This document outlines key recommendations for clinicians on prescribing opioids for chronic pain, aiming to balance effective pain management with minimizing risks associated with opioid use. These guidelines emphasize nonpharmacologic and nonopioid therapies as first-line treatments, and provide detailed advice on opioid selection, dosage, duration, risk assessment, and discontinuation. It is crucial for healthcare providers to understand and implement these recommendations to ensure patient safety and optimize treatment outcomes.
I. Determining When to Initiate or Continue Opioids for Chronic Pain
1. Prioritizing Nonpharmacologic and Nonopioid Therapies (Category A, Evidence Type 3)
For chronic pain management, nonpharmacologic and nonopioid pharmacologic therapies are strongly recommended. Opioid therapy should only be considered if the anticipated benefits for both pain reduction and functional improvement are expected to outweigh the significant risks to the patient. If opioids are deemed necessary, they must be used in conjunction with nonpharmacologic and nonopioid pharmacologic approaches whenever appropriate.
Rationale: A comprehensive review of evidence indicates that numerous nonpharmacologic treatments, such as physical therapy, psychological therapies like Cognitive Behavioral Therapy (CBT), and specific interventional procedures, can effectively manage chronic pain. Exercise therapy, a cornerstone of physical therapy, has demonstrated high-quality evidence of reducing pain and improving function in osteoarthritis of the hip and knee, with sustained benefits lasting for several months. Multimodal and multidisciplinary rehabilitation programs, combining psychological and physical therapies, have proven more effective in reducing long-term pain and disability compared to standard care or physical treatments alone.
Several nonopioid medications, including acetaminophen, NSAIDs, antidepressants, and anticonvulsants, offer effective pain relief for chronic conditions. Acetaminophen and NSAIDs are particularly useful for arthritis and low back pain. Anticonvulsants like pregabalin and gabapentin are effective for neuropathic pain conditions such as diabetic neuropathy and post-herpetic neuralgia. Tricyclic antidepressants and SNRIs provide analgesia for neuropathic pain and fibromyalgia, often at lower doses than used for depression treatment, and can be particularly beneficial for patients with co-existing pain and depression.
While opioids can provide short-term pain relief, there is limited evidence of sustained long-term benefit in pain, function, or quality of life. Conversely, long-term opioid use carries significant risks, including opioid use disorder, overdose, myocardial infarction, and motor vehicle accidents. Integrated pain management, involving medical, psychological, and social aspects of care, is essential. Nonpharmacologic approaches like exercise and CBT encourage active patient participation and can lead to lasting improvements without the risks associated with opioids. Despite potential barriers to access and cost, elements of these therapies can be integrated into primary care.
To guide treatment selection, accurate diagnosis is paramount. Evaluation should include a detailed patient history, physical examination, and diagnostic testing when indicated. For complex pain syndromes, specialist consultation may be beneficial. Understanding the underlying pain mechanism, whether neuropathic or nociceptive, informs medication choice. It is important to note that evidence supporting long-term opioid use is limited for conditions like low back pain, headache, and fibromyalgia, where opioids are frequently prescribed. When considering medications, clinicians must weigh benefits against risks, especially concerning falls risk with sedating medications and risks associated with NSAIDs in vulnerable populations. Topical NSAIDs may be preferable to oral NSAIDs in older adults with localized osteoarthritis to minimize systemic effects.
Experts strongly agree that opioids should not be considered first-line or routine therapy for chronic pain outside of active cancer, palliative, and end-of-life care, given their limited long-term benefits and significant potential harms. Nonopioid therapies, while also having limited long-term evidence, present much lower risks. This recommendation does not imply mandatory sequential failure of nonopioid therapies before considering opioids. Instead, a careful risk-benefit assessment within the specific clinical context should guide initial therapy decisions. In certain situations, such as headache or fibromyalgia, the risks of opioids are unlikely to be outweighed by benefits, regardless of prior therapies. Conversely, in cases of serious illness with poor prognosis, or contraindications to other treatments, opioids might be appropriate upfront if patient comfort is the primary goal. When opioids are used, they are most effective when integrated with nonpharmacologic therapies.
2. Establishing Treatment Goals and Discontinuation Plans Before Initiating Opioids (Category A, Evidence Type 4)
Prior to starting opioid therapy for chronic pain, clinicians must establish clear treatment goals with patients, including realistic expectations for pain relief and functional improvement. It is also essential to consider and plan for opioid discontinuation should benefits not outweigh risks. Opioid therapy should only continue if there is clinically significant improvement in both pain and function that justifies the ongoing risks to patient safety.
