The appropriate and safe use of opioids for chronic pain management is a critical aspect of patient care, particularly within palliative care settings. While “Palliative Care Coding Guidelines 2016” might allude to specific billing and coding practices, it’s essential to understand the clinical guidelines that inform these practices, especially concerning opioid prescriptions. This article delves into the recommendations for opioid prescribing for chronic pain, drawing from authoritative sources to provide a comprehensive overview for healthcare professionals.
Understanding Recommendations for Opioid Use in Chronic Pain
Recommendations regarding opioid use are structured around three core areas to ensure patient safety and effective pain management:
- Initiation and Continuation of Opioids: Determining when opioid therapy is appropriate for chronic pain.
- Opioid Management: Guiding opioid selection, dosage, duration, follow-up, and discontinuation.
- Risk Mitigation: Assessing and addressing potential harms associated with opioid use.
These areas are further broken down into 12 specific recommendations designed to assist clinicians in making informed decisions about opioid therapy. These recommendations are grounded in clinical and contextual evidence, expert opinions, and considerations of benefits, harms, patient values, and resource allocation. It’s important to note that these are guidelines to inform clinical judgment, not rigid rules, and patient-specific circumstances should always be paramount in decision-making.
Category of Recommendations and Evidence Types
The recommendations are categorized using a system (Category A and B) indicating the strength of the recommendation and the evidence supporting it (Type 1, 2, 3, or 4). Category A recommendations suggest that the majority of patients should follow the recommended action, while Category B indicates that different approaches may be suitable for different patients, necessitating shared decision-making between clinicians and patients. Even with lower types of evidence (Type 3 and 4), Category A recommendations can be made when there is broad consensus that the benefits of an action significantly outweigh the harms.
It’s crucial to understand that these guidelines are developed based on a careful evaluation of available evidence, which highlights several key points:
- Limited Long-Term Benefit: Evidence does not demonstrate long-term benefits of opioids for chronic pain in terms of pain reduction and functional improvement compared to non-opioid approaches, especially when examined over a year or more. Most studies assessing opioid efficacy are short-term (≤6 weeks).
- Significant Harms: Extensive evidence points to the potential harms of opioid use, including opioid use disorder, overdose, and increased risk of accidents.
- Effective Alternatives: Considerable evidence supports the benefits of nonpharmacologic and nonopioid pharmacologic treatments for chronic pain, often with fewer associated harms compared to long-term opioid therapy.
These overarching assessments underscore the cautious approach recommended for opioid prescribing in chronic pain management.
Determining When to Initiate or Continue Opioids for Chronic Pain
1. Prioritizing Nonpharmacologic and Nonopioid Therapies: Nonpharmacologic therapy and nonopioid pharmacologic therapy are strongly recommended as the preferred approaches for managing chronic pain. Opioid therapy should only be considered when the anticipated benefits for both pain relief and functional improvement are expected to outweigh the risks for the patient. If opioids are deemed necessary, they should be used in conjunction with nonpharmacologic and nonopioid pharmacologic therapies, as appropriate. (Recommendation Category: A, Evidence Type: 3)
This recommendation emphasizes a multimodal approach to pain management. Nonpharmacologic therapies, such as physical therapy, exercise (especially for conditions like osteoarthritis and low back pain), psychological therapies like Cognitive Behavioral Therapy (CBT), and certain interventional procedures, have demonstrated effectiveness in alleviating chronic pain and improving function. Multimodal and multidisciplinary approaches, combining psychological and physical therapies, can lead to sustained improvements in pain and disability.
Nonopioid pharmacologic options, including acetaminophen, NSAIDs, and specific antidepressants and anticonvulsants, are also effective for various chronic pain conditions. For example, acetaminophen and NSAIDs are beneficial for arthritis and low back pain, while anticonvulsants like pregabalin and gabapentin are effective for neuropathic pain. Tricyclic antidepressants and SNRIs can also provide analgesia for neuropathic pain and fibromyalgia, often at lower doses than used for depression. It is important to note that while nonopioid medications carry fewer risks of substance use disorder and overdose compared to opioids, they are not without risks, especially for certain patient populations (e.g., older adults, pregnant women, and those with specific comorbidities). Clinicians should always review FDA-approved labeling and warnings before initiating any pharmacologic therapy.
Alt text: Box 1 showing recommendation categories for chronic pain management, emphasizing nonpharmacologic and nonopioid therapies as preferred.
While opioids can provide short-term pain relief, their long-term efficacy in improving pain, function, and quality of life for chronic pain is uncertain. Conversely, the risks associated with long-term opioid use, such as opioid use disorder, overdose, and other serious adverse events, are well-documented. Therefore, integrated pain management that coordinates medical, psychological, and social aspects of care is crucial. Encouraging active patient participation through therapies like exercise and CBT can lead to sustainable improvements with fewer risks. Access and cost of these therapies can be barriers, but even low-cost options like community-based exercise programs and integrating CBT principles into primary care can be beneficial.
