The Opioid Crisis: Safe Prescribing For Patients With Acute And Chronic Pain

Educational Objectives

The goal of this program is to improve the safety of patients being treated for pain. After hearing and assimilating this program, the clinician will be better able to:

1. Write institutional guidelines for treatment of acute and chronic pain.

2. Discuss the various causes of the opioid crisis in the United States.

3. Create a plan for postoperative pain management with a patient planning a major surgical procedure.

4. Evaluate pain, function, and comorbidities in patients taking opioids.

5. Recognize and manage opioid-induced hyperalgesia.

Summary

Opioid crisis: United States makes up 5% of world population but consumes 99% of world’s production of hydrocodone and 85% of oxycodone; 80% of new abusers of heroin start with prescription opioids; opioids among most commonly prescribed drugs in United States; hydrocodone/acetaminophen third-most-prescribed drug in US (by number of prescriptions written); time-release oxycodone (OxyContin), first available in 1996, became most abused drug in world; deaths — military veterans (many of whom have chronic pain as result of their service) twice as likely as general population to die from opioid overdose; most abuse and fatal overdoses occur among rural, white Americans without college degrees, who may have lost their jobs; rate high in Appalachia (highest in West Virginia); ≈64,000 deaths from drug overdose reported in 2016 (21% increase over 2015); two-thirds involved prescription opioids, illicit opioids, or both (increase of 28% compared with 2015); in 2016, thousands more individuals in US died from overdoses than died in entire Vietnam War; in second quarter of 2017, 1 in 6 visits to emergency departments related to opioids; 10% fewer opioid prescriptions written in 2017; crisis affects individuals of every age

Etiology of opioid crisis: in 1990s, clinicians began treating pain as serious medical issue; they were encouraged by pharmaceutical companies to prescribe pain medications despite only minimal evidence that opioids effective for chronic pain; 1980 letter in New England Journal of Medicine stated that development of addiction in response to treatment with narcotics rare in patients without history of addiction; number of prescriptions for painkillers increased dramatically throughout 1990s; Purdue Pharma heavily promoted oxycodone (OxyContin formulation), leading to more prescriptions; company later fined for misbranding drug and downplaying risk; in 2017, Tom Frieden (then director of Centers for Disease Control and Prevention [CDC]) wrote in New England Journal of Medicine that data on long-term use of prescription opioids inadequate; most trials have lasted ≤6 wk; several show that long-term use of opioids actually worsens pain (perhaps by increasing perception of pain [leading to hyperalgesia]); rate of opioid dependence may be 26% among patients using opioids for chronic noncancer pain; 1 in 550 patients who starts opioid therapy dies of opioid-related cause at median of 2.6 yr after first prescription

Role of Congress: 2016 law made it more difficult for Drug Enforcement Agency (DEA) to fine manufacturers and wholesalers; made it virtually impossible to freeze suspicious narcotics shipments; political action committees and drug companies made campaign contributions to senator and congressman who sponsored legislation; overall, industry spent $106 million lobbying for bill; law firms and pharmaceutical companies hire officials previously employed by DEA in hopes of forming political alliances; since 2011, DEA has levied fewer suspensions and fines of doctors, pharmacies, drug companies, and wholesalers

Proposed legislation: many bills being considered to address opioid crisis; proposed legislation includes payment of loans for clinicians who specialize in addiction, efforts to streamline prescription drug monitoring programs across 50 states, identification of high-volume prescribers, and support for buprenorphine

Looming consequences for manufacturers: many states, and many more cities, are suing several pharmaceutical manufacturers of controlled substances; some companies no longer promoting these drugs

Heroin: price of heroin falling, and prices of prescription opioids rising; heroin easier to obtain, and therefore replacing other opioids; risk factors for long-term use of heroin include abuse of alcohol, marijuana, cocaine, and especially prescription painkillers; antecedent use of prescription opioids main reason individuals become addicted to heroin

Duration and dosing: number of morphine milligram equivalents (MMEs) prescribed per individual prescription in United States increased from 180 in 1999 to 640 in 2015; even at low doses, taking opioids for >3 mo increases risk for addiction 15-fold; CDC recommends that for most patients, opioids for acute pain should be given for ≤3 days

Dosing and risk: dose of 50 MME per day doubles risk for death from overdose, and 90 MME associated with 10-fold increase in risk (compared to 20 MME per day); patient with prescription for ≥50 MME should also be prescribed naloxone (Narcan) when opioid dispensed; patients who overdose die of respiratory depression; lowest effective dose should be given; some pharmacy benefit managers limit number of doses and total daily dose

Synthetic opioids: fentanyl and its derivatives currently driving deaths from opioids; illegal fentanyl killed half of those who died from opioid overdose in 2016; deaths from fentanyl overdose increased 540% in 3 yr; most potent analogs included carfentanil (tranquilizer used for large animals); carfentanil 100 times more potent than fentanyl, and fentanyl 100 times more potent than morphine; carfentanil being used to cut heroin; tiny amount of carfentanil may cause death; some of these drugs now replacing heroin