Rationale: Clinical evidence lacks support for the long-term benefits of opioid therapy for chronic pain and highlights a dose-dependent increase in serious harms. Studies assessing risk assessment tools have yielded inconsistent results. Research focusing on long-term outcomes (≥1 year) comparing opioid use to non-use or placebo reveals that while some patients who continue opioid therapy for at least six months may experience pain relief, evidence for improved function or quality of life is insufficient. This uncertainty underscores the difficulty in predicting individual patient response and necessitates an “exit strategy” if therapy proves ineffective.
Experts concur that before initiating opioid therapy for chronic pain outside of active cancer, palliative, and end-of-life care, clinicians must define effectiveness evaluation and set treatment goals collaboratively with patients. While distinguishing between acute and chronic pain initiation can be challenging, pain lasting beyond 3 months or past normal tissue healing is generally considered chronic. Opioid prescriptions for ≥30 days are likely indicative of long-term therapy initiation or continuation. Therefore, treatment goals should be established before prescribing opioids for this duration, or for new patients already on opioids. Although evidence on written agreements or treatment plans is limited, proactively setting a plan clarifies expectations regarding opioid prescribing, monitoring, and discontinuation criteria (e.g., unmet goals, no longer needed, adverse events), enhancing patient safety.
Treatment goals should encompass improvements in both pain and function, recognizing that function extends beyond physical aspects to include emotional and social dimensions. Validated instruments like the PEG Assessment Scale can track patient outcomes, with a 30% improvement in both pain and function considered clinically meaningful. Monitoring progress towards patient-centered functional goals is also crucial. Clinicians should use these goals to assess therapy benefits against risks at follow-up intervals (see Recommendation 7). Co-existing conditions like depression and anxiety can hinder pain resolution; therefore, validated assessments for these conditions are important (see Recommendation 8), ensuring optimized treatment. If meaningful improvement in pain and function is not achieved, clinicians should consider opioid tapering and discontinuation (see Recommendation 7) and prioritize nonpharmacologic and nonopioid approaches (see Recommendation 1).
3. Discussing Risks and Benefits with Patients Before and During Opioid Therapy (Category A, Evidence Type 3)
Before initiating and periodically during opioid therapy, clinicians must engage in thorough discussions with patients regarding the known risks and realistic benefits of opioid therapy, as well as patient and clinician responsibilities in managing this therapy.
Rationale: Clinical evidence lacks studies evaluating patient education or opioid treatment plans as risk mitigation strategies. However, contextual evidence reveals patient information gaps and missed communication opportunities regarding safety. Given the evidence gaps, uncertain long-term benefits, and potential for serious harms, patient education and pre-therapy discussion are crucial for incorporating patient preferences and values into clinical decisions. Experts agree that key communication elements include realistic benefit expectations, common and serious harms, and responsibilities for risk mitigation.
Patient involvement in decisions regarding opioid therapy is paramount. Clinicians must ensure patients are fully aware of potential benefits, harms, and alternatives before initiating or continuing opioids. Open and honest discussions should facilitate mutual decision-making. Important discussion points include:
- Realistic Benefit Expectations: Emphasize that while opioids can reduce short-term pain, long-term pain or functional improvement evidence is lacking, and complete pain relief is unlikely.
- Function as a Primary Goal: Highlight functional improvement as a key objective, achievable even with persistent pain.
- Serious Adverse Effects: Inform patients about potentially fatal respiratory depression and the risk of developing opioid use disorder, a serious, lifelong condition.
- Common Side Effects: Discuss common effects like constipation, dry mouth, nausea, drowsiness, confusion, tolerance, dependence, and withdrawal symptoms. Advise on hydration, fiber intake, and physical activity to prevent constipation, and consider stool softeners or laxatives.
- Driving Safety: Discuss potential impacts on driving ability, especially at therapy initiation, dose increases, or concurrent use of CNS depressants like benzodiazepines or alcohol.
- Dosage-Related Risks: Explain increased risks of opioid use disorder, respiratory depression, and death at higher doses, emphasizing the importance of adhering to prescribed amounts and frequency.
- Risks of Combining with Other Substances: Review increased respiratory depression risks when combined with benzodiazepines, sedatives, alcohol, heroin, or other opioids.
- Risks to Household Members: Discuss risks of intentional or unintentional sharing, including overdose potential and susceptibility of young children to accidental ingestion. Advise on secure storage and safe disposal of unused opioids.
- Periodic Reassessment: Emphasize the importance of regular reassessment to ensure ongoing benefit, allowing for discontinuation and consideration of alternative treatments if opioids are ineffective or harmful.
