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Opioid Prescribing: Calculating Risk in the Context of Today's Crises

Opioid Prescribing: Calculating Risk in the Context of Today's Crises

A PAINWeek 2021 meeting highlight featuring Kevin Zacharoff, MD, and Jeffrey Fudin, PharmD


What, exactly, is opioid risk?

This was the question posed by Kevin Zacharoff, MD, FACIP, FACPE, FAAP, clinical instructor and course director of pain and addiction at the Renaissance School of Medicine at Stonybrook University when he opened his talk, "2+2 Before: Using 'New Math' to Calculate Opioid Risk," at PAINWeek 2021.

It depends on who you ask, he told the audience.

Risk, itself, of course, is easy to define—the possibility of something bad happening.

And the opioid overdose crisis is well known to all clinicians, whether in general practice or specialty care. In 2019, more than 70,000 people died from drug overdose, and 1.6 million had an opioid use disorder in the past year.1

However, ''the word opioid risk has taken on a new meaning," Dr. Zacharoff said. When opioid risk is discussed and considered by clinicians, these days, not only must adverse effects on a patient level be addressed, he noted, but also many other types of risk, including:

  • Tolerance and dependence 
  • Unhealthy use
  • Aberrant drug-related behavior
  • The opioid epidemic
  • Regulatory risk
  • Societal risk

Opioid Prescribing: Assessing Patient Level Risks

On the patient level, said Dr. Zacharoff, it's important for clinicians to be aware of the many potential adverse effects when prescribing opioids, including constipation, nausea and vomiting, dry mouth, itching, sweating, imbalance of the endocrinopathy/hormonal axis, immunosuppression, sleep disturbance, and respiratory depression.2

Several risk factors for potential opioid-related adverse effects have been identified, including:

  • A history of nausea and vomiting with opioid therapy
  • Chronic constipation
  • Itching, flushing or histamine release
  • Obstructive sleep apnea
  • Morbid obesity
  • COPD
  • Use of other CNS depressants.3

Dr. Zacharoff also addressed how to distinguish opioid risk from opioid complication and/or adaptation. “Tolerance,” for instance, he said, is a state of adaptation in which longer-term exposure leads to lower analgesic effect, leading patients to needg higher doses to achieve therapeutic goals. Physical or physiologic “dependence” is a also a state of adaptation in which longer-term exposure leads to the manifestation of withdrawal symptoms or syndrome when there is abrupt discontinuation, rapid dose reduction/tapering, or administration of an agonist.3

Unhealthy use practices are yet another risk clinicians must address. Dr. Zacharoff defined these as such:

  • Misuse: the use of a medicine for a purpose other than as directed or indicated. Use can be willful or not, with harmful results or not.
  • Abuse: any use of an illegal drug, or intentional use of a medication for a nonmedical purpose, such as getting high.
  • Addiction: a primary, chronic disease involving brain reward, motivation, memory and related circuity that can lead to relapse and progressive development and that is potentially fatal when untreated. Craving and continued use despite adverse outcomes are part of the definition.4

(More on the distinctions between addiction and dependence)

Editor’s Note on Terminology: Of note, the National Institute on Drug Abuse (NIDA) points out that the term “misuse” – that is, consumption outside prescribed parameters – should be used instead of “abuse” when talking about prescribed drugs due to negative associations with the word  “abuse.” When talking about illicit drugs, the term is simply “use.” NIDA also uses “misuse” and “nonmedical use” interchangeably as we do herein. SAMHSA differentiates the terms as well, utilizing “misuse” for prescription drugs and “abuse” for illicit drugs. 

Dr. Zacharoff further described unhealthy use of opioids when it comes to undertreated pain, questioning whether this carries risk. Federal data show that most people who use prescription pain relievers "'nonmedically" get them from friends or family with a valid prescription. Untreated pain, on the other hand, can reduce quality of life, impair physical function, burden people financially, result in physical disability and be linked to depression, anger, anxiety, fear and reduced social capacity.4

When considering the risk of unhealthy use of opioids, these risk factors have been found:

  • Younger age
  • Pain-related disability
  • Catastrophizing
  • Fear related to unknown pain etiology
  • Low social support
  • Personal or family history of substance abuse
  • History of trauma and stress4

Clinicians can and should therefore screen for unhealthy drug use in adults 18 years and older, regardless of risk factor, by asking questions.

