Opioid Management for Chronic Pain

Disease/Disorder

Opioids are essential in the treatment of acute pain and cancer pain, but their role in treating chronic non-cancer pain poses a significant risk to the individual and society in the form of addiction, misuse, and even death if not used appropriately. Evidence supporting the long-term use of opioids for the treatment of chronic noncancer pain is sparse, but it does appear that some carefully selected patients may indeed benefit from this treatment.¹ Therefore, large organizations such as the Centers for Disease Control (CDC) and the American Society of Interventional Pain Physicians have implemented clinical practice guidelines in the last 5 years to help clinicians prescribe opioids effectively and safely in select populations.

Definitions²

• Opioids refer to natural or synthetic substances that act on opioid receptors; “opiates” are a subclass containing alkaloid components found naturally in opium poppy (e.g., morphine).
• Narcotics refer to any substances federally regulated by the Drug Enforcement Agency (DEA).
• Opioid use disorder, which includes dependence and addiction, is defined as the inability to reduce or control drug use, coupled with continued use despite harm, social problems, and failure to fulfill major role obligations at work, school, or home^.
• Pseudoaddiction refers to drug-seeking behavior by patients who have severe pain and includes taking medications in more significant amounts than prescribed, running out early, and the presence of withdrawal symptoms. These behaviors may not be associated with true addiction but rather with under-treatment. These behaviors are usually eliminated after proper medication adjustments are made.
• Tolerance refers to adaptation in which exposure to a drug induces changes that result in diminished drug effects over time.
• Dependence is manifested by a drug class-specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.
• Abuse is the use of an illicit drug or the intentional self-administration of medication for nonmedical purposes, such as to become euphoric or “high.”
• Diversion is the use of a legitimately prescribed medication for illicit purposes, perhaps with the intent to sell or distribute. Examples include stolen, altered, or forged prescriptions or trading for profit on medications.

Etiology

Chronic pain is defined as pain lasting over three months or longer than expected tissue healing. Opioid use in the short term has been shown to improve function and reduce neuropathic and nociceptive non-cancer pain.² Long-term functional improvement studies are lacking, with a 2018 meta-analysis of randomized controlled trials showing statistically significant, but only small, clinical improvements in pain and function, reinforcing the need to tailor therapy to individual patients based on risks and potential benefits.³ Prescribing physicians must find a balance between the appropriate use of opioids to reduce pain and improve function while assessing the risks of developing opioid use disorder, overdose, and drug diversion. From 1999-2021, nearly 645,000 people died from an overdose involving any opioid, including prescription and illicit opioids.⁴ Over 75% of the 107,000 drug overdose deaths in 2021 involved an opioid.⁴ 

The United States suffered a triple-wave epidemic of overdose deaths related to opioids starting in the 1990s.⁵ The first wave began in the 1990s-2010 with the increase in prescribing opioids related to pharmaceutical initiatives on oversupplying the market. The second opioid wave started in 2010 with the rapid increases in heroin-related deaths transitioning to heroin from opioid pills. The third opioid wave began in 2017-2023 with synthetic opioids and the illicit manufacturing of fentanyl.⁵

Epidemiology, including risk factors and primary prevention

Chronic pain is associated with reduced quality of life, increased medical expenditures, and significant economic costs. With respect to the prevalence of chronic pain, in the 2019 National Health Interview Survey, approximately 50.2 million adults in the United States (20.5%) reported pain on most days or a daily basis.⁶ Thus, there is a significant need to manage this population to reduce disease and economic burden. Treatment of chronic pain with opioid medication is associated with its own risks, with the most substantial being death due to overdose from respiratory depression. Risk factors for chronic pain involve socio-demographic, psychological, clinical, and biological factors. Modifiable factors associated with increased risk of chronic pain are smoking, alcohol, lack of physical activity, obesity, and nutrition high in processed foods or sugars.⁷ Non-modifiable risk factors are history of violent injury/abuse, genetics, sleep disorders, younger age, psychiatric disorders, manual occupations, and unemployment.⁷