- Risk Mitigation Precautions: Discuss planned use of prescription drug monitoring programs (PDMP – see Recommendation 9) and urine drug testing (see Recommendation 10). Consider naloxone discussion for overdose reversal (see Recommendation 8).
- Cognitive Limitations: Assess for cognitive limitations that might interfere with therapy management, especially in older adults, and consider caregiver involvement.
Given the potential for benefit reduction or risk escalation over time, clinicians should periodically review expected benefits and risks of continued opioid therapy with patients, ideally every 3 months (see Recommendation 7).
II. Opioid Selection, Dosage, Duration, Follow-Up, and Discontinuation
4. Prescribing Immediate-Release Opioids Over Extended-Release/Long-Acting (ER/LA) Opioids for Initial Therapy (Category A, Evidence Type 4)
When initiating opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids rather than extended-release/long-acting (ER/LA) formulations.
Rationale: ER/LA opioids, including methadone, transdermal fentanyl, and extended-release versions of oxycodone, oxymorphone, hydrocodone, and morphine, carry a higher risk of overdose compared to immediate-release opioids, particularly at treatment initiation. There is no evidence suggesting ER/LA opioids are more effective or safer than immediate-release opioids or that time-scheduled ER/LA use reduces misuse or addiction risks.
The FDA has modified labeling for ER/LA opioids, recommending their use only for “management of pain severe enough to require daily, around-the-clock, long-term opioid treatment” when alternative options are ineffective or inadequate, and not for “as needed” pain relief. Some ER/LA opioids are only appropriate for opioid-tolerant patients. Time-scheduled ER/LA opioid use can lead to higher total daily dosages compared to intermittent, as-needed immediate-release opioid use. Experts also raise concerns about the safety of using immediate-release opioids for breakthrough pain with ER/LA opioids, potentially leading to dose escalation.
Abuse-deterrent technologies in ER/LA opioids aim to prevent manipulation for non-oral routes of administration but do not prevent abuse through oral intake, the most common route. The “abuse-deterrent” label does not eliminate abuse risk. No studies demonstrate the effectiveness of these technologies as a risk mitigation strategy. Furthermore, they do not prevent unintentional overdose from oral intake.
Methadone and transdermal fentanyl pose unique challenges. Methadone is associated with a disproportionate number of overdose deaths, cardiac arrhythmias, and complex pharmacokinetics and pharmacodynamics. Transdermal fentanyl absorption and pharmacodynamics are complex and influenced by factors like external heat, and mcg/hour dosing can be confusing. These complexities can elevate overdose risk, especially for new users or clinicians unfamiliar with these medications.
Experts agree that ER/LA opioids should not be initiated for opioid-naive patients or prescribed for intermittent use. They should be reserved for severe, continuous pain and considered only for patients already receiving daily immediate-release opioids for at least a week. When transitioning to ER/LA opioids, clinicians should consult product labeling and reduce total daily dosage to account for incomplete opioid cross-tolerance. Caution is advised with ER/LA opioids in patients with renal or hepatic dysfunction due to potential drug accumulation. While combining immediate-release and ER/LA opioids may be necessary during transitions, it is generally preferable to avoid this combination due to increased risk and diminishing returns for chronic pain.
When ER/LA opioids are necessary, those with predictable pharmacokinetics and pharmacodynamics are preferred to minimize unintentional overdose risk. Methadone should not be a first-line ER/LA opioid due to its unique risk profile. Only clinicians familiar with methadone’s risks and prepared for patient education and close monitoring, including QT prolongation risk assessment and ECG monitoring, should consider prescribing it. Similarly, transdermal fentanyl should only be prescribed by clinicians familiar with its dosing and absorption properties and capable of educating patients on its use.
5. Prescribing the Lowest Effective Opioid Dosage (Category A, Evidence Type 3)
Upon initiating opioid therapy, clinicians should prescribe the lowest effective dosage. Caution is advised at any dosage level. Careful reassessment of individual benefits and risks is crucial when considering dosage increases to ≥50 morphine milligram equivalents (MME)/day. Increasing dosage to ≥90 MME/day should be avoided or carefully justified.
Rationale: The benefits of high-dose opioids for chronic pain are not well-established. Evidence supporting dose titration for improved pain control, function, or quality of life is limited. One randomized trial found no significant difference in pain or function between liberal dose escalation and dosage maintenance. Conversely, risks of serious harms associated with opioid therapy escalate with higher dosages, including increased risks of motor vehicle injury, opioid use disorder, and overdose. Opioid overdose risk exhibits a dose-response relationship, significantly increasing at dosages of 50–127 MME/day and rising further at ≥100 MME/day.
