Chronic Pain and Opioids

Educational Objectives

The goal of this program is to improve management of opioid use for chronic pain in the outpatient setting. After hearing and assimilating this program, the clinician will be better able to:

1. Identify the common adverse effects and long-term risks associated with opioid use.
2. Implement current guidelines and recommendations for opioid use in patients with chronic pain.
3. Develop strategies for tapering of opioids in short- and long-term opioid users.

Summary

Evidence: the SPACE trial by Krebs et al (2018) showed no significant difference in pain-related function or intensity at 12 mo for opioids compared with non-opioid medications; pain intensity was significantly lower in the non-opioid group; opioid group experienced more adverse effects; the 2022 Centers for Disease Control and Prevention (CDC) guidelines suggest that non-pharmacologic treatments and non-opioid medications are as effective as opioids; opioids may offer short term (<6 mo) improvements in pain and function compared with placebo; long-term use (>3 mo) is associated with increased harm and reduced effectiveness

Risks associated with chronic opioid use: include respiratory depression, nausea, vomiting, itching, drowsiness, impaired driving ability, immune system suppression, constipation, hyperalgesia, weight gain, mood changes, seizures, low testosterone, tremors, decreased bone density, tolerance, addiction, and substance use disorders (SUDs)

Evidence: Hurtado et al (2024) showed a dose dependent increase in the risk for death in chronic opioid users (non-cancer pain) in the United States, United Kingdom, and Canada; the hazard ratio was 1.86 for 50 to 120 morphine mg equivalents (MME) per day, 6.0 for 120 to 200 MME, and >11 for >200 MME; the overall risk for death in opioid users was increased by 25%; concurrent depression, substance use, antipsychotic use, and gabapentinoid use increased the risk for mortality; low doses (50-100 MME) are associated with increased overdose risk compared with very low doses (<20 MME); in a national sample of patients from the Veterans Affairs, mean prescribed daily opioids was 98 MME for patients with fatal overdose and 48 MME for those with nonfatal overdose; Vowles et al (2015) suggested a misuse rate of 21% to 29% and an opioid use disorder (OUD) rate of 8% to 12% among chronic opioid users; Wilton et al (2021) found that 3% to 4% of patients on chronic opioid treatment for non-cancer pain initiated intravenous drug use; this rate is 8-fold higher compared with patients not on opioids; Howell et al (2021) found that only 2% of patients in a high risk monitoring program based on physician preference were identified as having OUD using the International Classification of Diseases 10 criteria; manual review using Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria revealed that 73% of the monitored group and 14% of the matched control group had moderate to severe OUD

History: opioids were introduced in the United States in the 1800s for various uses; morphine was developed for war injuries and heroin was (mistakenly) introduced as a less addictive option; regulations in the early 1900s included the Pure Food and Drug Act (1906) and the Harrison Narcotic Act (1914); the Federal Bureau of Narcotics was formed in 1930; the Controlled Substance Act (1970) categorized drugs based on addiction potential, and the Narcotic Treatment Act (1974) required registration to dispense medications for OUD and recognized methadone as a maintenance treatment for OUD

Opioid crisis: 1999 to 2010 (wave 1) — prescription opioid sales and deaths quadrupled; 2010 to 2016 (wave 2) — heroin use increased, and heroin-related deaths surpassed prescription opioid deaths in 2015; 2016 to present (wave 3) — fentanyl related deaths doubled from 2015 to 2020; in 2022, ≈15,000 overdose deaths (14%) were associated with prescription opioids; the 2016 CDC guidelines led to opioid tapering and deprescribing

Opioid misuse: national data show that 8.2 million individuals misused opioids in 2023; 93% of opioid misuse involved prescription pain relievers; 47% of misused prescription opioids were obtained from a health care provider; 40% of individuals obtained opioids through friends or relatives

Opioid use disorder: affected 17% of adults in the United States in 2023; pain reliever use disorder is the third most common SUD (after alcohol and cannabis), affecting 5.3 million individuals; a 2021 survey revealed a significant increase in diagnosed OUD; criteria for diagnosis — includes unsuccessful attempts to control use, opioid craving, and significant time spent obtaining, using, or concealing opioid use; ≥33% of those with OUD meet criteria for moderate to severe disorder; Larochelle et al (2016) found that a significant percentage of patients who had a prior overdose experienced a repeat overdose; 2 yr after the initial overdose, the cumulative incidence of a repeat overdose was 17% for patients prescribed >100 MME per day, 15% for 50 to 100 MME/day, and 9% for <50 MME/day; all patients on chronic opioids must be assessed for OUD