To personalize treatment, a thorough patient evaluation, including diagnosis and pain mechanism identification (neuropathic or nociceptive), is essential. This helps guide therapy selection, considering disease-specific interventions and symptomatic pain management. For instance, neuropathic pain may respond better to medications like tricyclics or anticonvulsants, while NSAIDs might be used for nociceptive pain exacerbations. It’s critical to weigh medication benefits against risks, considering patient-specific factors like fall risk with sedating medications and cardiovascular or gastrointestinal risks with NSAIDs.
Experts strongly agree that opioids should not be first-line or routine therapy for chronic pain outside of active cancer, palliative, and end-of-life care. The decision to use opioids should involve a careful benefit-risk assessment, considering the specific clinical context. In some cases, like headache or fibromyalgia, the risks of opioids may rarely be justified. In contrast, for patients with serious illness, poor prognosis, or contraindications to other therapies, where comfort is the primary goal, opioids might be appropriate even without prior non-opioid treatments. When opioids are used, they are more effective when integrated with nonpharmacologic therapies to maximize pain reduction and functional improvement.
2. Establishing Treatment Goals and Considering Discontinuation: Before initiating opioid therapy for chronic pain, clinicians should collaborate with patients to establish clear treatment goals, including realistic expectations for pain and function. A plan for opioid discontinuation should be considered from the outset if benefits do not outweigh risks. Opioid therapy should only continue if there is clinically significant improvement in pain and function that outweighs the risks to patient safety. (Recommendation Category: A, Evidence Type: 4)
This recommendation highlights the importance of proactive planning and realistic goal-setting. Given the limited evidence for long-term opioid benefit and the dose-dependent increase in serious harms, it is crucial to set measurable goals and have an “exit strategy” if therapy is not successful. While it can be challenging to distinguish between acute and chronic pain initiation, especially in the early stages, prescribing opioids for 30 days or more is generally considered long-term therapy. Therefore, treatment goals should be established before prescribing opioids for this duration, or when seeing new patients already on long-term opioids. While written agreements or treatment plans were not specifically evaluated in the evidence review, they can improve patient safety by clarifying expectations for opioid management, monitoring, and discontinuation.
Treatment goals should encompass improvements in both pain relief and function, contributing to overall quality of life. Function can include physical, emotional, and social dimensions, and mood significantly interacts with pain and function. Validated instruments like the PEG (Pain, Enjoyment of life, General activity) Assessment Scale can track patient outcomes, with a clinically meaningful improvement defined as a 30% improvement in pain and function scores. Monitoring progress towards patient-centered functional goals (e.g., daily activities, work, social engagement) is also essential. Regularly assessing progress against these goals helps in weighing the benefits against the risks of continued opioid therapy. Co-existing conditions like depression and anxiety can hinder pain resolution; thus, their assessment and optimized treatment are also vital. If meaningful improvements in pain and function are not achieved with opioid therapy, clinicians should consider tapering and discontinuing opioids while focusing on nonpharmacologic and nonopioid pain management approaches.
3. Discussing Risks and Benefits with Patients: Before initiating and periodically during opioid therapy, clinicians must engage in comprehensive discussions with patients about the known risks and realistic benefits of opioid therapy. Patient and clinician responsibilities for managing therapy should also be clearly outlined. (Recommendation Category: A, Evidence Type: 3)
This recommendation emphasizes informed consent and shared decision-making. Many patients lack adequate information about opioids, and effective communication about safety is crucial. Given the evidence gaps, uncertain long-term benefits, and potential for serious harms, pre-therapy patient education is paramount. Essential communication elements include:
- Realistic Benefit Expectations: Opioids can reduce short-term pain but lack evidence for long-term improvement in pain or function, and complete pain relief is unlikely.
- Emphasis on Functional Improvement: Function improvement is a primary goal, achievable even with persistent pain.
- Serious Adverse Effects: Discuss potentially fatal respiratory depression and the risk of developing opioid use disorder.
- Common Side Effects: Inform about constipation, dry mouth, nausea, drowsiness, tolerance, dependence, and withdrawal symptoms. Recommend strategies to manage constipation, such as hydration, fiber, and activity, potentially with stool softeners or laxatives.
- Driving Safety: Advise on potential impairment of vehicle operation, especially at therapy initiation, dose increases, or concurrent use of CNS depressants.
- Dose-Dependent Risks: Explain increased risks of opioid use disorder, respiratory depression, and overdose at higher doses, stressing the importance of adhering to prescribed amounts and frequency.
- Risks of Combined Use: Highlight increased respiratory depression risk with benzodiazepines, sedatives, alcohol, and other opioids or illicit drugs.
- Risks to Others: Discuss risks to household members from intentional or unintentional sharing, including overdose and accidental ingestion by children. Advise on secure storage and safe disposal of unused opioids.