When opioids are indicated for chronic pain outside of active cancer, palliative, and end-of-life care, clinicians should initiate therapy at the lowest effective dose, as per product labeling for opioid-naive patients and tolerance guidance for opioid-experienced patients. Extra caution is necessary when initiating opioids in patients aged ≥65 years and those with renal or hepatic insufficiency due to potential drug accumulation. Dosage increases should be implemented cautiously and incrementally, as overdose risk escalates with each increase. While specific dosage titration intervals are not definitively established, waiting at least five half-lives before increasing dosage, and at least a week before increasing methadone dosage, is recommended to ensure full effect evaluation. Patient re-evaluation after dosage increases should assess changes in pain, function, and risk for harm (see Recommendation 7). Before increasing total opioid dosage to ≥50 MME/day, reassess whether opioid treatment is meeting treatment goals (see Recommendation 2). At or above 50 MME/day, implement additional precautions, including more frequent follow-up (see Recommendation 7) and considering naloxone and overdose prevention education (see Recommendation 8). Avoid increasing dosage to ≥90 MME/day unless carefully justified based on individualized risk-benefit assessment, considering diagnosis, incremental benefits vs. harms at higher doses, alternative treatments, and specialist consultation. If improvement is not seen at ≥90 MME/day, or if escalating dosage needs arise, discuss alternative pain management approaches, consider opioid tapering or discontinuation (see Recommendation 7), and consult a pain specialist. Be aware of state-level MME thresholds and associated clinical protocols.
For established patients on high-dose opioids or those transferring from other clinicians, opioid dosage reduction may be anxiety-inducing. Tapering can be particularly challenging after years of high-dose use due to physical and psychological dependence. These patients should be offered the opportunity to re-evaluate high-dose opioid use in light of overdose risk evidence. Clinicians should non-judgmentally explain the increased overdose risk at higher doses and offer to collaborate on tapering to safer dosages. For patients agreeing to taper, a collaborative tapering plan is essential (see Recommendation 7). Slow tapers and pauses may be necessary, especially for long-term, high-dose users. Monitor for anxiety, depression, and opioid use disorder (see Recommendations 8 and 12) during tapering and arrange management for these co-morbidities. For patients tapering or remaining on high doses, establish continued therapy goals (see Recommendation 2), maximize nonpharmacologic and nonopioid treatments (see Recommendation 1), and consider pain specialist consultation.
6. Limiting Opioid Quantity and Duration for Acute Pain (Category A, Evidence Type 4)
Long-term opioid use often originates from 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 is often sufficient; more than seven days is rarely needed.
Rationale: 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 prescribing ≤3 days of opioids in most cases, with some recommending ≤7 days. Physical dependence can develop after a few days of opioid exposure. Limiting prescription duration minimizes the need for tapering to prevent withdrawal symptoms. Each day of unnecessary opioid use increases dependence likelihood without added benefit, and shorter prescriptions reduce pill availability for diversion.
Experts agree that when opioids are necessary for acute pain, clinicians should prescribe the lowest effective dose for the shortest duration needed to minimize unintended long-term use initiation. The lowest effective dose should be determined using product labeling as a starting point, adjusted for pain severity and patient factors like renal or hepatic insufficiency (see Recommendation 8). Based on clinical experience, a ≤3-day opioid supply is often sufficient for most acute pain cases not related to surgery or trauma. For example, studies on acute low back pain show significant pain reduction within four days of treatment. While some acute pain types may require slightly longer treatment (≤3–5 days or ≤3–7 days), a 7-day range may be too long for typical acute pain syndromes seen in primary care.
Acute pain can often be managed without opioids. Thorough patient evaluation is crucial to identify reversible pain causes and underlying etiologies. When opioids are warranted for nontraumatic, nonsurgical acute pain, prescribe no more quantity than needed for the expected duration of severe pain, often 3 days or less, unless clearly justified. More than 7 days is rarely necessary. Post-surgical pain management is outside the scope of these guidelines. Avoid prescribing “just in case” opioids. Re-evaluate patients with prolonged severe acute pain to confirm diagnosis and adjust management. Due to longer half-lives and effects of ER/LA opioids, they should not be used for acute pain treatment.
7. Regular Evaluation of Benefits and Harms of Continued Opioid Therapy (Category A, Evidence Type 4)
Clinicians should evaluate benefits and harms with patients within 1 to 4 weeks of starting opioid therapy for chronic pain or dose escalation. Subsequent evaluations should occur every 3 months or more frequently. If benefits do not outweigh harms, clinicians should optimize other therapies and work with patients to taper to lower dosages or discontinue opioids.