CDC guidelines: initiation and continuation — both 2016 and 2022 versions prioritize non-pharmacologic and non-opioid treatments, multimodal approaches, establishing treatment goals, and discussing risks vs benefits; the 2022 update emphasizes that opioids should not be first-line treatment for subacute or chronic pain

Selection and dosage: both recommend immediate release opioids at the lowest effective dose, with reassessment upon dose increases; the 2016 guideline stated that >50 MME is associated with higher risk for overdose and to avoid ≥90 MME, leading to unintended rapid tapers; the 2022 version advises against increasing doses likely to yield diminishing returns (>50 MME) and suggests starting doses of 5 to 10 MME, with a total daily dose of 20 to 30 MME

Duration, follow-up, and discontinuation: the 2016 guideline recommended limiting acute pain prescriptions to ≤3 days and stated that prescriptions for >7 days are rarely needed; this led to insurance restrictions; the 2022 update recommended evaluations every 2 wk initially, then at 1 mo; updated guidelines advised against abrupt discontinuation or rapid dose reduction (unless life threatening, impending overdose, eg, confusion, sedation, slurred speech, is present), and recommended slow tapers (≤10% per mo) for long term users

Risk and harm mitigation: both guideline versions emphasize discussing risk factors, using risk mitigation strategies (eg, naloxone for patients with SUD history, high doses, or concurrent benzodiazepine use), reviewing prescription drug monitoring program (PDMP) data, urine drug screening, avoiding concurrent opioid and benzodiazepine prescriptions, and offering OUD treatment if needed

Urine toxicology tests: primarily confirm the presence of a substance in the body ≤3 days; they do not diagnose SUD (which requires DSM-5 criteria)

Urine drug tests: screens (immunoassays) — are fast but limited; tests for fentanyl, methadone, oxycodone, and buprenorphine are often lacking; they may produce false positives, particularly for amphetamines (requiring reflex testing to differentiate amphetamines from methamphetamines); a positive result on a screen for cocaine is considered accurate; comprehensive tests (liquid chromatography-mass spectrometry) — are expensive and slower (turnaround of 1-15 days), but highly accurate with no false positives

Treatment plans: it is important to apply consistent treatment plans for chronic opioid management to avoid documented disparities, particularly with respect to dosage, safeguards, and access to care for Black patients

Initiation: avoid opioids for chronic non-cancer pain; for acute pain, consider risks vs benefits and pain severity, prescribe for the shortest duration possible, and schedule follow-up visits every 2 to 4 wk; discuss goals and expectations upfront, including regular visits, urine toxicology tests, and restrictions on outside prescriptions; urine toxicology testing should be performed before starting opioids and at least annually thereafter; check the PDMP with each refill, and use the lowest effective dose and short-acting opioids when possible

Continuation: when continuing opioids for patients already taking them, regularly assess risks vs benefits, functional improvement, and goals; use of a pain agreement is recommended to clarify expectations for both patient and provider; urine drug screens should be done at least annually, or every 6 mo for those on daily opioids; regular visits and PDMP checks are necessary; prescribe naloxone for patients on >50 MME or those co-prescribed benzodiazepines; controlled substance review committees are available in some institutions to review complex cases

Tapering: a thorough assessment of the risks vs benefits of continuing the current opioid dose is necessary; if benefits outweigh risks, continued monitoring (at least quarterly) and documentation are essential; if risks begin to outweigh benefits, a slow taper should be discussed and initiated with the patient; the goal is not necessarily immediate cessation or tapering to zero; the focus is finding a dose at which the benefit-risk balance is optimized; if a patient is unable to taper to a dose where benefits outweigh risks, consider the possibility of OUD, opioid misuse, or other problematic opioid relationships; in these cases, transitioning to buprenorphine may be appropriate

Indications: include patient request, pain improvement or resolution, lack of functional improvement, prolonged treatment with unclear benefit-risk ratio, lack of clear benefit from higher dosages, side effects affecting quality of life, evidence of misuse or overdose, warning signs of impending events (eg, confusion, sedation, or slurred speech), concerns about other medications (eg, benzodiazepines), and concurrent medical issues (eg, sleep apnea, liver or kidney problems, fall risk)