- Periodic Reassessment: Emphasize the importance of regular reassessment to ensure ongoing benefit and allow for discontinuation or alternative treatments if needed.
- Risk Mitigation Strategies: Discuss planned use of prescription drug monitoring programs (PDMPs) and urine drug testing. Consider discussing naloxone for overdose reversal.
- Cognitive Limitations: Assess for cognitive limitations that might hinder therapy management, especially in older adults, and involve caregivers if necessary.
Regularly revisiting these points, at least every three months, is crucial to address potential shifts in the benefit-risk balance over time.
Opioid Selection, Dosage, Duration, Follow-Up, and Discontinuation
4. Immediate-Release Opioids Preferred for Initiation: When initiating opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids rather than extended-release/long-acting (ER/LA) opioids. (Recommendation Category: A, Evidence Type: 4)
ER/LA opioids include methadone, transdermal fentanyl, and extended-release formulations of oxycodone, morphine, and hydrocodone. Evidence indicates a higher overdose risk with ER/LA opioid initiation compared to immediate-release opioids. There is no evidence that ER/LA opioids are more effective or safer when used continuously, or that they reduce misuse or addiction risks.
Alt text: Box 2 outlining categories and evidence types for recommendations on opioid therapy for chronic pain.
In 2014, the FDA updated ER/LA opioid labeling to emphasize serious risks and recommend their use only for severe pain requiring daily, around-the-clock, long-term opioid treatment, when alternative options are ineffective or inadequate. They are not intended for “as needed” pain relief. Some ER/LA opioids are only appropriate for opioid-tolerant patients (those already receiving substantial opioid doses). Time-scheduled ER/LA opioid use can lead to higher total daily opioid doses compared to intermittent immediate-release opioids. The safety of using immediate-release opioids for breakthrough pain with ER/LA opioids (outside of active cancer, palliative, or end-of-life care) is also uncertain and may contribute to dose escalation.
Abuse-deterrent formulations aim to prevent manipulation and misuse, but they do not eliminate abuse risk, especially via oral ingestion, the most common route of abuse. No evidence supports their effectiveness as a risk mitigation strategy. They also do not prevent unintentional overdose from oral intake. Experts do not currently recommend specific guidance on abuse-deterrent formulations.
Comparing different ER/LA formulations, overdose risk with methadone versus other ER/LA opioids is inconsistent in studies. However, methadone has been linked to a disproportionate number of overdose deaths relative to its prescription frequency. It also carries risks of cardiac arrhythmias and complex pharmacokinetics, including a long and variable half-life, with respiratory depressant effects peaking later and lasting longer than analgesic effects. Transdermal fentanyl also has complex absorption and pharmacodynamics, with variable serum concentrations and absorption influenced by factors like external heat. Dosing in mcg/hour can be confusing. These complexities may increase fatal overdose risk, especially for new users or clinicians unfamiliar with these medications.
For opioid-naïve patients, ER/LA opioids should not be initiated, nor prescribed for intermittent use. They should be reserved for severe, continuous pain and considered only after daily immediate-release opioid use for at least one week. When switching to ER/LA opioids from immediate-release, product labeling should be consulted, and daily dosage reduced to account for incomplete cross-tolerance. Caution is needed with ER/LA opioids in patients with renal or hepatic dysfunction due to potential drug accumulation and prolonged effects. Combining immediate-release and ER/LA opioids should generally be avoided due to increased risk and diminishing returns, although temporary use during transitions might be necessary.
When ER/LA opioids are prescribed, formulations with predictable pharmacokinetics and pharmacodynamics are preferred to minimize overdose risk. Methadone and transdermal fentanyl pose particular challenges for safe prescribing due to their unique characteristics. Methadone should not be a first-line ER/LA opioid choice. Only clinicians familiar with its risk profile, prepared to educate and closely monitor patients (including QT prolongation risk and ECG monitoring), should consider methadone. Similarly, transdermal fentanyl should only be prescribed by clinicians familiar with its dosing and absorption properties and capable of patient education on its use.
5. Prescribing the Lowest Effective Dosage: When initiating opioids, clinicians should prescribe the lowest effective dosage. Caution is advised at any dosage, with careful reassessment of benefits and risks when considering increasing to ≥50 morphine milligram equivalents (MME)/day, and avoiding increases to ≥90 MME/day, or carefully justifying such increases. (Recommendation Category: A, Evidence Type: 3)
The benefits of high-dose opioids for chronic pain are not well-established. One study found no difference in pain or function outcomes between liberal dose escalation and dosage maintenance. Conversely, risks of serious harms increase with higher opioid dosages, including motor vehicle injury, opioid use disorder, and overdose. Overdose risk increases in a dose-response manner, with significantly elevated risks at dosages ≥50 MME/day.
