free training and educational materials (cont.): Pade P, Savage SR, Weimer W. Opioids for pain treatment in persons with opioid use disorder. Weimer M. Managing pain in the patient with opioid use disorder before it manages you: inpatient management cases

71 PCSS-O and Treatment Resources (3) PCSS-O mentors comprise a national network of trained providers with expertise in addiction medicine/psychiatry and pain management. The mentoring program is available at no cost to providers Listserv: A resource that provides an Expert of the Month who will answer questions about educational content that has been presented through PCSS-O project. To join pcss-o@aaap.org.

72 Additional Educational and Training Resources NIH Pain Consortium Centers of Excellence in Pain Education modules: SAMHSA Training Materials and Resources for treatment of opioid use disorder: ASAM, AANP, AAPA buprenorphine waiver training for nurse practitioners and physician assistants:

73 Conclusions (1) Pain is common in opioid use disorder Address both Integrate nonopioid therapies Management of acute and chronic pain OUD requires understanding of pharmacology of the drugs used May require change in dosing, additional opioids Potential for opioid blockade or withdrawal in patients on buprenorphine

74 Conclusions (2) (understanding of pharmacology continued): Multimodal approaches Opioid analgesics acute pain: time and durationlimited Consider reward potential of opioids Risk mitigation strategies PDMP, UDT, frequent follow-up, naloxone Avoid concomitant benzodiazepines

75 References Alford DP, Compton P, Samet JH. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Ann Intern Med 2006;144: Chou R, Turner JA, Devine EB, Hansen RN, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways To Prevention workshop. Ann Intern Med. 2015;162: Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain United States, 2016 Quick guide for physicians. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration. Available at:

76 Unit Resources (1): Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health (pdf) National Institute on Drug Abuse - Overdose Death Rates Boston University - Scope of Pain SAMHSA - Medication-Assisted Treatment: Buprenorphine treatment/treatment/buprenorphine SAMHSA - Clinical Use of Extended Release Injectable Naltrexone in the Treatment of Opioid Use Disorder - A Brief Guide

77 Unit Resources (2): Acute Pain Management for Patients Receiving Maintenance Methadone or Buprenorphine Therapy (Alford et. al, 2006) Centers for Disease Control and Prevention - Nonopioid Treatments for Chronic Pain (pdf) Providers Clinical Support System For Opioid Therapies (PCSS-O) PCSS-O Webinar: Opioids for Pain Treatment in Persons with Opioid Use Disorder PCSS-O Webinar: Managing Pain in the Patient with Opioid Use Disorder: Inpatient Management