Primary prevention is mainly dependent on shared education between prescribers and patients. This collaborative approach creates a foundation for establishing the objectives of opioid therapy for pain relief and improvement in function and developing an individualized care plan for the patient based on benefit-risk assessment.⁸ It is essential for providers to inform patients about the potential consequences of long-term opioid therapy that include tolerance, dependence, addiction, immunosuppression, and even death. Other primary prevention methods involve cautious initiation of opioid therapy at the lowest effective dose and limiting the overall duration of treatment. Overall, chronic pain management using opioid medications requires a strong foundation of education and open communication between patients and providers. This collaborative approach is vital to minimize adverse effects, enhance patient satisfaction, and decrease disease burden.

Patho-anatomy/physiology

Opioid receptors are members of a larger superfamily of receptors with seven transmembrane alpha helices coupled with G proteins; G proteins rapidly undergo desensitization and internalization after exposure to an endogenous or exogenous opioid molecule.

The three major types of opioid receptors^9,10

• mu (endorphin): these are most commonly used in clinical practice
• delta (enkephalin)
• kappa (dynorphin)

Mu receptors are found primarily in the brainstem, limbic system, and medial thalamus and are responsible for supraspinal analgesia. Mu1 receptors are related to analgesia and euphoria, while Mu2 receptors are linked to respiratory depression, pruritus, prolactin release, and dependence.⁹ The analgesic effect of opioids is primarily the result of their binding of mu receptors, but binding also occurs at delta and kappa receptions with differing physiological effects. Kappa receptors are found predominately in the spinal cord and have a large role in spinal analgesia, respiratory depression, and dysphoria. The third primary opioid receptor is the delta receptor, which plays a role in analgesia related to peripheral pain and reduction in gastric motility.

Opioid receptors located on the presynaptic terminals of the nociceptive C-fibers and A-delta fibers will activate once bound by an endogenous or exogenous opioid molecule. When activated by an opioid agonist, this will indirectly inhibit voltage-dependent calcium channels and block the release of pain neurotransmitters such as glutamate, substance P, and calcitonin gene-related peptide from the nociceptive fibers, resulting in analgesia.⁹

Full opioid agonists, such as morphine, hydromorphone, and fentanyl exert potent analgesic effects through direct activation of mu receptors. This action demonstrates a dose-dependent relationship between analgesia, euphoria, and respiratory depression. However, individual variability exists based on genetic polymorphism of opioid receptors leading to changes in binding affinities, which clinical manifests in variable sensitivities and responses to opioid therapy.⁹

Specific secondary or associated conditions and complications

Opioids can affect a vast number of organ systems and influence a large number of body functions. Proper patient screening, education, and preemptive treatment of potential side effects aid in maximizing effectiveness while reducing the following side effects and adverse events.

Common side effects of opioids include¹²

• Gastrointestinal (constipation, nausea, emesis, pruritus)
• Bladder dysfunction (post-operative urinary retention)
• Cardiovascular (Increased risk for prolonged QT interval with methadone, hypotension)
• Sleep Dysfunction (Decreased total sleep time, sleep efficiency, delta sleep, and REM sleep)
• Psychological (tolerance, dependence, addiction)
• Central nervous system (impaired cognition, decreased balance, decreased reaction time, hyperalgesia)      
• Endocrine (hypogonadism, androgen deficiency, osteoporosis, amenorrhea)

The most common side effects of opioid use are constipation and nausea (40-95%).¹²

Common side effects of high dosage opioids (>90 mg morphine equivalent daily dose)¹¹

• Higher rates of overdose and death
• Difficulty to control acute pain
• Higher rates of falls and fractures in the elderly
• Opioid-induced hyperalgesia
• Withdrawal hyperalgesia
• Higher rates of endocrinopathy affecting fertility, libido, and drive
• Psychological or pharmacological tolerance

Close management of side effects may include additional medications, such as antiemetics and bowel medications. It is best practice to start a bowel regimen to prevent opioid-induced constipation for someone who is taking opioids.