Rationale: While evidence on optimal monitoring intervals is limited, continuing opioid therapy for 3 months significantly increases opioid use disorder risk. Follow-up within 3 months is crucial for early intervention and prevention. ER/LA opioid overdose risk may be particularly high in the first 2 weeks of treatment. Patients without pain relief after 1 month are unlikely to benefit at 6 months. Reassessment within 1 month of initiation provides an opportunity to minimize long-term use risks by discontinuing opioids in patients not experiencing clear benefit. Experts note that overdose risks are highest in the first 3–7 days after initiation or dose increase, especially with methadone or transdermal fentanyl. Follow-up within 3 days is recommended for methadone initiation or increase, and within 1 week for other ER/LA opioids.
Initial follow-up within 1–4 weeks of starting long-term opioid therapy or dose escalation should assess benefits and harms. Shorter intervals are advisable for ER/LA opioid initiation/increase or dosages ≥50 MME/day. Even shorter intervals (within 3 days) should be considered for methadone. Assess function, pain control, and quality of life using tools like the PEG Assessment Scale and/or patient-centered functional goals (see Recommendation 2). Inquire about common adverse effects (see Recommendation 3) and early warning signs of serious issues like overdose (sedation, slurred speech) or opioid use disorder (craving, uncontrolled use). Discuss patient preferences regarding continuation based on benefit-harm balance.
Regular reassessment, at least every 3 months, is essential for all patients on long-term opioid therapy, including new patients already on such therapy. Reassessments should determine if opioids continue to meet treatment goals (pain and function improvement), identify adverse events or warning signs, detect opioid use disorder signs (uncontrolled use, related problems), re-evaluate benefit-risk balance, and consider dosage reduction or discontinuation. Ideally, reassessments should be in-person and conducted by the prescribing clinician. Virtual visits with video and audio may be acceptable in remote areas, with in-person visits at least annually. More frequent reassessments are needed for patients at higher risk (depression, substance use disorder history, overdose history, ≥50 MME/day, concurrent CNS depressants). If sustained improvements are lacking, high-risk regimens are used without benefit, patients desire reduction/discontinuation, or serious adverse events/warning signs occur, work with patients to reduce dosage or discontinue opioids when possible. Maximize nonpharmacologic and nonopioid pain management (see Recommendation 1) and consider pain specialist consultation.
Considerations for Tapering Opioids
While evidence comparing tapering protocols is limited, weekly reductions of 10%–50% of the original dosage have been recommended. Rapid tapers (2–3 weeks) may be necessary after severe adverse events like overdose. Slower tapers (e.g., 10% per month) may be better tolerated, especially for long-term users. Opioid withdrawal during pregnancy is associated with risks.
Tapering should be slow enough to minimize withdrawal symptoms (craving, anxiety, insomnia, abdominal pain, etc.). A 10% weekly dose reduction is a reasonable starting point, with individualized plans. Tapers may need pauses and restarts, and slowing down at lower dosages. Progress is the key indicator of success. Once the lowest available dose is reached, dosing intervals can be extended, and opioids can be stopped when taken less than once daily. More rapid tapers may be needed for safety (e.g., after overdose). Ultrarapid detoxification under anesthesia is dangerous and should be avoided. Expert consultation is needed for tapering during pregnancy. Patients not taking opioids do not require tapers. Discuss increased overdose risk upon return to previous higher doses after tapering. Primary care clinicians should collaborate with mental health and pain specialists for nonopioid pain management and psychosocial support. Detailed tapering guidance and withdrawal management resources are available. If opioid use disorder signs emerge, offer or arrange treatment (see Recommendation 12) and consider naloxone (see Recommendation 8).
III. Assessing Risk and Addressing Harms of Opioid Use
8. Evaluating Risk Factors for Opioid-Related Harms and Offering Naloxone (Category A, Evidence Type 4)
Before starting and periodically during opioid therapy, clinicians should evaluate risk factors for opioid-related harms. Management plans should incorporate risk mitigation strategies, including considering offering naloxone when risk factors like overdose history, substance use disorder history, higher opioid dosages (≥50 MME/day), or concurrent benzodiazepine use are present.
Rationale: Evidence on how opioid harms vary based on patient demographics or comorbidities is limited. However, contextual evidence and expert opinion identify risk factors that increase susceptibility to opioid harms, necessitating additional mitigation strategies. Risk factor assessment should be periodic, with frequency varying based on the factor and patient characteristics (e.g., alcohol use requires more frequent follow-up). Consider naloxone, more frequent re-evaluation (see Recommendation 7), and referrals to pain and/or behavioral health specialists when risk factors 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 patients with mild sleep-disordered breathing. Avoid prescribing opioids to patients with moderate or severe sleep-disordered breathing whenever possible to minimize overdose risks.