When opioids are used for chronic pain outside of active cancer, palliative, and end-of-life care, initiation should always be at the lowest effective dose, as per product labeling. Increased caution is needed for older adults (≥65 years) and those with renal or hepatic insufficiency due to potential drug accumulation. Dosage increases should be made cautiously and in small increments, as overdose risk escalates with dose increases. While specific titration intervals lack strong evidence, waiting at least five half-lives before increasing dosage and at least a week for methadone is recommended to assess the full effect of the current dose. Patients should be re-evaluated for pain, function, and harm risk after dosage increases. Before increasing to ≥50 MME/day, reassess treatment goal attainment. If ≥50 MME/day is reached, implement additional precautions: more frequent follow-up and considering naloxone and overdose prevention education for patients and household members. Avoid increasing to ≥90 MME/day, or justify carefully based on individualized benefit-risk assessment, diagnosis, incremental benefit vs. harm at higher doses, other treatments, and pain specialist consultation. If no improvement at ≥90 MME/day, or escalating dosage needs arise, discuss alternative pain management, consider opioid tapering/discontinuation, and consult a pain specialist. Be aware of state-level MME thresholds and associated protocols.
For established patients on high doses, or those transferring care, opioid dose reduction may be anxiety-provoking. However, they should be offered re-evaluation of high-dose opioid use in light of overdose risk evidence. Explain the increased overdose risk at higher doses (≥90 MME/day) non-judgmentally. Empathically review benefits and risks of continued high-dose therapy and offer to collaborate on tapering to safer doses. For patients agreeing to taper, create a collaborative tapering plan. Slow tapers and pauses may be needed, especially after years of high-dose use. Monitor for anxiety, depression, and opioid use disorder during tapering, and manage comorbidities. For those tapering or remaining on high doses, establish treatment goals, maximize nonpharmacologic and nonopioid pain management, and consider pain specialist consultation.
6. Acute Pain Management and Limiting Opioid Duration: Long-term opioid use often begins with acute pain treatment. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and limit the quantity to the expected duration of pain severe enough to require opioids. Three days or less will often suffice; more than seven days is rarely needed. (Recommendation Category: A, Evidence Type: 4)
Opioid use for acute pain is linked to long-term opioid use, and greater initial opioid exposure increases long-term use risk. Guidelines for acute pain management recommend ≤3 days of opioids in most cases, with some recommending ≤7 days. Physical dependence can develop within a few days of opioid exposure, so limiting prescription duration minimizes the need for tapering to prevent withdrawal symptoms. Unnecessary days of opioid use increase dependence likelihood without added benefit and increase pill availability for diversion.
When opioids are needed for acute pain, prescribe the lowest effective dose and for the shortest duration necessary. Use product labeling as a starting point for dosing, adjusting for pain severity and patient factors like renal or hepatic insufficiency. For most non-surgical, non-traumatic acute pain, a ≤3-day supply is often sufficient. Some experts suggest a range of ≤3–5 or ≤3–7 days, but a 7-day range may be too long for typical acute pain in primary care.
Acute pain can often be managed without opioids. Evaluate for reversible causes and serious underlying conditions. When opioids are warranted for non-traumatic, non-surgical acute pain, prescribe only the quantity needed for the expected duration of severe pain, often ≤3 days, rarely exceeding 7 days. Post-surgical pain is outside this guideline’s scope. Avoid “just in case” opioid prescriptions. Re-evaluate patients with prolonged severe acute pain to confirm diagnosis and adjust management. Do not prescribe ER/LA opioids for acute pain due to their longer half-lives and duration of effects.
7. Regular Benefit and Harm Evaluation and Follow-Up: Clinicians should evaluate benefits and harms with patients within 1 to 4 weeks of starting opioid therapy for chronic pain or dose escalation. Regular evaluations should occur every 3 months or more frequently. If harms outweigh benefits, optimize other therapies and work with patients to taper to lower doses or discontinue opioids. (Recommendation Category: A, Evidence Type: 4)
While evidence on optimal monitoring intervals is limited, continuing opioid therapy for 3 months significantly increases opioid use disorder risk. Follow-up sooner than 3 months may be needed for early intervention. Overdose risk with ER/LA opioids may be highest in the first 2 weeks of treatment. Patients without pain relief at 1 month are unlikely to get relief at 6 months. Reassessment within 1 month of starting opioids allows for early discontinuation if benefit is unclear. Experts recommend follow-up within 1-4 weeks of initiating or escalating long-term opioid therapy. Shorter intervals are advised for ER/LA opioid initiation/increase or dosages ≥50 MME/day. Within 3-day follow-up is suggested for methadone initiation/increase.
At follow-up, assess function, pain control, and quality of life using tools like the PEG scale and patient-centered functional goals. Inquire about common side effects (constipation, drowsiness) and warning signs of serious problems (sedation, slurred speech, craving, uncontrolled use). Discuss patient preferences for continuing opioids based on perceived benefits and harms.