Sexual dysfunction may be related to the direct effects of opioids or related drug-induced inhibition of the production and release of gonadotropin-releasing hormone and inhibition of testicular testosterone synthesis.

Opioid use in pregnancy can result in stillbirth, poor fetal growth, preterm delivery, or birth defects. For pregnant women already on long-term opioid therapy, abrupt taping can result in the fetus and patient undergoing withdrawal. Pregnant women on opioid treatment should arrange for delivery at a facility capable of treating neonatal withdrawal syndrome.

Special considerations of specific opioids

Codeine

• Avoid in patients with renal disease
• Avoid while pregnant due to crossing of the placenta

Morphine

• Hypotension
• History of obstructive airway diseases due to higher rates of respiratory depression
• History of gastroparesis

Methadone

• QT interval prolongation
• Chronic hypokalemia
• Individuals with liver impairment

Fentanyl

• Individuals with liver impairment
• History of obstructive airway diseases
• Used with concomitant medications that are CYP3A4 inhibitors (macrolides and protease inhibitors)

Tramadol

• Elevated risk for serotonin syndrome
• Higher risk for seizures

Essentials of Assessment

Functional assessment

Pain assessment for opioid prescription: The “Four A’s” of pain assessment are:

• Analgesia – Intensity level using the appropriate pain assessment tool (e.g., numeric rating scale) that is dependent on the patient’s cognition, communication, and or sedation levels; assess at rest versus with activity; acute versus chronic; aggravating and relieving factors; evaluate pertinent medical history; physical exam^{13,14, 15}
• Activities of daily living – assess function by evaluating patient’s ability to ambulate, perform ADLs and self-hygiene; assess restrictions related to the pain;
• Adverse effects – including the presence of sedation, respiratory depression, constipation, and neurotoxicity;
• Aberrant drug taking, characterized¹⁴
  • euphoria
  • taking more medication than prescribed
  • running out of scheduled prescriptions early
  • reporting the ongoing need for greater doses
  • selling or diverting their medications

Risk stratification for potential aberrant behaviors should be based on exploring risk factors for opioid misuse. It is suggested that the risk of prescription drug abuse is most significant when risk factors in 3 categories (i.e., psychosocial factors, drug-related factors, and genetic factors) occur in the same individual¹⁴ The following screening tools can be used to assess such risk factors¹⁴

• Screener and Opioid Assessment for Patients with Pain Revised (SOAPP-R)  
• Opioid Risk Tool    
• Brief Pain Interview
• Diagnosis, Intractability, Risk, and Efficacy (DIRE) score
• Opioid Risk Tool for Opioid Use Disorder (ORT-OUD) 
• CAGE for Alcohol Abuse

Assess controlled substance prescription history utilizing the state prescription drug monitoring program (PDMP) before opioid initiation and regularly during treatment.

• Assess for multiple prescribers of controlled substances
• Assess for early refill requests
• Determine whether opioid dosages are appropriate or if there are dangerous combinations
• Random urine drug tests during office visits

Psychosocial Issues

• Evaluate overall patient distress, underlying psychiatric history, family support
• Understand the patient’s knowledge of pain and its management
• Prior history of treatment of pain and patient’s response to other opioid/non-opioid medications
• Concerns about addiction to pain medications with or without regard to prior history of drug abuse

Goals/Expectations

• Set expectations and determine with the patient the desired levels of pain that will allow the individual to improve function and quality of life while minimizing pain-related restrictions