Pregnant Women
Opioid use in pregnancy may carry additional risks for both mother and fetus, including stillbirth, poor fetal growth, preterm delivery, and birth defects. Neonatal opioid withdrawal syndrome is a significant concern. Clinicians and patients must carefully weigh risks and benefits when considering opioids for chronic pain during pregnancy. Discuss family planning and potential impacts of long-term opioid use on future pregnancies with reproductive-age women before initiating therapy. Expert consultation is needed when considering tapering opioids in pregnant women due to withdrawal risks. For pregnant women with opioid use disorder, medication-assisted therapy with buprenorphine or methadone is recommended. Delivery at a facility equipped to manage neonatal opioid withdrawal syndrome is advisable. Codeine should be avoided in breastfeeding mothers due to neonatal toxicity risks.
Patients with Renal or Hepatic Insufficiency
Increased caution and monitoring (see Recommendation 7) are essential when prescribing opioids to patients with renal or hepatic insufficiency due to decreased 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 of both nonopioid and opioid therapies. Reduced renal function and medication clearance in older adults increase opioid accumulation risk and narrow the therapeutic window. Cognitive impairment, common in 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. Increased caution and monitoring (see Recommendations 4, 5, and 7) are crucial. Educate older adults about risky medication behaviors and implement interventions to mitigate common opioid risks like constipation and falls.
Patients with Mental Health Conditions
Psychological distress often hinders pain and function improvement. Assess for anxiety, PTSD, and depression using validated instruments. Increased caution and monitoring (see Recommendation 7) are needed due to higher opioid use disorder risk in patients with mental health conditions, and increased overdose risk in those with depression. Opioid therapy should not be initiated during acute psychiatric instability or uncontrolled suicide risk. Behavioral health specialist consultation is recommended for patients with suicide attempt history or psychiatric disorders. Patients with anxiety are more likely to receive benzodiazepines, exacerbating opioid-induced respiratory depression (see Recommendation 11). Optimize treatment for mental health conditions and consider tricyclic or SNRI antidepressants for analgesic and antidepressant effects in patients with depression and chronic pain.
Patients with Substance Use Disorder
Illicit drugs and alcohol are significant contributors to opioid overdose deaths. Risk stratification tools for misuse and abuse have limited accuracy. Always exercise caution when considering opioids for chronic pain outside of active cancer, palliative, and end-of-life care, and do not overestimate tool effectiveness in ruling out risks.
Inquire about drug and alcohol use using screening questions or validated tools like DAST and AUDIT. Utilize PDMP data (see Recommendation 9) and drug testing (see Recommendation 10) to assess for concurrent substance use. Provide counseling on overdose risks when opioids are combined with other substances (see Recommendation 3) and ensure effective substance use disorder treatment (see Recommendation 12).
Patients with substance use disorders are likely at higher risk for opioid use disorder and overdose. If opioid therapy is considered, discuss increased risks, carefully weigh benefit-risk balance, and implement mitigation strategies, including naloxone consideration and increased monitoring (see Recommendation 7). Consult substance use disorder and pain specialists for complex pain management in this population and communicate with substance use disorder treatment providers if opioids are prescribed.
Patients with Prior Nonfatal Overdose
Prior nonfatal overdose substantially increases future overdose risk. If a patient experiences nonfatal overdose, work to reduce opioid dosage and discontinue opioids when possible (see Recommendation 7). If opioid therapy continues, discuss increased overdose risks, carefully weigh benefit-risk, and implement mitigation strategies, including naloxone consideration and increased monitoring (see Recommendation 7).
Offering Naloxone to Patients When Factors That Increase Risk for Opioid-Related Harms Are Present
Naloxone can reverse respiratory depression and save lives. Consider offering naloxone when prescribing opioids to patients at increased overdose risk, including those with overdose history, substance use disorder history, concurrent benzodiazepine use (see Recommendation 11), risk of returning to high doses after periods of abstinence, and those taking higher opioid dosages (≥50 MME/day). Provide education on overdose prevention and naloxone use to patients and household members. Clinic resources for naloxone training and collaborative practice models with pharmacists can facilitate co-prescribing. Resources for naloxone prescribing are available through Prescribe to Prevent.
9. Reviewing Prescription Drug Monitoring Program (PDMP) Data (Category A, Evidence Type 4)
Clinicians should review the patient’s history of controlled substance prescriptions using state PDMP data to identify patients at high overdose risk due to high opioid dosages or dangerous combinations. PDMP data should be reviewed when starting opioid therapy for chronic pain and periodically during therapy, ranging from every prescription to every 3 months.