Sources of opioids: most users acquire prescription drugs (54% obtained drug from friend or relative); recreational users may mix drugs or combine them with alcohol, producing lethal outcomes; leftover opioids should be secured or removed from home

Risk for overdose per quantity prescribed: study evaluated 1- and 3-yr probabilities of continued opioid use among opioid-naïve patients, by quantity given as first prescription; when 5 days’ supply given, risk for continued use at 1 yr 10%; risk doubles when 10-day supply given, and rises to 25% for 2-wk supply and 35% for 30-day supply; study also assessed probabilities of continued use based on number of prescriptions (in first episode of use); when 2 prescriptions given, risk for continued use at 1 yr 15%; when 6 prescriptions given, risk >50%, and when 12 refills given, risk 90%; CDC recommends that for acute pain, quantity of medication given should match expected duration of more severe pain; medication for 3 days often sufficient; opioids rarely needed for >7 days; dose of ≥50 MME/day doubles risk compared with 20 MME/day; most patients do not need >20 MME/day

Postoperative opioids: data from Department of Defense Military Health System Data Repository used to study 215,000 opioid-naïve patients 18 to 64 yr of age who underwent common surgical procedures and filled ≥1 prescription for opioid within 14 days of procedure; 19% received single refill; median quantity of drug adequate to cover 4 days of use and ranged as high as 7 days for discectomy; proportions of patients receiving refills ranged from 11.3% after cholecystectomy to 39% after repair of anterior cruciate ligament; median time to refill 6 days; authors concluded that 7 days of medication adequate after most common procedures, and 10 days sufficient after common neurosurgical and musculoskeletal procedures

Comparison of analgesic medications: study evaluated 416 patients 21 to 64 yr of age; patients treated in emergency departments for moderate to severe pain in extremity and randomized to 1 of 4 groups (400 mg ibuprofen plus 1000 mg acetaminophen [Aurophen, Cetafen, Tylenol]); 5 mg oxycodone plus 325 mg acetaminophen; 5 mg hydrocodone plus 300 mg acetaminophen; or 30 mg codeine plus 300 mg acetaminophen); primary outcome decrease in pain 2 hr after ingestion, on scale of 0 to 10; 1.3 points on pain scale considered minimum clinically important difference; at baseline, mean pain score 8.7; decreases in pain scores 4.3 in ibuprofen-acetaminophen group, 4.4 in oxycodone-acetaminophen group, 3.5 in hydrocodone-acetaminophen group, and 3.9 in codeine-acetaminophen group; study suggests that opioids not significantly more effective than ibuprofen

Treating pain after discharge from hospital: another study assessed 333 hospitalized patients; on day of discharge, quantity of outpatient opioids prescribed was based on amount used during hospitalization (eg, patients who took no opioids before discharge received none; patients who took 1 to 3 doses on day before discharge received 15 doses, and those who took 4 doses on day before discharge received 30 doses); found that older patients took fewer doses; patients <60 yr of age took mean of 13 doses after discharge, while those ≥60 yr of age took mean of 4 doses; 38% of dispensed doses taken

Recommendation for treating acute pain (UpToDate, 2017): acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen sodium, or celecoxib usually provide adequate relief when given alone or in combination for mild to moderate pain; ibuprofen and naproxen sodium associated with rapid onset of effect; treatment usually more effective when given on regular schedule; NSAIDs may be more effective than acetaminophen for some types of pain (eg, dental pain); combination treatment may be more effective than either drug alone

Choosing opioid and dose (UpToDate, 2017): whether considering efficacy or tolerability, few data support choosing one opioid over another; when combined with acetaminophen or ibuprofen, equally efficacious doses include 5 mg oxycodone, 5 mg hydrocodone, 30 mg codeine, and 50 mg tramadol; codeine should be avoided because of interpatient variability; codeine is prodrug (metabolized by cytochrome P450 2D6 to morphine); rapid metabolizers (eg, many children) at higher risk for overdose, and poor metabolizers may not experience relief of pain

Government limits on prescriptions: South Carolina now limits initial opioid prescription for acute and postoperative pain to maximum of 5 days for Medicaid recipients, and state’s Public Employee Benefit Authority enacted similar limits; Centers for Medicare and Medicaid Services considering 7-day limit for patients on Medicare, with dose limited to ≤90 MME/day; Medicare Part D may add monitoring for misuse of opioids, especially in patients also using gabapentin, pregabalin, or benzodiazepine

Type of opioid: short-acting opioids preferred for treating acute pain; long-acting drugs too slow to reach steady state and cannot be used for treating breakthrough pain; unintentional overdose 5 times more likely with extended-release than immediate-release opioids

Goal for pain control: should be realistic; goal not to eliminate pain, but rather to achieve 3- to 4-point reduction in baseline pain score without causing impairment; pain and function should be evaluated in patients on opioids using pain score and PEG score (pain, enjoyment of life, and general activity)