Laboratory studies

• Compliance testing and monitoring for abuse and diversion are essential. Standard testing includes both a urine screen (immunoassay) and subsequent confirmatory testing (gas chromatography/mass spectrometry) that can confirm the precise type of opiate.
• Urine drug testing should be performed before initiating therapy and at least annually. Clinicians should make the final decision on the frequency of testing based on factors such as behavioral changes and the classification of high-risk patients. Creating an exact schedule for testing may present an obvious timetable that can be manipulated by patients prone to non-compliant behavior^. 
• Urine screens monitor for other agents (cannabinoids, benzodiazepines, amphetamine, cocaine). Clinicians need to understand how to interpret the results of the drug panel tested, such as positive results for medication metabolites.   
• The role of serum testing in opioid monitoring remains controversial.
• Newer strategies, including testing hair, saliva, and other tissue samples, are an evolving area. Biological matrices such as hair may provide a longer detection window than blood or urine and be less invasive; commercially available testing is presently not widely available.
• There is controversial genetic screening for medication metabolism.

Professional issues

An important balance between patient access and reasonable clinical practice is necessary. Patients need access to quality pain management, including the use of controlled substances. However, the clinician should be trained in the indications, contraindications, and management of opioids while also taking the necessary steps to prevent and/or monitor for abuse and diversion. Opioid agreements and open, honest communication can help the patient-provider relationship.¹⁵

Rehabilitation Management and Treatments

Available or current treatment guidelines

The 2022 Center for Disease Control (CDC) clinical practice guidelines have replaced the 2016 CDC guidelines for prescribing opioids in outpatient settings for patients 18 years or older. The guidelines provide guidance for initiating opioid therapy, opioid tapering strategies, consideration for opioid dosages, and nonopioid pharmacologic therapies.

The recommendations do not apply to pain management related to sickle cell disease, cancer-related treatment, palliative care, or end-of-life care. The 2022 guideline aims to promote equitable access to effective, informed, individualized, and safe pain management that improves patients’ function and quality of life while clarifying and reducing the risks associated with opioid use.¹⁷  

Their 12 Recommendations Include

1. Non-opioid therapies are at least as effective as opioids for many common types of acute pain. Clinicians should maximize the use of nonpharmacologic and nonopioid pharmacologic therapies as appropriate for the specific condition and patient and only consider opioid therapy for acute pain if the benefits are anticipated to outweigh the risks to the patient. Before prescribing opioid therapy for acute pain, clinicians should discuss with patients the realistic benefits and known risks of opioid therapy.
2. Non-opioid therapies are preferred for subacute and chronic pain. Clinicians should maximize the use of nonpharmacologic and nonopioid pharmacologic therapies as appropriate for the specific condition and patient and only consider initiating opioid therapy if the expected benefits for pain and function are anticipated to outweigh risks to the patient. Before starting opioid therapy for subacute or chronic pain, clinicians should discuss with patients the realistic benefits and known risks of opioid therapy, should work with patients to establish treatment goals for pain and function, and should consider how opioid therapy will be discontinued if benefits do not outweigh risks.
3. When starting opioid therapy for acute, subacute, or chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release and long-acting (ER/LA) opioids.
4. When opioids are initiated for opioid-naïve patients with acute, subacute, or chronic pain, clinicians should prescribe the lowest effective dosage. If opioids are continued for subacute or chronic pain, clinicians should use caution when prescribing opioids at any dosage, should carefully evaluate individual benefits and risks when considering increasing dosage, and should avoid increasing dosage above levels likely to yield diminishing returns in benefits relative to risks to patients.
5. For patients already receiving opioid therapy, clinicians should carefully weigh the benefits and risks and exercise care when changing the opioid dosage. If the benefits outweigh the risks of continued opioid therapy, clinicians should work closely with patients to optimize nonopioid therapies while continuing opioid therapy. If the benefits do not outweigh the risks of continued opioid therapy, clinicians should optimize other therapies and work closely with patients to gradually taper to lower dosages or, if warranted, based on the individual circumstances of the patient, appropriately taper and discontinue opioids. Unless there are indications of a life-threatening issue, such as warning signs of impending overdose (e.g., confusion, sedation, or slurred speech), opioid therapy should not be discontinued abruptly, and clinicians should not rapidly reduce opioid dosages from higher dosages.
6. When opioids are needed for acute pain, clinicians should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids.
7. Clinicians should evaluate benefits and risks with patients within 1–4 weeks of starting opioid therapy or escalating opioid dosage for subacute or chronic pain. Clinicians should regularly reevaluate the benefits and risks of continued opioid therapy with patients.
8. Before starting and periodically during the continuation of opioid therapy, clinicians should evaluate the risk for opioid-related harms and discuss the risk with patients. Clinicians should work with patients to incorporate into the management plan strategies to mitigate risk, including offering naloxone.
9. When prescribing initial opioid therapy for acute, subacute, or chronic pain, and periodically during opioid therapy for chronic pain, clinicians should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or combinations that put the patient at high risk for overdose.
10. When prescribing opioids for subacute or chronic pain, clinicians should consider the benefits and risks of toxicology testing to assess for prescribed medications as well as other prescribed and nonprescribed controlled substances.
11. Clinicians should use particular caution when prescribing opioid pain medication and benzodiazepines concurrently and consider whether the benefits outweigh the risks of concurrent prescribing of opioids and other central nervous system depressants.
12. Clinicians should offer or arrange treatment with evidence-based medications to treat patients with opioid use disorder. Detoxification on its own, without medications for opioid use disorder, is not recommended for opioid use disorder because of increased risks of resuming drug use, overdose, and overdose death.