Rationale: PDMPs are state databases tracking controlled prescription drugs. While evidence on PDMP effectiveness in overdose, addiction, abuse, or misuse outcomes is limited, PDMP data provides information on multiple prescribers and high dosages, both overdose risk factors. PDMP data is also helpful when patient medication history is unavailable or when patients transition care. However, PDMP information can be misused (e.g., patient dismissal), negatively impacting patient safety.
State policies vary regarding PDMP data timeliness and clinician access workload. Delegated access can reduce prescriber workload. PDMPs are useful tools for opioid therapy initiation and long-term management. Expert opinions vary on PDMP review frequency during long-term therapy due to access issues and reporting lag in some states. Most agree on review every 3 months or more frequently. A minority suggests annual review may be reasonable in low-risk cases.
Clinicians should review PDMP data for opioids and other controlled medications to identify high-risk patients. Ideally, PDMP data should be reviewed before every opioid prescription, especially in states with well-functioning PDMPs and accessible policies. As PDMP integration into electronic health records improves, access will become easier. Improved data timeliness enhances PDMP value in risk identification.
If PDMP data reveals high dosages, dangerous combinations, or multiple prescribers, actions to improve patient safety include:
- Discussing PDMP information with the patient to confirm awareness of other prescriptions and address potential inaccuracies in PDMP data.
- Discussing safety concerns, including increased respiratory depression and overdose risk, and considering naloxone (see Recommendation 8).
- Avoiding concurrent prescribing of opioids and benzodiazepines whenever possible. Communicate with other prescribers to coordinate care (see Recommendation 11).
- Calculating total MME/day to assess overdose risk (see Recommendation 5). Discuss safety concerns, consider tapering, and offer naloxone for high dosages.
- Discussing safety concerns with other prescribers after informing the patient and coordinating care.
- Considering substance use disorder and discussing concerns with the patient (see Recommendation 12).
- Considering urine drug testing to assess for diversion if suspecting patients are sharing or selling opioids (see Recommendations 7 and 10).
Experts agree that patient dismissal based on PDMP information is detrimental to patient safety, constitutes patient abandonment, and misses opportunities for providing crucial information and interventions.
10. Considering Urine Drug Testing (Category B, Evidence Type 4)
When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications, other controlled prescription drugs, and illicit drugs.
Rationale: Concurrent use of opioids with other opioids, benzodiazepines, or heroin elevates overdose risk. Urine drug tests can reveal unreported drug use and identify patients not taking prescribed opioids, potentially indicating diversion or other issues. Urine drug tests do not quantify drug dosage. Evidence on urine drug screening effectiveness for risk mitigation is limited. Urine drug testing can provide valuable information about undisclosed drug use but is susceptible to misinterpretation and may be associated with harmful practices (stigmatization, inappropriate care termination). Routine use with standardized policies can reduce stigma. Random testing is impractical in clinical practice. Clinician time is needed for interpretation, confirmation, and communication of results, adding to testing costs.
Experts agree on urine drug testing before opioid initiation and periodically during therapy to assess for prescribed opioids, other controlled substances, and illicit drugs. Opinions differ on whether this recommendation should apply universally or be patient-specific. While pre-initiation testing is agreed upon, frequency during long-term therapy is debated. Most experts recommend at least annual testing for all patients. Some argue this interval may be too long or short depending on the case and should be clinician-discretionary. More frequent testing has been recommended for higher-risk patients, but risk prediction before testing is challenging.
Initial urine drug testing can use inexpensive immunoassay panels for common opioids and illicit drugs. Less common opioids may require specific testing. Confirmatory testing adds significant costs and should be based on the need to detect specific opioids or unexpected results. Clinicians should understand their practice’s urine drug testing panels and result interpretation. For example, “opiates” immunoassay detects morphine, codeine, and heroin but not synthetic or some semisynthetic opioids. Oxycodone immunoassays may detect oxycodone and oxymorphone. Positive results may reflect metabolites, not necessarily the specific drug tested for. Detailed guidance on interpretation, test selection, drug detection times, and metabolism is available. Avoid testing for substances that won’t affect management or have unclear implications. For example, THC test implications may be uncertain. Limit confirmatory testing to situations and substances with clear management implications to reduce costs. Have a plan for responding to unexpected results. Explain to patients that testing aims to improve safety and discuss expected results. Ask patients about drug use and potential unexpected results to facilitate open communication. Discuss unexpected results with the lab/toxicologist and patient. Patient explanations may obviate confirmatory testing. If unexplained, confirmatory testing may be warranted.
