The first recommendation suggests that chronic pain should be managed primarily with nonpharmacologic therapies and nonopioid pharmacologic therapies.32 Opioid therapy should be considered only when consideration given to both the potential benefit in pain control and functional improvement versus the risks. When opiates are used, they should be combined with nonopioid and nonpharmacological therapy.
Appropriate non-pharmacological therapies include weight loss, physical therapy, exercise, psychological therapies, and selected intervention procedures (joint injections). Nonopioid pharmacotherapy may include NSAIDs, acetaminophen, cyclo-oxygenase (COX)-2 Inhibitors, some anticonvulsants, and some antidepressants. The use of nonopioid pharmacotherapy is associated with a significantly reduced risk of overdose.32
The second recommendation suggests that before initiating opioid therapy in chronic pain patients, it is essential to establish realistic goals for pain and function.32 Also, patient education given that opioid therapy would discontinue if risks of therapy are deemed more significant than the benefits. Opioid prescriptions should only continue when there is a meaningful improvement in function and pain, and the benefit outweighs the risk to patient safety.
Research suggests that long-term use of opioids is associated with severe risks.32 Research shows weak evidence that opioid therapy beyond six months results in clinically significant pain relief or clinically significant improvements in quality of life. Many patients who use long-term opiate therapy discontinue therapy due to adverse effects or inadequate pain control. Because of these facts, it is hard to predict which patient will have benefits greater than harm when receiving chronic opiate therapy.
When opioid therapy initiated, the prescriber should determine the assessment protocol of the effectiveness of therapy. Also, treatment goals should be established with the patient before starting therapy.32 Goals should include relief in both pain and improvement in function. Conditions that lead to progressive functional impairment or injuries such as spinal cord trauma may have a primary goal of pain relief as opposed to improvements in physical function. Also, the consideration of the social and emotional well-being of patients should impact that assessment as well.
Functional goals may include returning to work, attending specific recreational activities, walking around the block, or taking the dog for a walk. Assessing for depression and anxiety as well as other psychological conditions is an important aspect of managing the whole patient. Generally, if pain and function are not improved on opioid therapy, tapering or discontinuing the opioid should be strongly considered.
A written agreement should also be used that discusses how opioids will be prescribed and monitored and how they will be tapered or discontinued.32 Situations, where opioids should be tapered or discontinued, include when opioids are not needed, side effects become too severe, or treatment goals not being met.
The third recommendation suggests that providers should discuss the risks and benefits of opioid therapy both before and during treatment. Also, the responsibilities of both patient and clinician merit mandatory discussion before and during therapy.32
Key teaching points32:
- Functional improvement is the primary goal, even if pain still is present
- The use of opioids generally does not improve pain and function in the long-term, but opioids may reduce pain in the short-term
- Discuss common side effects include nausea, vomiting, mental status changes, constipation, dry mouth, drowsiness, tolerance, physical and psychologic dependence, and withdrawal symptoms upon ceasing opioids
- Discuss potentially fatal respiratory depression, especially with higher doses or when used with other depressants such as benzodiazepines
- Chronic opioid use may lead to a lifelong opioid use disorder
- Increase fluid intake and fiber to reduce the risk of constipation
- Opioids reduce the ability to operate motor vehicles safely
- Discuss that the need for periodic review with consideration given to reducing or discontinuing the opioid
- Discuss the importance of not sharing prescriptions among family or friends
- Discuss safe storage, such as in a locked location
- Discuss the safe disposal of controlled substances
- Discuss monitoring that will include the use of urine drug testing and the use of the prescription drug monitoring program
- Consider discussing the use of naloxone
Recommendation four suggests that when starting opiates for chronic pain, immediate-release opioids are recommended over longer-acting drugs. Longer-acting opioids are associated with a higher risk of overdose when compared to immediate acting opioids.