Coordination of care

Chronic pain management is best done with a multidisciplinary approach. Opioid use for chronic pain treatment is only one modality for treatment. Coordination of care with physical and occupational therapists can improve function and quality of life. Psychosocial factors can be addressed by psychologists, psychiatrists, social workers, and therapists. Safe opioid prescribing can be supported by referencing state prescription monitoring programs to identify aberrant behaviors or unsafe medication combinations. Using a multidisciplinary approach to chronic pain care can also assist in reducing opioid use.

Patient & family education

Patient and family education may improve outcomes pertinent to achieving short- and long-term goals and may reinforce recognition of behavioral changes, adverse effects, and initiatives essential to developing a genuinely comprehensive pain management program. ASIPP 2017 opioid guidelines state chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function in low doses with appropriate monitoring and understanding of adverse effects.⁸ This message is essential for patient and family education on opioid management for chronic pain conditions to develop expectations and goals.

Cutting Edge/Emerging and Unique Concepts and Practice

Cutting edge concepts and practice

These include:

Drug formulations are designed to deter or resist abusive behaviors.

Risk Evaluation and Mitigation Strategy (REMS) proposals from the DEA/FDA.

The Opioid Analgesic Risk Evaluation and Mitigation Strategy (OA REMS) remains crucial in mitigating risks associated with prescription opioid analgesics. It prioritizes maintaining benefits over risks through education for healthcare providers (HCPs) involved in pain management. Recent developments include initiatives to enhance safety measures and prevent misuse and overdose:

• The FDA initiated open comments under the Support Act on April 21, 2022, empowering the FDA to mandate safe disposal packaging or systems for certain patients receiving opioids or other drugs with a severe risk of abuse or overdose.
• The Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (SUPPORT Act) amended the FDA’s authorizing statute to permit requiring safe disposal measures through a REMS for certain patients.

Regarding the FDA’s proposed expansion of the Risk Map system for controlled substances:

• The FDA aims to expand the existing Risk Map system to develop a comprehensive plan for controlled substances, including premarketing studies, robust post-marketing labeling, and ongoing monitoring of misuse.

Federal and state-controlled substance laws and resources are also important considerations. The Pain and Policy Studies Group websiteoffers information on various United States and international resources. Additionally, Achieving Balance in State Pain Policy: A Progress Report Card, now in its fourth edition, is a valuable resource. Specific public law information can be found in the Controlled Substances Act.

