By Howard Marcus, MD, FACP

Opioids play an important role in pain management—both in acute and chronic settings. Prescribing safely is a laudable goal for healthcare providers, especially considering that 60 percent of Americans over age 65 seek relief from persistent pain. However, the dramatic increase in opioid use over the past few decades has resulted in an opioid-related epidemic of addiction and death. There has also been substantial misuse of opioids obtained by diversion—that is, by a person for whom they were not prescribed.

Consider these facts:

• The United States consumes 99 percent of the world's hydrocodone.
• The number of annual opioid prescriptions written in the United States is roughly equal to the number of adults in the country.
• Nine million Americans take prescribed opioids on a long-term basis.
• Five million Americans report nonmedical use of opioids without a prescription.
• Nearly 60 percent of Americans have leftover opioids in their homes, and 20 percent have shared their opioids with others, often to help with pain management.
• Thirty-eight percent of teens have misused or abused prescription drugs obtained from the home medicine cabinet.
• One of every 550 patients started on opioid therapy died of opioid-related causes a median of 2.6 years after the first prescription.
• In 2015, 19,000 Americans died of an opioid overdose, and the death rate from all opioids (including heroin) now exceeds the death rate from motor vehicle accidents.
• Opioid diversion is an enormous problem. About 50 percent of opioid-related deaths are caused by opioids obtained from a family member or friend.

Poor patient outcomes related to opioids are a common cause of litigation. The Doctors Company studied 272 claims that closed between 2007 and 2015 in which opioids resulted in patient harm. Contributing factors included:

• Inappropriate selection and management of therapy.
• Errors in patient monitoring.
• Inadequate patient assessment for risks and contraindications to opioids.
• Failure in communication among providers.
• Insufficient documentation and/or support for clinical decision making.
• Failure to take psychiatric and/or abuse history.
• Communication errors with patients and their families, including insufficient warning of risks of opioids.
• Patient factors, including noncompliance with treatment plans and follow-up appointments.

Prescription opioids (mu receptor agonists) are no less addictive than heroin, and the increase in prescription opioids fuels illicit drug use. The dramatic increase in heroin addiction and related deaths has accelerated as a result of the low street price of heroin, compared to the relatively high cost of Percocet (New York Times, June 14, 2016).

While physicians prescribe many medications with high risk/benefit ratios and a narrow therapeutic window, the high opioid complication rate is unique—largely because opioids induce euphoria, have a high potential for addiction, and have a therapeutic endpoint (i.e., suppression of pain) that is subjective. Healthcare providers must work to prevent opioid misuse and addiction while protecting the well-being of patients experiencing the devastating effects of acute or chronic pain.

In March 2016, the Centers for Disease Control and Prevention (CDC) published guidelines for prescribing opioids for chronic, noncancerous pain. The following is a distillation of these guidelines, with recommendations from other sources:

1. Document a detailed history, physical findings, and lab or imaging findings, and provide a diagnosis and rationale for pain management.
2. Establish realistic treatment goals for pain and function. Total cessation of pain is usually unrealistic, and improvement of function should be a focus of therapy.
   
   Consider alternatives to opioids: Nonpharmacologic treatment, such as physical therapy and nonopioid pharmacologic therapy, is preferred for chronic pain. Some conditions, such as headache, fibromyalgia, and peripheral neuropathy, are better managed with alternative medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, anticonvulsants, and serotonin–norepinephrine reuptake inhibitors (SNRIs).
   
   The FDA has approved nonopioid medications for chronic pain, including gabapentin (Neurontin), pregabalin (Lyrica), milnacipran (Savella), and duloxetine (Cymbalta).
3. Evaluate risk factors carefully when determining opioid dosing and to assess for contraindications for opioid use. Preexisting conditions that increase the risk of side effects and overdose include asthma, obstructive sleep apnea (OSA), and chronic obstructive pulmonary disease (COPD). Patients over age 65, patients with renal and hepatic disease, and elderly patients (at risk for falls) will likely require a reduction in starting dose.
   
   Beware of drug interactions, including antihypertensives, resulting in orthostatic hypotension, and tricyclics and anticholinergics, resulting in confusion and urinary retention. Beware of specific drug interactions, such as with fentanyl and CYP-450 3A4 inhibitors (antifungals, erythromycin, and verapamil).
   
   About half of prescription opioid deaths involve at least one other drug, including benzodiazepine, cocaine, heroin, and alcohol. Whenever possible, avoid concomitant use of opioids with sedating drugs, such as benzodiazepines and muscle relaxants—particularly Soma—and caution against the use of alcohol.
4. Be aware that the risk of side effects, particularly respiratory depression, dramatically increases with doubling from 50 to 90 morphine milligram equivalents (MME) per day and increases ninefold at doses over 100 MME per day.
   
   Forty-seven states and the District of Columbia now have laws providing immunity to medical professionals who prescribe or dispense naloxone or individuals who possess or administer naloxone. Offer naloxone when prescribing doses over 50 MME/day or with concurrent benzodiazepine use.
5. Assess potential risk of opioid abuse. Red flags include tobacco use, family or personal history of substance and alcohol abuse, psychiatric disorders, and a history of sexual abuse.
   