Regularly reassess all long-term opioid therapy patients, including new patients already on opioids, at least every 3 months. Determine if opioids still meet treatment goals (sustained pain and function improvement), assess for adverse events, opioid use disorder signs, benefit-risk balance, and potential for dose reduction or discontinuation. Ideally, reassessments should be in-person by the prescribing clinician. Virtual visits with video and audio can be used in remote areas, with in-person visits at least annually. More frequent reassessment is needed for high-risk patients (depression, substance use disorder history, overdose history, ≥50 MME/day, concurrent CNS depressants). If sustained benefit is lacking, high-risk regimens are used without benefit, patients request reduction/discontinuation, or adverse events/warning signs occur, work with patients to reduce or discontinue opioids. Maximize nonpharmacologic and nonopioid pain management and consider pain specialist consultation.
Considerations for Tapering Opioids
While evidence comparing tapering protocols is limited, 10%-50% weekly dose reductions have been recommended. Rapid tapers (2-3 weeks) are suggested for severe adverse events like overdose. Slower tapers (<10% per week, e.g., 10% per month) may be better tolerated, especially after long-term opioid use. Opioid withdrawal during pregnancy can cause miscarriage and premature labor.
When reducing or discontinuing opioids, use a slow taper to minimize withdrawal symptoms (craving, anxiety, insomnia, abdominal pain, vomiting, diarrhea, diaphoresis, tremor, tachycardia, piloerection). A 10% weekly dose reduction is a reasonable starting point, individualized based on patient goals and concerns. Tapers may need pauses and restarts, and slowing at low doses. Success is defined by progress. Once the smallest dose is reached, extend dosing intervals. Stop opioids when used less than once daily. Faster tapers may be needed for safety (e.g., post-overdose). Ultrarapid detoxification under anesthesia is risky and not recommended. Consult expertise when tapering during pregnancy due to fetal risk. Patients not taking opioids do not need tapers. Discuss increased overdose risk upon returning to previous doses after tapering. Collaborate with mental health providers and specialists for nonopioid pain management and psychosocial support during tapering. More detailed tapering guidance is available elsewhere. If opioid use disorder is suspected, offer treatment and consider naloxone.
Assessing Risk and Addressing Harms of Opioid Use
8. Evaluating Risk Factors and Offering Naloxone: Before starting and periodically during opioid therapy, clinicians should evaluate risk factors for opioid-related harms. Incorporate risk mitigation strategies into the management plan, including considering offering naloxone when risk factors for overdose are present, such as overdose history, substance use disorder history, higher opioid dosages (≥50 MME/day), or concurrent benzodiazepine use. (Recommendation Category: A, Evidence Type: 4)
Evidence on how opioid harms vary with demographics or comorbidities is limited. However, certain risk factors increase susceptibility to opioid harms and warrant risk mitigation strategies. Assess risk factors periodically, with frequency based on the factor and patient characteristics (e.g., more frequent follow-up for fluctuating alcohol use). Consider naloxone, more frequent re-evaluation, and specialist referrals when risk factors like overdose history, substance use disorder, high opioid doses (≥50 MME/day), and concurrent benzodiazepine use are present.
Patients with Sleep-Disordered Breathing, Including Sleep Apnea
Risk factors include congestive heart failure and obesity. Careful monitoring and cautious dose titration are needed if opioids are prescribed for mild sleep-disordered breathing. Avoid opioids in moderate or severe sleep-disordered breathing whenever possible to minimize overdose risk.
Pregnant Women
Opioid use in pregnancy carries risks to both mother and fetus, including stillbirth, poor fetal growth, preterm delivery, and birth defects. Neonatal opioid withdrawal syndrome is a significant concern. Carefully weigh risks and benefits of opioid therapy during pregnancy. Discuss family planning and long-term opioid use effects on future pregnancy with reproductive-age women before starting opioids. For pregnant women already on opioids, consult expertise before tapering due to risks to both mother and fetus from withdrawal. For pregnant women with opioid use disorder, medication-assisted therapy with buprenorphine or methadone improves maternal outcomes and should be offered. Arrange delivery at facilities prepared to manage neonatal opioid withdrawal syndrome. For breastfeeding mothers, avoid codeine if possible, and if used, limit to the lowest dose and a 4-day supply due to neonatal toxicity risks.
Patients with Renal or Hepatic Insufficiency
Use extra caution and increased monitoring for opioid use in patients with renal or hepatic insufficiency due to impaired drug processing and excretion, leading to accumulation and a reduced therapeutic window.
Patients Aged ≥65 Years
Pain management in older adults is challenging due to increased risks from both nonopioid and opioid therapies. Reduced renal function and medication clearance in older adults increase opioid accumulation risk and reduce the therapeutic window. Cognitive impairment in some older adults increases medication error risk and makes opioid-related confusion more dangerous. Older adults are also more likely to have comorbidities and polypharmacy, increasing drug interaction risks (e.g., with benzodiazepines). Use extra caution and increased monitoring when prescribing opioids to older adults. Educate older adults on risky medication behaviors (multiple prescribers, saving unused medications). Implement interventions for common opioid risks in older adults, such as exercise, bowel regimens for constipation, falls risk assessment, and cognitive monitoring.