Emerging/unique interventions

Formulations designed to deter abuse or manipulation, such as crushing for snorting or dissolving for injecting, are currently available and in the late stages of development. However, only post-market studies will determine if these formulations effectively reduce the risks of abuse, addiction, or diversion. Post-market studies have shown that abuse-deterrent formulations (ADFs), such as ADF OxyContin, have contributed to a significant decline in abuse, especially via non-oral routes. Despite their potential, concerns about cost and the need for further evidence highlight the importance of ongoing research and monitoring to fully understand ADFs’ impact on opioid misuse and public health.¹⁸

Another emerging intervention for pain management is therapeutic targeting of voltage-gated sodium channels. Voltage-gated sodium channels are the critical molecular determinants of action potential generation and propagation in excitable cells. Human genetics studies have identified that Na1.7 and Na1.8 channel subtypes are expressed in peripheral nociceptive neurons and play a role in transmitting nociceptive signals.¹⁹ Thus, a new medication called VX-548 that selectively inhibits Na 1.8 channels has completed phase 2 clinical trials involving participants with acute pain after abdominoplasty or bunionectomy with promising results.²⁰

Gaps in the Evidence-Based Knowledge

There is a growing recognition that opioids for chronic noncancer pain, particularly in the long-term, are not as safe as previously believed. More high-quality research is required to develop effective prescriber strategies for managing chronic noncancer pain, along with guidance on establishing cost-effective, evidence-based multimodal pain management programs. Additionally, there is a need for a deeper understanding of the misuse and abuse of opioid medications prescribed for pain.

References

1. Webster  L. Chronic Pain and the Opioid Conundrum. Anesthesiology Clinics. 2016; 34: 341-355.
2. Savage SR, Joranson DE, Covington EC, et al. Definitions related to the medical use of opioids: evolution towards universal agreement. J Pain Symptom Manage. 2003;26:655-667.
3. Busse J, Wang L, Kamaledin M, et al. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-Analysis. JAMA. 2018; 320: 2448–60.
4. Mattson CL, Tanz LJ, Quinn K, et al. Trends and Geographic Patterns in Drug and Synthetic Opioid Overdose Deaths — United States, 2013–2019. MMWR Morb Mortal Wkly Rep 2021;70:202–207
5. Ciccaron, D. The Triple Wave Epidemic: Supply and Demand Drivers of the US Opioid Overdose Crisis. The International Journal on Drug Policy. 2019; 71: 183–88.
6. Yong J, Mullins P, Bhattacharyya N. Prevalence of Chronic Pain among Adults in the United States. Pain Journal. 2022; 163: 328.
7. Mills S. Nicolson K, Smith B.  Chronic Pain: A Review of Its Epidemiology and Associated Factors in Population-Based Studies.  BJA: British Journal of Anaesthesia. 2019; 123: 273–83.
8. Manchikanti L, Kaye A, Knezevic N, et al.  Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines  Pain Physician. 2017; 20: 3–92.
9. Trescot A, Datta S, Lee M, et al.  Opioid Pharmacology. Pain Physician. 2008;11: 133-153.
10. Friedman A, Lorifel N. Opioids: Pharmacology, Physiology, and Clinical Implications in Pain Medicine. Physical Medicine and Rehabilitation Clinics of North America. 2020; 31:. 289–303.
11. Ballantyne J. Opioids for the Treatment of Chronic Pain: Mistakes Made, Lessons Learned, and Future Directions. Anesthesia & Analgesia. 2017; 125:1769.
12. Benyamin R, Trescot A, Datta S, et al. Opioid Complications and Side Effects. Pain Physician. 2008; 11:105-120.
13. Popat K, Arvide M, Bird J, et al. Peri-Operative Pain Management. MD Anderson Cancer Center. 2021:
14. Kaye A, Jones M, Kay A, et al. Prescription Opioid Abuse in Chronic Pain: An Updated Review of Opioid Abuse Predictors and Strategies to Curb Opioid Abuse: Part 1. Pain Physician. 2017; 20:93-109.
15. Dowell D, Ragan K, Jones C, et al. CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR Recomm Rep. 2022; 71: 1-95.
16. Knezevic N, Khan O, Beiranvand A, et al. Repeated Quantitative Urine Toxicology Analysis May Improve Chronic Pain Patient Compliance with Opioid Therapy. Pain Physician. 2017; 20;135–45.
17. Dowell D, Ragan K, Jones C, et al. Prescribing Opioids for Pain — The New CDC Clinical Practice Guideline. New England Journal of Medicine. 2022; 387: 2011–13.
18. Cicero TJ, Ellis MS. Abuse-Deterrent Formulations and the Prescription Opioid Abuse Epidemic in the United States: Lessons Learned From OxyContin. JAMA Psychiatry. 2015;72(5):424–430.
19. Nguyen P, Vladimir Y. Towards Structure-Guided Development of Pain Therapeutics Targeting Voltage-Gated Sodium Channels. Frontiers in Pharmacology. 2022; 13:20-32.
20. Jones J, Correll D, Lechner S. Selective Inhibition of NaV1.8 with VX-548 for Acute Pain. The New England Journal of Medicine. 2023; 389: 393–405.