   Use risk assessment tools, which may be available in your electronic health record. These types of tools include the following: Screener and Opioid Assessment for Patients with Pain (SOAPP); Diagnosis Intractability, Risk, Efficacy (DIRE); and Opioid Risk Tool (ORT).
   
   Start with the lowest effective dosage, and reassess before increasing the dose, particularly when prescribing for opioid-naive patients. Advise patients about potential side effects, including warnings about sedation and driving.
6. Always start pain management treatment with a short-acting opioid instead of an extended release (LA/ER) formulation. Avoid concomitant use of both short-acting and long-acting opioids.
   
   Consult the MME dosage tables when switching from one opioid to another. For example, conversion factors for oral daily dosing of the equivalent of morphine 30 mg are the following: oxycodone 20 mg, hydrocodone 20 mg, hydromorphone 7.5 mg. Note that fentanyl is 80 times more potent than morphine.
7. Use the lowest effective immediate-release dose when prescribing opioids for acute pain. A supply of more than seven days is rarely required, and a three-day supply is often sufficient. Massachusetts has established limits on dosing for acute pain and has enacted a law limiting an opioid prescription to a seven-day supply for first-time adult prescriptions.
8. Evaluate the benefit and harm within one to four weeks of starting opioid therapy. Reassess treatment goals at each visit, and consider reduction of the opioid dose when appropriate.
9. Consult the state prescription drug monitoring program (PDMP) when starting opioid therapy for chronic pain and periodically thereafter. Many states require consultation with the PDMP.
   
   Data from Kentucky demonstrates that since the state's PDMP mandate was implemented, there has been a 26 percent decrease in overdose hospitalizations and a 25 percent reduction in opioid-related deaths.
10. Use urine drug testing before starting chronic opioid therapy and at least annually to test for prescribed opioids, other controlled substances, and illicit drugs.
    
    Negative results on urine drug testing should raise concerns about diversion or maladaptive drug-taking behavior. Most drugs have a window of detection of about two days, although marijuana is detectable at a week. Oxycodone is not reliably detected by routine assay.
11. Advise patients to avoid and prevent opioid diversion. Store opioids in a location with limited access. Recommend that patients discard unused opioids by flushing them down the toilet, transferring them to police station receptacles, or turning them in at "take-back" events in the community.
12. Be aware of risk factors for opioid use in managing postoperative pain, particularly for respiratory depression in patients with diagnosed or suspected OSA, morbid obesity, COPD, heart disease, sedating drugs already in use, or those who use tobacco, are over 65 years old, have surgery with general anesthesia lasting more than six hours' duration, or have surgery performed on airway, upper abdominal, or thoracic regions.

Many state medical boards across the country require documentation of the following when prescribing opioids:

• An established physician-patient relationship.
• A history and physical, diagnosis of pain condition, objective studies, expectation of the treatment's effects, documentation of each prescription, and reasons for early refills and changes.
• A discussion of alternative therapies and substance abuse.
• PDMP consultation, urine drug screen, and an opioid contract.
• Monitoring the effectiveness of therapy, dependence, and withdrawal.

In summary, it is possible to prescribe opioids responsibly and safely for patients with chronic pain who do not obtain sufficient relief and reasonable function with nonopioid treatment. However, to do so, it is necessary to have adequate knowledge of the pharmacology of opioids, risk factors, and side effects. Safe opioid prescribing requires thorough patient evaluation, attention to detail, and familiarity with guidelines and regulations.

References

Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States. JAMA. 2016;315(15):1624-1645.

Frieden TR, Houry D. Reducing the risks of relief—the CDC's opioid prescribing guideline. N Engl J Med. 2016 Apr 21;374(16):1501.

Extended release/long acting opioids: achieving safe use while improving patient care. (CO*RE Collaboration for REMS Education 2013.)

Interagency guideline on prescribing opioids for pain. Olympia, WA: Washington State Agency Medical Directors' Group; 3rd Edition. 2015. www.agencymeddirectors.wa.gov/Files/2015AMDGOpioidGuideline.pdf.

Pevoznik T. The heart of safety. Paper presented at: 18th Annual NPSF Patient Safety Congress; May 23–25, 2016; Scottsdale, AZ.

Califf RM, Woodcock J, Ostroff S. A proactive response to prescription opioid abuse. N Engl J Med. 2016 Apr 14;374(15).

Renthal W. Seeking balance between pain relief and safety: CDC issues new opioid-prescribing guidelines. JAMA Neurol. 2016;73(5):513-514.

Vestal C. States require opioid prescribers to check for "doctor shopping." Stateline. Pew Charitable Trusts. May 9, 2016. www.pewtrusts.org/en/research-and-analysis/blogs/stateline/2016/05/09/states-require-opioid-prescribers-to-check-for-doctor-shopping.

Kennedy-Hendricks A, Gielen A, McDonald E, McGinty EE, Shields W, Barry CL. Medical sharing, storage, and disposal practices for opioid medications among US adults. JAMA Intern Med. 2016;176(7):1027-1029.

Ray WA, Chung CP, Murray KT, et al. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315(22):2415-2423.