Martine Seudeal, MD

Robert Cannon, PhD

 

What are opioids?

Opioids are a class of drugs, composed of chemical compounds that act on mu, kappa, and delta-opioid receptors of the body to inhibit transmission of pain perception and subsequently produce analgesic (painkilling) and central nervous system depression; a common effect of opioids is euphoria.1 Some legal opioids include: codeine, hydrocodone, morphine, oxycodone, hydromorphone, and fentanyl; some illegal opioids include heroin and carfentanil.2 Opioids are most commonly used to treat pain.

Other approaches to treating pain include: physical medicine, behavioral medicine, neuromodulation, interventional and surgical approaches. Outcomes of pain management are often more successful when used in combination, and by a multidisciplinary team.3 An example of this could be a postoperative hip replacement patient receiving PRN (as needed) opioid pharmacotherapy prescribed by the orthopedic surgeon, in combination with physical therapy, done by a group of physical therapists. The two most common and appropriate scenarios that necessitate the use of prescribed opioids are for relief from cancer-related and post-operative pain. The use of opioids for the management of chronic non-cancer pain has increased in the last 20 years.4

When taken for short periods of time, opioids can aid in relief from acute and chronic pain; discretion is used by the physician when prescribing these drugs, based on each patient case. Long-term use of opioids can result in physical dependence, and withdrawal symptoms (when the opioid is stopped) include: “restlessness, muscle and bone pain, insomnia, diarrhea, vomiting, cold flashes, and involuntary leg movements”.8

 

Opioid Crisis Progression:

As of June 2017, more than 90 Americans die of opioid overdoses on a daily basis; this is from legal (prescribed), as well as illegal opioids.5 The CDC has estimated that the misuse of prescription opioids costs $78.5 billion dollars per year; this includes the cost of healthcare (including the treatment of neonatal abstinence syndrome, secondary to use during pregnancy, and the spread of HIV and hepatitis C), lost wages, treatment for addiction, and legal fees. Opioids began to be prescribed in the late 1990s due to reassurance for pharmaceutical companies that these medications were not addictive. As opioids became more widely used, and more people became addicted, the rates of overdose increased.

By 2015, more than 33, 000 Americans died due to opioid overdoses; approximately 2 million people in the United States suffered from opioid (legal and illegal) addiction, and 591, 000 Americans were using heroin. Approximately 21-29% of patients who were prescribed opioids for chronic pain have misused them, and between 8-12% will go on to develop an addiction. 4-6% of patients who misuse their prescription opioids will transition to heroin use; approximately 80% of heroin users began by first misusing prescription opioids.5

OxyContin (oxycodone) was approved for prescription use by the FDA in 1995. 1n 1996, pain was described as a fifth vital sign, with the intention of treating it, as one would treat blood pressure or heart rate. These changes coincided with a time period when medical professionals recognized that pain was often inadequately treated. According to the Tennessean, Purdue Pharma, a manufacturer of OxyContin, introduced an extensive marketing campaign at this time, aimed at doctors; advertisements were placed for OxyContin in medical journals, promotional conferences were done, and pharmaceutical representatives were sent to physicians’ offices and clinics around the country.

In 1999, 5% of patients who received publicly funded addiction treatment (in Tennessee) were abusing pain relievers. In 2003, the FDA sent a “warning letter” to Purdue Pharma, acknowledging that they had failed to disclose OxyContin’s potential for abuse and adverse effects. By 2011, Lortab (acetaminophen and hydrocodone) became the most commonly prescribed controlled substance in Tennessee; the cost of insurance claims during this period, for this specific drug, was $6.8 billion dollars. In 2002, the Prescription Safety Act was passed; this required health care providers to register patients who received more than 15 days of prescription opioids; before refilling a more than 7 day supply, doctors are required to check this registry, in an effort to track and deter patients who were “doctor shopping”.6

Another issue that arose from the widespread use of opioids was the risk of pregnant users giving birth to opioid-dependent babies. In 2013, all drug-dependent babies were required to be registered with the Tennessee Department of Health, under the diagnosis of “neonatal abstinence syndrome”; 912 drug-dependent babies were reported that year. 41% of the women who had given birth to drug-dependent babies took prescribed painkillers. That same year, 1, 166 people in Tennessee died of complications from opioids (more than motor vehicle accidents, homicides, or suicides combined). During July of 2014, doctors in Tennessee were allowed to begin prescribing naloxone, an opioid antidote. Police were also trained to administer naloxone, but 1,263 deaths from opioid overdoses were still reported in Tennessee.6 Other antidotes for opioid reversal include methadone and buprenorphine.7