Other Online Resources – Supplemental

Office of National Drug Control Policy. Proper disposal of prescription drugs. Available at: http://www.whitehousedrugpolicy.gov/publications/pdf/prescrip_disposal.pdf. Accessed May 1, 2011.

US Drug Enforcement Administration. Drug scheduling. Available at: http://www.usdoj.gov/dea/pubs/scheduling.html. Accessed May 1, 2011.

Department of Justice Drug Enforcement Administration Office of Diversion Control. DEA pharmacist manual. Available at: http://www.deadiversion.usdoj.gov/pubs/manuals/pharm2/pharm_manual.pdf. Accessed May 1, 2011.

Department of Justice Drug Enforcement Administration Office of Diversion Control. Cases against doctors. Available at: http://www.deadiversion.usdoj.gov/crim_admin_actions/index.html. Accessed May 1, 2011.

Rannazzisi JT, Caverly MW. Department of Justice Drug Enforcement Administration Office of Diversion Control Web site. Practitioner’s manual. Available at: http://www.deadiversion.usdoj.gov/pubs/manuals/pract/index.html. Accessed May 1, 2011.

Federation of State Medical Boards of the US. Model policy for the use of controlled substances for the treatment of pain.Available at: http://www.fsmb.org/pdf/2004_grpol_Controlled_Substances.pdf. Accessed May 1, 2011.

Alliance of State with Prescription Monitoring Programs and National Association of State Controlled Substances Authorities.Prescription monitoring program model act. October 2002. Available at: http://www.nascsa.org/PDF/PMPmodelact02.pdf. Accessed May 1, 2011.

Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines. Febuary 2017. Available at https://pubmed.ncbi.nlm.nih.gov/28226332/. Accessed April 8, 2024.

CDC Clinical Practice Guideline for Prescribing Opioids for Pain. 2022. Available at https://www.cdc.gov/opioids/patients/guideline.html. Accessed April 8, 2024.

Original Version of the Topic

William Anderson, MD. Opioid Management for Chronic Pain. 11/11/2011.

Previous Revision(s) of the Topic

Monika Patel, MD. Opioid Management for Chronic Pain. 9/16/2016.

Arpit Arora, MD. Opioid Management for Chronic Pain. June 29, 2021

Author Disclosure

Thomas Chai, MD
Nothing to Disclose

Royce Copeland, DO
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Angela Nwankwo, MD
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Ashlyn Brown, MD
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Jason Parmar, DO
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Larry C Driver, MD
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