Patients with Mental Health Conditions
Psychological distress often hinders pain and function improvement. Use validated tools like GAD-7, PHQ-9, or PHQ-4 to assess for anxiety, PTSD, and depression to improve pain treatment outcomes. Use extra caution and increased monitoring for patients with mental health conditions due to increased opioid use disorder and overdose risks (especially with depression). Avoid initiating opioid therapy during acute psychiatric instability or uncontrolled suicide risk. Consider behavioral health specialist consultation for patients with suicide attempt history or psychiatric disorder. Patients with anxiety disorders are more likely to receive benzodiazepines, exacerbating opioid-induced respiratory depression. Optimize treatment for depression and other mental health conditions, consulting behavioral health specialists as needed. Consider tricyclic or SNRI antidepressants for chronic pain in depressed patients for analgesic and antidepressant effects, if not contraindicated.
Patients with Substance Use Disorder
Illicit drugs and alcohol are frequent contributors to opioid overdose deaths. Risk stratification tools for opioid misuse/abuse have insufficient accuracy. Exercise caution when considering opioids for chronic pain outside of active cancer, palliative, and end-of-life care and avoid overestimating risk assessment tool capabilities.
Inquire about patient drug and alcohol use using screening questions or validated tools like DAST and AUDIT. Use PDMP data and drug testing to assess for concurrent substance use. Counsel on increased overdose risks with combined drug or alcohol use. Ensure access to effective substance use disorder treatment.
Patients with drug or alcohol use disorders are at higher risk of opioid use disorder and overdose. If considering opioids for chronic pain in these patients, discuss increased risks, carefully weigh benefit-risk, and implement risk mitigation strategies: consider naloxone and more frequent monitoring. Pain management in patients with substance use disorder is complex; consider substance use disorder and pain specialist consultation. Communicate with patients’ substance use disorder treatment providers if opioids are prescribed.
Patients with Prior Nonfatal Overdose
Prior nonfatal overdose significantly increases future overdose risk. If overdose occurs, work to reduce opioid dosage and discontinue if possible. If continuing opioids for chronic pain in patients with prior overdose, discuss increased risks, carefully weigh benefit-risk, and implement risk mitigation: consider naloxone and more frequent monitoring.
Offering Naloxone to Patients When Factors That Increase Risk for Opioid-Related Harms Are Present
Naloxone reverses respiratory depression and can be life-saving. Community-based naloxone distribution is effective in preventing opioid overdose deaths, and clinical setting provision is likely also effective. While ideally, opioid treatment should be avoided when risk factors are present, naloxone should be considered for patients at increased overdose risk: overdose history, substance use disorder history, concurrent benzodiazepine use, risk of returning to high doses after reduced tolerance (e.g., post-incarceration), and higher opioid dosages (≥50 MME/day). Provide overdose prevention and naloxone use education to patients and household members. Collaborative practice models with pharmacists can facilitate naloxone co-prescribing. Resources for naloxone prescribing are available through Prescribe to Prevent.
9. Utilizing Prescription Drug Monitoring Programs (PDMPs): Clinicians should review patient history of controlled substance prescriptions using PDMP data to identify patients at high overdose risk due to opioid dosages or dangerous combinations. Review PDMP data when starting opioid therapy and periodically during therapy, ranging from every prescription to every 3 months. (Recommendation Category: A, Evidence Type: 4)
PDMPs are state-based databases tracking controlled prescription drugs. Some states mandate PDMP review before each opioid prescription. While evidence on PDMP effectiveness on overdose, addiction, abuse, or misuse outcomes is limited, PDMP data provides information on multiple prescribers and high opioid dosages, both overdose risk factors. PDMP data is also helpful when patient medication history is unavailable or during care transitions. However, PDMP information misuse, such as patient dismissal, can harm patient safety.
PDMP data timeliness and clinician workload for access vary by state, affecting PDMP benefit. Delegate access can reduce prescriber workload. Experts agree PDMPs are useful tools for opioid therapy initiation and long-term therapy. However, frequency of PDMP checks during long-term therapy is debated due to access issues and reporting lag in some states. Most experts recommend PDMP review every 3 months or more frequently. A minority suggests annual review when risk factors are absent, given access burden and limited evidence on optimal review intervals.
Review PDMP data for opioids and other controlled medications to identify high-risk patients due to high opioid dosages or dangerous combinations (e.g., opioids and benzodiazepines). Ideally, review PDMP data before every opioid prescription, especially in states with well-functioning and accessible PDMPs. As PDMP integration into electronic health records improves, access will become easier. Improved data timeliness will enhance PDMP value.