The Food and Drug Administration (FDA) reported in 2014 that extended-release or long-acting opioid pain drugs should be used when pain is severe enough to necessitate daily, around the clock long-term opiate treatment when other options are not effective, not tolerated, or would not offer adequate pain management.32 Extended-release and long-acting opioids drugs should not be used on an as needed basis.
Certain drugs are only appropriate for opioid-tolerant patients. An opioid-tolerant patient is defined as someone who has taken 60 mg daily of oral morphine, 30 mg daily of oral oxycodone, or equianalgesic dosages of other opioids for at minimum one week.32
There is not enough evidence to determine if taking immediate-release opioids for breakthrough pain when using ER/LA opioids is safe outside of palliative care, end of life care, and active cancer.32
The use of abuse-deterrent technologies makes it more difficult and less rewarding to manipulate the opioids. While they still can be abused, it is more challenging to do so. The abuse-deterrent technology does not prevent unintentional overdose, and the document from the Center for Disease Control does not make recommendations regarding abuse-deterrent formulations.
Research suggests Methadone having the highest number of overdose deaths when compared to other opioids when prescribed for chronic pain. Methadone also has cardiac complications such as QT prolongation and cardiac arrhythmias. Also, methadone has a variable and long half-life, which can complicate when peak respiratory depression occurs. There is more interindividual variability in the pharmacodynamics of methadone when compared to other opioids. Methadone should only be used by prescribers that are very familiar with the unique pharmacodynamics and are willing to monitor patients on it carefully.
The pharmacodynamics of transdermal fentanyl is also complicated. A gradual increase in serum concentration can occur over the first 72 hours.32 Absorption can be variable based on factors such as external heat.
Initiation of Opioid treatment should not occur with ER/LA dosing, and this type of drug should not be used for intermittent use. They should be considered only in those who have severe pain and have used intermediate release opioids daily for at least seven days.
Recommendation five suggests that when starting opiates, the lowest effective dosage should take precedence. Extreme caution should be used when prescribing opiates. The risks versus benefits should be reevaluated with dosages above 50 morphine milligram equivalents (MME)/day used.32 If dosages above 90 MME/day used careful documentation of its justification should be accomplished.
Benefits of high dose opioids are not well established, and higher doses are associated with more harm, such as opioid use disorder, overdose, and motor vehicle accidents. While lower doses of opiates reduce the risk, there is no dose threshold eliminating the risk of overdose. Dosage above 90 MME/day is linked to a high risk of overdose with lower dosages associated with less risk.32 According to the CDC document, when dosages pushed to over 50 MME/day, the risk of overdose increases without improving pain control or functional benefit.
When increasing the dosages of opioids, the increase should occur in the smallest amount possible to reduce the risk of overdose. There is no firm evidence on how long to wait before increasing dosages, but waiting for at least five half-lives before increasing the dosage has been recommended. Also, extreme caution should be used in individuals over the age of 65 or those with kidney or liver insufficiency.
When dosages are increased above 50 MME/day, the prescriber should32:
- Assess if the opiate is helping to meet the treatment goals
- Increase the frequency of follow-ups
- Consider providing naloxone
- Provide overdose education
Even patients who have been on high doses for many years, the offer to wean their dosage should occur. The patient should have education regarding recent clinical evidence suggesting that patients on high doses of opiates are at higher risk for overdose, and the provider should offer the patient an opportunity to wean dosage slowly if indicated.
Recommendation six suggests that when using an opioid for acute pain, the provider should use the lowest dose of immediate-release opioids and provide a quantity that is no more than the expected duration that the patient needs. Three days or less is often enough, and more than seven days rarely indicated.
Some research suggests that for back pain managed in a primary care setting, the use of opioid drugs results in a large reduction in pain until the fourth day of treatment, and after that, smaller pain reductions are noted. Opioids should not be prescribed “just in case.32”
Recommendation number seven suggests that patients using opioids for chronic pain should have the benefits and harms evaluated within one to four weeks of beginning therapy or when there is a dose increase. After that, the benefits and harms should be evaluated at least every three months. If benefits do not outweigh the harms, the provider should consider tapering opioids to a lower dosage or discontinuing opioids.