Despite these staggering figures, in 2015, Tennessee physicians wrote more than 7.8 million prescriptions for opioid (equivalent to 1.18 prescriptions for every person, including children, in their state). According to the Tennessee Department of Mental Health and Substance Abuse Services, 55% of opioid abuses receive these drugs from a family member or friend who has a prescription.6

 

Utility of Opioids:

            Short-acting opioids, such as meperidine (Demerol), hydromorphone (Dilaudid), morphine, oxycodone, oxymorphone, tapentadol, and tramadol can be prescribed for acute pain; the rationale for use in the acute setting, as opposed to chronically, would be the risk reduction of central nervous system toxicity and efficacy. Long acting opioids, such as buprenorphine (Butrans, patch), fentanyl (Duragesic, patch), hydrocodone ER (Zohydro ER), hydromorphone ER (Exalgo), methadone, morphine sulfate ER (Kadian, Contin), oxycodone ER (OxyContin), oxymorphone ER (Opana ER), tapentadol ER (Nucynta ER), and tramadol ER (Ultram ER).

Indications for opioid therapy in the treatment of chronic non-cancer pain include: other therapies have failed to provide sufficient pain relief, AND pain is “adversely affecting” a patients quality/function of life, AND the potential benefits of use outweigh the potential harms. As stated previously, opioids should be prescribed in combination with non-opioid pharmacotherapy, as well as non-pharmacotherapy to achieve adequate pain control and with the goal of using the lowest effective doses of opioids.3

A group of surgeons at the University of Michigan has begun to take measures of their own to ameliorate the opioid crisis. Their strategy is to prescribe a smaller quantity of opioid pills postoperatively. This, in combination with a detailed patient-physician discussion of the risks of opioid use (addiction and overdose), could produce changes in the future of the opioid crisis.9 An example of this would be a postoperative cholecystectomy (gallbladder removal) patient receiving opioid painkillers while in the hospital, only as needed, and the physician gauging their pain tolerance and response to these medications; upon discharge from the hospital, the physician has had a discussion with the patient about the necessity (or not) for opioid medications at home and an agreement is made between the physician and patient on how many pills will be prescribed. Many times opioids are currently distributed postoperatively based on how many pills a patient could potentially consume in a certain time period, for a certain predicted period of time in which the patient will experience pain, without overdosing.

For example, Tylenol 3 (acetaminophen and codeine) is a common opioid combination prescribed for at-home use after surgery. One to two Tylenol 3 (300 mg-15 mg) pills can be taken every 4 hours as needed for pain for 7 days; when writing the prescription, the maximum number of pills that can be distributed is 42. Often times, the physician assumes that the patient will need 42 pills, and writes “#42”, but how would the physician know if this patient would necessitate pain medication for 7 whole days? Should the prescription specify that Tylenol 3 be used for severe or moderate pain, as opposed to mild pain (in which case, a non-opioid can be used)? A simple discussion about pain control prior to the surgery, and as the postoperative time period unfolds, could answer some of these questions.

At Michigan’s University Hospital, 170 postoperative cholecystectomy patients were surveyed within a year of their surgery and asked how many opioid pills they used, what type of pain they had after their surgeries, and whether or not they had other non-opioid options for pain control. Based on the results of this survey, new guidelines were formed to enable the reduction of opioid prescriptions after cholecystectomies. The guidelines were enforced and there was a reduction in the number of pills prescribed to each patient in a 200 postoperative patient pool. The end result was that despite being prescribed fewer pills, patients did not report higher levels of pain, and were not more likely to ask for refills. This not only prevents future addiction, but also reduces misuse and potential recreational use. Other strategies for reducing the use of opioid painkillers include: promoting the use of lower-strength non-opioid painkillers as a first option, discussing the risks of addiction, and reminding patients that postoperatively, they may still experience some pain, despite opioid painkillers.9

 

Misuse of Opioids:

Prior to initiating therapy with an opioid drug, screening is done to determine a patient’s risk of misuse; the CDC has released a general checklist to aid in rapid screening. Risk factors for opioid overdose include: prescription of higher than average daily doses, multiple prescriptions from multiple prescribers, prolonged use, the use of longer acting opioids, a history of prior overdose, concomitant use with benzodiazepines, male gender, Caucasian race, age 30-54, residence in an urban county, lower income, and history of prior substance abuse or psychiatric disorder.3

A patient who will initiate opioid therapy must be screened for potential abuse or misuse and risk stratified. A discussion about patient responsibilities (taking medications only as prescribed), risks of therapy (adverse effects and addiction), and treatment goals is necessary. A written consent should be signed, acknowledging this agreement between the physician and patient. After initiation of therapy, routine follow up should be done by the prescribing physician, and periodic drug screens should be performed to ensure that medications are being taken.3