Respiratory depression: patients and caregivers should be educated on respiratory depression; patient should be monitored for sedation or confusion, respiratory rate <12 breaths/min, shallow breathing, increased snoring, decreased arousability, and pinpoint pupils; naloxone should be given to patient with concerning signs; patient on long-term opioids (especially doses ≥50 MME) should be provided with naloxone; naloxone available without prescription in some states

Opioids for noncancer pain: Cochrane review found that opioids more effective than placebo for hip or knee pain and offer modest improvement in function; patients with back pain twice as likely to not return to work if opioids prescribed; no differences found between high and low doses; opioids not well tolerated; no data show that opioids safe and effective for chronic noncancer pain

Psychiatric comorbidities; common in patients who overdose or abuse opioids, including depression in 30% to 50%, anxiety disorders in 16% to 50%, and personality disorders in 30% to 80%; clinician should screen for psychosocial issues and psychiatric disorders before prescribing opioids

Efficacy: 2 small studies evaluated long-term use of opioids for noncancer pain; only 44.3% of patients had ≥50% reduction in pain, indicating that opioids not effective over long term; SPACE trial (2018) studied 240 patients with chronic pain in back, hip, or knee; over 1 yr, treatment with opioids not superior to treatment with nonopioid medications; results did not support initiation of opioids for moderate to severe chronic pain from osteoarthritis

Assessing PEG score: 3-question instrument should be administered at each visit; goals to treat pain, improve activity and function, and avoid impairment from side effects of drug

Pearls for safe prescribing: preventing overdose — short-­acting opioids preferred; overdose more likely during first 2 wk of treatment in patients taking extended-release opioids than in those on short-acting drugs; risk for overdose depends on MMEs; CDC published checklists for prescribing opioids for chronic pain; risk for overdose increases dramatically when opioids combined with benzodiazepines; opioid-induced hyperalgesia — patient who does not receive expected benefit from opioids may have opioid-induced hyperalgesia; hyperalgesia improves when opioids tapered; hyperalgesia side effect of opioids, especially in patients on higher doses; switching opioids — when opioid rotation being initiated, same MMEs should not be prescribed; instead, starting dose of new agent should be given; when switching agents, clinician should begin with at least 50% fewer MMEs (patient who has not developed cross-tolerance may experience respiratory depression); increasing dose — doses of opioids should not be increased at bedtime; dose increases should be initiated in morning; naloxone — nasal spray preferred route for naloxone; 2 doses cost $135; in contrast, 2 doses of autoinjector cost $4000; household safety — takeback programs safest way to reduce opioids in households; available in some pharmacies; alternatively, powder (DisposeRx) may be mixed with water and opioid to form gel that may be safely discarded

Readings

Suggested Reading

Chang AK et al: Effect of a single dose of oral opioid and nonopioid analgesics on acute extremity pain in the emergency department: a randomized clinical trial. JAMA 2017 Nov 7;318(17):1661-7; da Costa BR et al: Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev 2014 Sep 17;(9):CD003115; Dahan A et al: Incidence, reversal, and prevention of opioid-induced respiratory depression. Anesthesiology 2010 Jan;112(1):226-38; Dowell D et al: CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep 2016 Mar 18;65(1):1-49; Dunn KM et al: Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med 2010 Jan 19;152(2):85-92; Fischer-Kern M et al: The relationship between personality organization and psychiatric classification in chronic pain patients. Psychopathology 2011;44(1):21-6; Hill MV et al: Guideline for discharge opioid prescriptions after inpatient general surgical procedures. J Am Coll Surg 2018 Jun;226(6):996-1003; Krebs EE 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 Mar 6;319(9):872-82; Ladapo JA et al: Physician prescribing of opioids to patients at increased risk of overdose from benzodiazepine use in the United States. JAMA Psychiatry 2018 Jun 1;75(6):623-30; Miller M et al: Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy. JAMA Intern Med 2015 Apr;175(4):608-15; Noble M et al: Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev 2010 Jan 20;(1):CD006605; Scully RE et al: Defining optimal length of opioid pain medication prescription after common surgical procedures. JAMA Surg 2018 Jan 1;153(1):37-43; Seth P et al: Overdose deaths involving opioids, cocaine, and psychostimulants — United States, 2015-2016. MMWR Morb Mortal Wkly Rep 2018 Mar 30;67(12):349-58; Shah A et al: Characteristics of initial prescription episodes and likelihood of long-term opioid use — United States, 2006-2015. MMWR Morb Mortal Wkly Rep 2017 Mar 17;66(10):265-9.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Weart was recorded at Evidence-Based Drug Therapy Update, presented by the Medical University of South Carolina, College of Medicine, Office of Continuing Medical Education, and held May 24-26, 2018, in North Charleston, SC. For information on upcoming CME activities presented by the Medical University of South Carolina, please visit www.musc.edu/cme. The Audio Digest Foundation thanks Dr. Weart and the Medical University of South Carolina for their cooperation in the production of this program.

CME/CE INFO

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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 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Lecture ID:

IM653201

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.