If PDMP data reveals high opioid dosages, dangerous combinations, or multiple prescribers, take actions to improve patient safety:
- Discuss PDMP information with the patient and confirm awareness of additional prescriptions. PDMP data can sometimes be inaccurate.
- Discuss safety concerns, including increased respiratory depression and overdose risk, with patients receiving opioids from multiple prescribers or dangerous combinations, and consider naloxone.
- Avoid concurrent opioid and benzodiazepine prescriptions whenever possible. Communicate with other clinicians managing the patient to coordinate care, prioritize goals, and weigh risks.
- Calculate total MME/day for concurrent opioid prescriptions to assess overdose risk. Discuss safety concerns, consider tapering, and offer naloxone if high dosages are found.
- Discuss safety concerns with other prescribing clinicians, ideally after patient discussion and informing them of care coordination plans.
- Consider substance use disorder and discuss concerns with the patient.
- If suspecting opioid sharing or selling, consider urine drug testing to determine if opioids can be discontinued without withdrawal. Negative tests for prescribed opioids may indicate non-adherence, but consider other reasons for negative results.
Experts agree that patient dismissal based on PDMP information is harmful, represents patient abandonment, and misses opportunities for life-saving information and interventions (safer prescriptions, nonopioid pain treatment, naloxone, substance use disorder treatment).
10. Considering Urine Drug Testing: When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy and consider annual urine drug testing to assess for prescribed medications, other controlled prescription drugs, and illicit drugs. (Recommendation Category: B, Evidence Type: 4)
Concurrent use of opioids with other opioids, benzodiazepines, or heroin increases overdose risk. Urine drug tests can detect unreported drug use and identify patients not taking prescribed opioids, potentially indicating diversion or other issues. Urine drug tests do not quantify drug amounts or doses. Evidence on urine drug screening effectiveness for risk mitigation is limited. Urine drug testing can provide useful information about unreported drug use. However, results can be misinterpreted and lead to harmful practices (stigmatization, inappropriate care termination). Routine urine drug testing with standardized policies may reduce stigma. Random testing is impractical in clinical practice, though some clinics randomly send specimens for testing. Urine drug testing costs, often not fully covered by insurance, and clinician time for result interpretation are burdens.
Experts agree urine drug testing should be used before starting opioids for chronic pain and periodically during therapy to assess for prescribed opioids, other controlled substances, and illicit drugs (non-prescribed opioids, benzodiazepines, heroin) that increase overdose risk when combined with opioids. Expert opinion varied on whether this should apply to all patients or be individually decided based on patient values, preferences, and clinical situations. While pre-opioid initiation urine drug testing was agreed upon, frequency during long-term therapy was debated. Most experts recommended annual urine drug testing for all patients as reasonable. Some felt this interval could be too long or short depending on the case and should be at clinician discretion. Previous guidelines recommended more frequent testing for high-risk patients, but predicting risk before testing is challenging, and current tools cannot reliably identify low-risk patients.
Initial urine drug testing can use inexpensive immunoassay panels for common opioids and illicit drugs. Less common opioids may require specific testing. Confirmatory testing increases costs and should be based on need to detect specific opioids not identified by immunoassays or unexpected results. Clinicians should understand the drugs included in their practice’s testing panels and how to interpret results. For example, “opiates” immunoassay detects morphine, codeine, and heroin, but not synthetic opioids (fentanyl, methadone) and may not detect semi-synthetic opioids (oxycodone). However, many labs use oxycodone immunoassays that detect oxycodone and oxymorphone. Positive results may reflect metabolites of prescribed opioids, not necessarily the specific opioid tested for (e.g., hydromorphone from hydrocodone, oxymorphone from oxycodone). Detailed urine drug test interpretation guidance is available elsewhere. Avoid testing for substances that won’t affect patient management or have unclear implications. For example, THC clinical implications may be uncertain. Limit confirmatory testing to substances that can reasonably affect patient management to reduce costs. Before ordering urine drug testing, have a plan for responding to unexpected results. Explain to patients that urine drug testing is for safety improvement and explain expected results (prescribed medication presence, absence of unreported drugs). Ask patients about prescribed and other drug use and potential unexpected results. This allows patients to disclose changes in drug use. Discuss unexpected results with the lab/toxicologist and patient. Patient discussion before confirmatory testing may provide explanations and obviate confirmatory testing needs. For example, a patient might explain opioid discontinuation due to lack of benefit. If unexpected results are unexplained, confirmatory testing (e.g., chromatography/mass spectrometry) may be warranted.
Use unexpected results to improve patient safety (adjust pain management, taper/discontinue opioids, more frequent re-evaluation, naloxone, substance use disorder referral). Repeatedly negative tests for prescribed opioids, confirming non-adherence, allow for prescription discontinuation without tapering. Do not dismiss patients based on urine drug test results, as this is patient abandonment and misses opportunities for safety interventions and substance use disorder treatment.