Individuals who continue opioid therapy for three months or more are at increased risk of developing opioid use disorder.32 Therefore, frequent follow-up in the first three months may help reduce the risk of opioid use disorder. Another argument for close follow-up is that the risk of overdose is high during the first two weeks of treatment with ER/LA opioid use. The risk is especially high with methadone or fentanyl.
Research suggests that individuals who do not have pain relief from opioids at one month will likely not have pain relief at six months. Therefore, assessment within the first month is important to determine who will likely benefit from opioid therapy. Frequent assessments should reduce the risk of complications of long-term opioid use such as overdose, opioid use disorder, and other injuries.
Specific individuals are at higher risk for opioid use disorder or overdose, and this includes individuals with a history of a substance use disorder, individuals with depression or another mental health condition, patients taking greater than 50 MME/day, those with a history of overdose, and those taking other central nervous system depressant drugs.32These individuals should be evaluated more frequently. If found to be without benefit from the opiate, strong consideration should occur in reducing the dose or discontinuing the opiate.
When tapering opioids, the dose should be reduced weekly by 10-50%. In individuals who had a severe adverse event, such as an overdose, rapid discontinuation of 2-3 weeks could be utilized.32 For individuals who have utilized opioids for extended periods, reducing dosages slowly may be appropriate. Reducing as slowly as 10% a month may be utilized in individuals who have been taking opioids for years.
A slow reduction in opioid doses reduces the signs of opioid withdrawal such as anxiety, nausea, vomiting, diarrhea, tremor, increased heart rate, insomnia, drug craving, and abdominal pain.
Recommendation number eight suggests that risk factors for opioid-related harms should be assessed before starting therapy and during opioid therapy. Also, clinicians should implement strategies to reduce risk in individuals at high risk. The strategies would include individuals on greater than 50 MME per day, those with a history of an overdose, a history of a substance use disorder, or those on concurrent benzodiazepines.
One strategy to reduce the risk of overdose death includes prescribing naloxone. Naloxone can reverse the opioid when there is severe respiratory depression. Naloxone has the potential to bring on acute withdrawal symptoms in patients who are physically dependent on opioids.
Other factors that place patients at high risk for overdose including those with sleep-related breathing disorders such as sleep apnea or congestive heart failure, pregnancy, mental health issues, those with renal or liver insufficiency, and those greater than age 65.32
Pregnancy puts both mother and fetus at risk because it can increase the risk of poor fetal growth, congenital disabilities, stillbirth, and preterm delivery. It can also lead to neonatal opioid withdrawal. When prescribing opioids for anyone of childbearing age, it is essential to discuss a possible consequence of opioids during pregnancy.
Prescribing drugs, including opioids, can be challenging in older adults. Some of the concerns include reduced renal or hepatic function, higher risk of respiratory depression, increased risk of side effects including cognitive impairment, more comorbid medical problems, polypharmacy, higher risk of falls, and constipation.
Extra caution should be utilized in individuals with mental health problems when prescribing opioids.32 This group of individuals is at higher risk for opioid use disorder and increased risk for drug overdose (especially in those with depression). For individuals with significant psychiatric instability or high suicide risk, opioid therapy should not be initiated. Also, individuals who have been prescribed benzodiazepines should very cautiously be prescribed opiates, if at all.
The patient should be asked about drug and alcohol use. Also, the prescriber should use the prescription drug monitoring program (PDMP) database before prescribing. For individuals with a substance use disorder obtaining outside consultation with a substance use disorder specialist or pain specialist regarding the management of pain is recommended.