Use unexpected results to improve safety (adjust pain management, taper/discontinue opioids, increase monitoring, offer naloxone, refer for substance use disorder treatment). Repeatedly negative tests for prescribed opioids may warrant discontinuation without taper. Avoid patient dismissal based on urine drug test results to prevent patient abandonment and missed opportunities for intervention.
11. Avoiding Concurrent Prescription of Opioid Pain Medication and Benzodiazepines (Category A, Evidence Type 3)
Clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible.
Rationale: Benzodiazepines and opioids both depress the central nervous system and respiratory drive. Concurrent use significantly increases potentially fatal overdose risk. While clinical evidence on benzodiazepine co-prescription risks is limited, contextual evidence from epidemiologic studies shows concurrent benzodiazepine use in a large proportion of opioid-related overdose deaths. Case-cohort studies indicate a near quadrupling of overdose death risk with concurrent benzodiazepine and opioid prescriptions compared to opioids alone. Experts agree that while concurrent prescribing may be appropriate in limited situations (e.g., severe acute pain in a patient on stable, low-dose benzodiazepines), it should be avoided whenever possible. Consider risks of concurrent use with other CNS depressants (muscle relaxants, hypnotics) as well. Check PDMP for concurrent controlled medications (see Recommendation 9) and involve pharmacists and pain specialists in management. Due to higher benzodiazepine withdrawal risks, and because opioid tapering can induce anxiety, tapering opioids first may be safer when both are prescribed. Benzodiazepines should be tapered gradually to avoid withdrawal complications. CBT can improve tapering success. If benzodiazepines are tapered or discontinued, or if patients on opioids need anxiety treatment, offer evidence-based psychotherapies (CBT) and/or nonbenzodiazepine medications for anxiety. Communicate with mental health professionals to discuss patient needs, prioritize goals, weigh risks of concurrent exposure, and coordinate care.
12. Offering or Arranging Evidence-Based Treatment for Opioid Use Disorder (Category A, Evidence Type 2)
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.
Rationale: Opioid use disorder is defined in DSM-5 as a problematic opioid use pattern leading to clinically significant impairment or distress, with at least two defined criteria within a year. Prevalence in primary care chronic pain patients on opioid therapy ranges from 3%–26%. Medication-assisted treatment (MAT) with methadone or buprenorphine is more effective in preventing relapse in opioid use disorder. Behavioral therapies combined with MAT can further reduce misuse, increase retention, and improve compliance post-detoxification. Studies primarily focus on illicit opioid use history, but recent studies show buprenorphine and buprenorphine-naloxone effective for prescription opioid dependence as well. Treatment capacity often does not meet community need, and patient cost can be a barrier to buprenorphine treatment. Naltrexone (oral or long-acting injectable) is also an MAT option for nonpregnant adults, especially motivated individuals. Clinicians prescribing opioids should identify community treatment resources and work towards sufficient practice-level treatment capacity.
If opioid use disorder is suspected, discuss concerns with the patient and assess 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 MAT with buprenorphine or methadone and behavioral therapies. Naltrexone is another option for nonpregnant adults. For pregnant women, MAT with buprenorphine (without naloxone) or methadone is recommended. Consider naloxone for overdose prevention in opioid use disorder patients (see Recommendation 8). For problematic opioid use not meeting opioid use disorder criteria, offer tapering and discontinuation (see Recommendation 7). For patients unable to taper, reassess for opioid use disorder and offer MAT if criteria are met.
Physicians can obtain a SAMHSA waiver to prescribe buprenorphine for opioid use disorder in office-based settings. Consider obtaining this waiver in communities with insufficient treatment capacity. A waiver is not needed to offer naltrexone.
Additional guidance is available on buprenorphine and naltrexone treatment induction, use, and monitoring, and on psychosocial treatment components. Clinicians unable to provide treatment should arrange care from substance use disorder specialists or certified opioid treatment programs. Assist patients in finding providers and ensure follow-up and care coordination. Avoid patient dismissal due to substance use disorder, as it can harm patient safety. Opioid use disorder identification is an opportunity for life-saving intervention. Collaborate with patients on safety and treatment. Patients with co-occurring pain and substance use disorder require ongoing pain management, prioritizing nonpharmacologic and nonopioid treatments (see Recommendation 1) and considering pain specialist consultation.
Resources for treatment arrangement include SAMHSA’s buprenorphine physician locator and Opioid Treatment Program Directory, and SAMHSA’s Provider Clinical Support System for Opioid Therapies and Medication-Assisted Treatment.