11. Avoiding Concurrent Prescription of Opioids and Benzodiazepines: Clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible. (Recommendation Category: A, Evidence Type: 3)
Benzodiazepines and opioids both cause central nervous system depression and can decrease respiratory drive. Concurrent use significantly increases fatal overdose risk. While evidence on benzodiazepine co-prescription risks with opioids is limited, epidemiologic data shows concurrent benzodiazepine use in many opioid-related overdose deaths. A study found concurrent benzodiazepine and opioid prescription nearly quadrupled overdose death risk compared to opioid prescription alone. Experts agree that while there may be situations where opioids are appropriate for patients on benzodiazepines (e.g., severe acute pain in a patient on stable low-dose benzodiazepines), concurrent prescribing should be avoided whenever possible. Consider risks of concurrent use of other CNS depressants (muscle relaxants, hypnotics) with opioids. Check PDMP for concurrent controlled medications and consider pharmacist and pain specialist involvement when co-prescribing CNS depressants. Due to higher benzodiazepine withdrawal risks compared to opioids, and anxiety associated with opioid tapering, it may be safer to taper opioids first when both are prescribed and tapering is needed to reduce fatal respiratory depression risk. Taper benzodiazepines gradually because abrupt withdrawal can cause rebound anxiety, hallucinations, seizures, delirium tremens, and rarely, death. A common tapering schedule is a 25% dose reduction every 1-2 weeks. CBT improves tapering success and can be helpful for benzodiazepine taper struggles. If benzodiazepines are tapered/discontinued for anxiety, offer evidence-based psychotherapies (CBT) and/or nonbenzodiazepine anxiety medications. Communicate with mental health professionals managing the patient to coordinate care, prioritize goals, and weigh risks of concurrent benzodiazepine and opioid exposure.
12. Offering Evidence-Based Treatment for Opioid Use Disorder: Clinicians should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone combined with behavioral therapies) for patients with opioid use disorder. (Recommendation Category: A, Evidence Type: 2)
Opioid use disorder (DSM-5 criteria) is a problematic pattern of opioid use causing significant impairment or distress. Prevalence in primary care patients on opioid therapy ranges from 3%–26%. Opioid agonist/partial agonist treatment (methadone maintenance therapy or buprenorphine) is more effective in preventing relapse in opioid use disorder. Behavioral therapies combined with these treatments may reduce misuse, improve retention, and enhance compliance post-detoxification. Studies primarily evaluated illicit opioid users, but recent studies show buprenorphine and buprenorphine-naloxone effective for prescription opioid dependence. Treatment needs often exceed capacity, and patient cost can be a buprenorphine treatment barrier due to limited insurance coverage. Oral or long-acting injectable naltrexone can also be used for opioid use disorder treatment in nonpregnant adults, particularly for highly motivated individuals. Clinicians prescribing opioids should identify community treatment resources for opioid use disorder and work to ensure adequate treatment capacity at the practice level.
If opioid use disorder is suspected, discuss concerns with the patient and assess for opioid use disorder using DSM-5 criteria or refer to a substance use disorder specialist. Offer or arrange evidence-based treatment for patients meeting opioid use disorder criteria, typically medication-assisted treatment (buprenorphine or methadone) with behavioral therapies. Oral or long-acting injectable naltrexone can also be used in nonpregnant adults. For pregnant women with opioid use disorder, medication-assisted therapy with buprenorphine (without naloxone) or methadone improves maternal outcomes and should be offered. Consider naloxone for overdose prevention in patients with opioid use disorder. For problematic opioid use not meeting opioid use disorder criteria, offer opioid tapering/discontinuation. For patients unable to taper, reassess for opioid use disorder and offer opioid agonist therapy if criteria are met.
Physicians can obtain a SAMHSA waiver to prescribe buprenorphine for opioid use disorder treatment in office-based settings. Physicians prescribing opioids in communities with insufficient treatment capacity should strongly consider obtaining this waiver. Naltrexone can be offered without a waiver.
Additional guidance is available on buprenorphine and naltrexone treatment, and effective psychosocial treatments for opioid use disorder. Clinicians unable to provide treatment should arrange for care from substance use disorder specialists, office-based buprenorphine/naltrexone providers, or SAMHSA-certified opioid treatment programs. Assist patients in finding qualified providers and arrange follow-up and care coordination. Do not dismiss patients due to substance use disorder, as this harms patient safety. Opioid use disorder identification is an opportunity for life-saving interventions. Collaborate with patients to increase treatment success likelihood. While opioid use disorder alters opioid therapy benefit-risk, patients with co-occurring pain and substance use disorder need ongoing pain management maximizing benefits relative to risks. Continue nonpharmacologic and nonopioid pain treatments and consider pain specialist consultation for optimal pain management.
Resources for treatment arrangement include SAMHSA’s buprenorphine physician locator, Opioid Treatment Program Directory, Provider Clinical Support System for Opioid Therapies, and Provider’s Clinical Support System for Medication-Assisted Treatment.