Recommendation number nine suggests that the clinician should review the PDMP database to determine previous/current opioid prescriptions as well as other drugs that may interact and place the patient at higher risk for overdose.32 The clinician should review this data at a minimum of every three months, but as often as every prescription is written.
Research is limited on the benefits of PDMPs. However, evidence suggests that individuals who received opioid prescriptions from multiple prescribers and at high doses are at the highest risk for overdose. The PDMP can help detect these situations.
Providers should not dismiss patients from their practice based on data received from these databases. Doing so has the potential to have adverse health outcomes. The PDMP provides the provider and opportunity to intervene to reduce the risk of overdose by providing interventions as providing education, considering alternative therapies, or prescribing naloxone.
Recommendation number ten suggests that when prescribing opioids for chronic pain, the use of urine drug testing should be used before the start of therapy, and at least once a year. The use of urine drug testing will ensure the patient is taking the drugs as prescribed and that there are no illicit drugs in the patient’s system.32
The use of other controlled substances increases the risk of overdose. Urine drug testing has the potential to identify these patients and reduce risk. Urine drug testing also can determine when patients are not utilizing prescriptions as prescribed, which may point to diversion or side effects that limit compliance.
While urine drug testing should be done before starting opioid therapy, there is disagreement with how frequently testing should be done during long-term therapy. It should be done at least once a year. In high-risk individuals, more frequent testing should ensue.
Patients should have educated regarding the purpose of drug testing – to improve patient safety. Before testing, the provider should ask about the use of other drugs and if there might be any unexpected results. The clinician should be prepared for any unanticipated results and should have a plan for dealing with them. Unexpected results should be discussed with the patient to determine if there is a logical explanation. If the unexpected results (for example, negative for a prescribed drug or positive for an unexpected drug) are not explained, then confirmatory testing should occur.
Confirmed unexpected results can lead to one of the following outcomes32:
- Modification of the pain management strategy
- More frequent evaluations
- Tapering/stopping the opioids. When testing for expected drugs is repeatedly negative, then abrupt discontinuation is appropriate (as the patient is not taking the drug)
- More frequent re-evaluation
- Giving naloxone
- Referral for substance use disorder treatment
Clinicians should not remove the patient from care due to an unexpected urine drug test. The abrupt removal from treatment is a safety measure as the patient could have withdrawal or obtain drugs from another source or even start heroin. It could also be construed as patient abandonment. Lastly, it may miss a chance to get the patient into treatment for substance abuse disorder.
Recommendation eleven suggests avoiding prescribing an opioid and benzodiazepine together. This combination reduces respiratory drive and significantly increases the risk of overdose. The recommendation is not an ultimatum to never prescribe these two agents together but should be done rarely and with extreme consideration.32
For example, a patient who has been on a long-term, low dose benzodiazepine and develops severe acute pain may be a candidate for a low dose opiate drug.
Other drugs that suppress the central nervous system should be avoided in those on opiates. These may include sedatives, hypnotics, muscle relaxants, some antidepressants, and sedating antihistamines.
Recommendation number twelve recommends using an evidence-based treatment in those with opioid use disorder, which may include drug-assisted treatment (MAT) with behavioral therapy.
Points discussed under this recommendation include32:
- Opioid dependence is estimated to be present in between 3-26% of primary care patients on opioids for chronic pain. The use of MAT is effective in preventing relapse in those with opioid use disorder.32
- MAT can occur with buprenorphine or methadone and, in some cases, naltrexone. Naltrexone blocks opioids effects and can be given as daily oral therapy or as monthly injections.
- Providers should be aware of community resources available to help patients get treatment for opioid use disorder.
- The use of MAT in pregnant women with opioid use disorder improves maternal outcomes. Treatment should be with buprenorphine or methadone, not naltrexone.
The CDC guideline aims to enhance the communication between patient and provider regarding the risks and benefits of opioid treatment in chronic pain. It also looks to reduce the risks of long-term opioid therapy and improve effectiveness and safety.