Rate of taper: once the decision to taper is made, the rate of taper depends on the duration of opioid use; for long-term use (>1 yr), a taper of ≤10% per mo is recommended; for short-term use (weeks or months), a reduction of 10% per wk of the starting dose is appropriate until reaching 30% of the original dose, at which point the reduction should be 10% of the remaining dose to minimize withdrawal symptoms; rapid tapers are indicated for safety reasons, eg, recent overdose or impending overdose, and may involve switching to buprenorphine; life stressors may necessitate pausing the taper process, but dose increases should be avoided; multimodal pain management should be implemented, and clear documentation and planning for next steps are essential; successful tapering should lead to improvements in quality of life, including mood, cognition, social functioning, and a reduction in overdose risk and adverse effects

Evidence: Agnoli et al (2021) evaluated patients on >50 MME for >12 mo, and showed that a dose reduction of 39% ≤60 days increased the risk for overdose or withdrawal and mental health crisis by ≈50%; this study did not assess OUD or clarify whether tapers were initiated by the patient or clinician; Glanz et al (2023) found that reductions of >30% per mo were associated with overdose; DiPrete et al (2022) found that rapid dose reductions (>10% per wk) in patients on >90 MME of opioids increased the risk for fatal or nonfatal overdose (HR 1.43); very rapid reductions doubled or tripled the risk; the study also found increased rates of OUD after rapid tapers; chronic pain and OUD often co-occur, and untreated OUD increases mortality; legal regulations mandate treatment with medications for OUD

Buprenorphine: may be considered off-label for patients with problematic opioid use, even without known OUD diagnosis; certain formulations (eg, Butrans patch, Belbuca buccal film) are approved by the US Food and Drug Administration for pain management; buprenorphine has shown effectiveness in various pain types, including cancer and neuropathic pain, with fewer adverse effects; the dose range for the buccal film is 3 to 36 MME, and that of the patch ranges from 30 to 40 MME

Readings

Agnoli A, Xing G, Tancredi DJ, et al. Association of dose tapering with overdose or mental health crisis among patients prescribed long-term opioids [published correction appears in JAMA. 2022 Feb 15;327(7):688. doi: 10.1001/jama.2021.22379.] [published correction appears in JAMA. 2022 Feb 15;327(7):687. doi: 10.1001/jama.2022.0231.]. JAMA. 2021;326(5):411-419. doi:10.1001/jama.2021.11013; DiPrete BL, Ranapurwala SI, Maierhofer CN, et al. Association of opioid dose reduction with opioid overdose and opioid use disorder among patients receiving high-dose, long-term opioid therapy in North Carolina. JAMA Netw Open. 2022;5(4):e229191. Published 2022 Apr 1. doi:10.1001/jamanetworkopen.2022.9191; Gangal A, Stoff B, Blalock T. The 2022 CDC opioid prescription guideline update: relevant recommendations and future considerations. JAAD Int. 2023;13:48-49. Published 2023 Jul 21. doi:10.1016/j.jdin.2023.07.006; Glanz JM, Xu S, Narwaney KJ, et al. Association between opioid dose reduction rates and overdose among patients prescribed long-term opioid therapy. Subst Abus. 2023;44(3):209-219. doi:10.1177/08897077231186216; Howell BA, Abel EA, Park D, et al. Validity of Incident Opioid Use Disorder (OUD) diagnoses in administrative data: a chart verification study. J Gen Intern Med. 2021;36(5):1264-1270. doi:10.1007/s11606-020-06339-3; Hurtado I, Robles C, García-Sempere A, et al. Long-term use of prescription opioids for non-cancer pain and mortality: a population-based, propensity-weighted cohort study. Public Health. 2024;232:4-13. doi:10.1016/j.puhe.2024.04.009; Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the space randomized clinical trial. JAMA. 2018;319(9):872-882. doi:10.1001/jama.2018.0899; Larochelle MR, Liebschutz JM, Zhang F, et al. Opioid prescribing after nonfatal overdose and association with repeated overdose: a cohort study. Ann Intern Med. 2016;164(1):1-9. doi:10.7326/M15-0038; Vowles KE, McEntee ML, Julnes PS, et al. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain. 2015;156(4):569-576. doi:10.1097/01.j.pain.0000460357.01998.f1; Wilton J, Abdia Y, Chong M, et al. Prescription opioid treatment for non-cancer pain and initiation of injection drug use: large retrospective cohort study. BMJ. 2021;375:e066965. Published 2021 Nov 18. doi:10.1136/bmj-2021-066965.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Ristau's lecture includes information about the off-label use of buprenorphine for problematic opioid use or opioid use disorder.

Acknowledgements

Dr. Ristau was recorded exclusively for Audio Digest on January 30, 2025. Audio Digest thanks the speakers and the presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.50 CE contact hours.

Lecture ID:

FP731701

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.