Among Dr. Zacharoff's suggestions for mitigating patient-level opioid risk are paying adequate attention to the initial assessment to determine whether opioids are clinically indicated and to look at specific risks in individual patients. Screen for unhealthy use, monitor for aberrant behaviors, he noted. Consider opioid rotation, dose reduction, tapering, or discontinuation. Clinicians must also address safe storage and disposal, as well as a patient's responsibilities taking the medications (see our Clinician Guide on drug monitoring and medication adherence).

Opioid Prescribing: Current Regulatory Risks

Part of the “new math” involved in prescribing opioids can be a regulatory risk. "When we prescribe an opioid, we have to be looking over our shoulder," Dr. Zacharoff told PPM after his talk,and that's because state medical boards and other regulatory agencies are watching. Opioid treatment may be considered inappropriate if it lacks enough initial pain assessment, risk determination, inadequate monitoring, inadequate patient education, or other parameters.

"Investigators are going back 3 years to identify any doctors who may have prescribed the drugs inappropriately when someone dies of an overdose death, even if it was not the fatal dose, and send them letters," he told the PAINWeek audience. He further shared this illustration of how important attention to detail is. "A physician in San Francisco was sent a letter explaining that a patient he had treated died in 2012 from taking a toxic cocktail of methadone and Benadryl–and he was the doctor who wrote the patient's last prescription for methadone." The physician had just 2 weeks to respond with a written summary of the care he had given and a certified copy of the patient's medical record, with $1,000 daily fines for noncompliance.

Opioid Prescribing: Societal Risk

Determining opioid risk also means clinicians must pay attention to the family of the patient and its role in proper medication adherence, including intake of opioid analgesics and potential diversion. Clinicians should counsel adult patients given these drugs about the risks of them to youth in the house as well.

Practical Takeaways

"I think it's really important that clinicians don't look at this as being too complicated, and step off [from caring for the patient], " Dr. Zacharoff told PPM. "It can get complicated," he admits. But it's easier, he said, ''if we remember we are doing all this for the benefit of the patient, we are doing it for the benefit of society. We have a responsibility as a prescriber of opioids to do what's right for the patient but also to understand all the other areas of society that could be impacted by risk."

Dr. Zacharoff’s session "did an excellent job in carefully outlining many of the factors that are, more often than not, left out of the 'equation' when considering real life influences on opioid risk," said Jeffrey Fudin, PharmD, DAPM, FCCP, FASHP, PPM’s Co-Editor-at-Large. " From my experience, it is clear that [some] prescribing clinicians have simply chosen not to prescribe opioids in patients that require them, leading to patient abandonment and subsequent intolerable pain, anxiety, depression and suicide.”

"Dr. Zacharoff’s insight should help clinicians appreciate the multifactorial analysis that is necessary for each patient as an individual rather than leaving opioid prescribing to 'the next guy' to avoid liability – that unfortunately places patients in the crossfire of a political debate rather than embracing the issues and helping the patient and their caregivers.”  



  1. SAMHSA. 2019 National Survey on Drug Use and Health, 2020. Available at: https://nsduhweb.rti.org/respweb/homepage.cfmAccessed September 2021.
  2. NIDA. Prescription Opioid Drug Facts. Available at: www.drugabuse.gov/publications/drugfacts/prescription-opioids Accessed Septemebr 2021.
  3. Jamison RN, Mao J. Symposium on Pain Medicine. Opioid Analgesics. Mayo Clin Proc. 2015l 90(7):957-968.
  4. Webster LR. Risk Factors for Opioid-Use Disorder and Overdose. Anesthesia & Analgesia. 2017.125:5:1741-1748
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