            A study done by Zirui Song (assistant professor of healthcare policy at Harvard Medical School) in 2016 showed an increase in the number of opioid-related deaths in hospitals by almost 4 times, from 1993 to 2014. This includes deaths related to legal opioids or heroin use. The average age of patient dying from an opioid-related cause was found to be 39 years old. The number of black and Hispanic patients admitted for opioid/heroin overdose remained steady from 1993-2014, but the number of white patients admitted for these overdoses doubled between 2007 and 2013. This demonstrated that there is a necessity for “continuing and improving public health and community strategies”.10

 

A Middle Ground:

While there are clear indications for the use of opioid drugs, the public health and economic crisis that has arisen from use has sparked a plethora of strategies to reverse and prevent adverse outcomes of opioid use. Palliative, cancer, and post-operative are the main groups of patients who will necessitate opioid drugs. As pain is now considered a fifth vital sign, it is unreasonable in these scenarios to withhold adequate pain control, due to the risk of addiction, abuse/misuse, or overdose.

When prescribing opioid drugs, a clear discussion between the physician and patient should be held before initiating these medications, and both parties should sign a written consent. If the patient is admitted to the hospital, a trial of the minimum quantity of medication to control pain can be done, before discharging the patient with the maximum number of pills allowed.

Pain control can be achieved using not only opioid drugs as monotherapy, but instead in combination with other pharmacologic and non-pharmacologic therapy. Close follow up by the prescribing physician is crucial to ensure that these medications are not being abused. In an outpatient setting, it is reasonable to exhaust various remedies (non-opioids, physical therapy, heat therapy, etc.) before initiating opioid therapy for pain control.

Physicians should adhere to placing their patients on a national registry, to ensure that they are not receiving multiple prescriptions for opioid drugs; urine drug screens during routine follow up visits can also ensure that the patient is actually taking their medication.

References

  1. Strain, Eric. “Pharmacotherapy for opioid use disorder.” UpToDate, 4 Dec. 2017, www.uptodate.com/contents/pharmacotherapy-for-opioid-use-disorder?source=search_result&search=pharmacotherapy%20for%20opioid%20use%20disorder&selectedTitle=1~150.
  2. Rosenquist, Ellen WK. “Overview of the treatment of chronic non-Cancer pain.” UpToDate, 30 Nov. 2017, www.uptodate.com/contents/overview-of-the-treatment-of-chronic-non-cancer-pain?source=search_result&search=treatment%20of%20chronic%20non%20cancer%20pain&selectedTitle=1~150.
  3. Steven Melemis, I Want to Change My Life. “Opioids – Opiates: Addiction, Withdrawal, Crisis, Recovery Facts.” I Want to Change My Life, www.addictionsandrecovery.org/opioid-opiate-recovery.htm.
  4. Gupta , Anita, and Richard Rosenquist. “Use of opioids in the management of chronic non-Cancer pain.” Use of opioids in the management of chronic non-Cancer pain, UpToDate, 18 Oct. 2017, www.uptodate.com/contents/use-of-opioids-in-the-management-of-chronic-non-cancer-pain?source=search_result&search=use%20of%20opioids%20in%20the%20treatment%20of&selectedTitle=1~150.
  5. Abuse, National Institute on Drug. “Opioid Overdose Crisis.” NIDA, 1 June 2017, drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis.
  6. Wadhwani, Anita, and Ayrika L Whitney. “Timeline: How the opioids crisis took hold.” Timeline: How the opioids crisis took hold, The Tennessean, 2017, www.tennessean.com/story/news/2017/04/08/timeline-how-opioids-crisis-began-took-hold-tennessee/98866140/.
  7. Abuse, National Institute on Drug. “Overview.” NIDA, www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/overview.
  8. “Talking with Your Healthcare Provider.” Talking with Your Healthcare Provider | NIH MedlinePlus the Magazine, medlineplus.gov/magazine/issues/spring11/articles/spring11pg8.html.
  9. Luthra, Shefali. “Surgeons Try Prescribing Fewer Opioids To Lower Addiction Risk.” NPR, NPR, 6 Dec. 2017, www.npr.org/sections/health-shots/2017/12/06/568806212/surgeons-try-prescribing-fewer-opioids-to-lower-addiction-risk.
  10. Santhanam, Laura. “Deaths during opioid-Driven hospital stays have quadrupled.” PBS, Public Broadcasting Service, 4 Dec. 2017, www.pbs.org/newshour/health/deaths-during-opioid-driven-hospital-stays-have-quadrupled.

 

SHARE