II. Contraindications: Relative
- Substance Abuse (especially Narcotic Abuse)
 - Severe character pathology or Personality Disorder
 - Chaotic social environment
 
III. Adverse Effects: Opioids
- Cardiovascular events (including sudden death)
- QT Prolongation occurs most commonly with Methadone, Buprenorphine, Oxycodone
 - Avoid combining with other agents that potentiate Arrhythmia risk (e.g. Methadone and Diazepam)
 
 - Constipation and Abdominal Pain
 - 
                          Major Depression and Suicidality Risk
- Major Depression risk increases 25% with use >90 days and 50% with use >180 days
 - Avoid combining Opioids with other CNS Depressants
 - Limit Opioid dosing and quantity with appropriate follow-up
 - Monitor for aggression and impulsivity (Suicidality risks)
 - Encourage mental health referral (also beneficial in Chronic Pain Management)
 - Use Antidepressants as appropriate, but avoid agents with risk in Overdose (e.g. Tricyclic Antidepressants)
 
 - Hypothalamic-Pituitary hypofunction
- Decreases gonadal Hormones including Testosterone
 - Consider obtaining Hormone levels prior to initiating Chronic Opioids
 - Buprenorphine has less Hormone suppression than Methadone
 - Hormonal levels improve on tapering Opioid dose
 - Rhodin (2010) Clin J Pain 26(5):374-80 +PMID:20473043 [PubMed]
 
 - 
                          Opioid-Induced Hyperalgesia
                          
- Opioids may paradoxically worsen pain, and increase pain sensitivity with chronic use
 - Taper dose and re-evaluate after Opioid Withdrawal completed at 2-4 weeks
 
 - 
                          Opioid Misuse and abuse
- See Complications below
 - Refer to pain management
 - Refer to Chemical Dependency
 - Naloxone prescription for home (for emergency prn use)
 - Suboxone is less likely to be misused or abused (but can still be abused via snorting or IV)
 
 - 
                          Opioid Dependence and tolerance
- See Opioid Withdrawal
 - See Opioid Dependence
 - Do not exceed >120 mg/day of total Morphine Equivalents
- CDC recommends limiting Opioids to 90 mg/day of total Morphine Equivalents in non-Cancer Pain
 
 - Taper Opioids
- Involve pain management to consider transition to other agents or tapering medication
 - Treat Opioid Withdrawal with non-controlled substances (e.g. Antiemetics, Muscle relaxants, Clonidine)
 
 
 - 
                          Opioid Overdose and apnea risk
- Limit or taper Opioids if comorbid apnea risk (Sleep Apnea, binge drinking or excessive Alcohol use)
 - Avoid combining CNS Depressants (e.g. Benzodiazepines)
 - Caution patients not to cut patches, crush or chew long-acting Opioids (and other misuse)
 - Naloxone prescription for home (for emergency prn use)
 
 
IV. Complications
- 
                          Overdose Risk Factors
- Sleep Apnea
 - Congestive Heart Failure
 - Lung disease
 - Sedative-Hypnotics (e.g. Benzodiazepines)
 - Problem Alcohol use
 - Comorbid psychiatric illness (e.g. Major Depression)
 
 - 
                          Opioid Misuse or Opioid Use Disorder Risk Factors
- See Opioid Risk Tool
 - Narcotic Seeking Behavior
 - Personal or Family History of Substance Abuse
 - Psychiatric comorbidity
 - Preadolescent history of sexual abuse
 
 
V. Guidelines: Chronic Opioid Use Guidelines in Non-Cancer Chronic Pain
- Observe for Narcotic Seeking Behavior
- See Prescription Drug Monitoring Programs link below
 
 - Avoid confusing Pseudo-addiction for addiction
- Avoid inadequate treatment of pain
 
 - Single clinician should primarily manage patient
 - Incorporate Controlled Substance Agreement consistently (renew annually)
 - Maintain Opioid use flow sheet
 - Titrate to pain relief and adverse effects
- Reevaluate on a 1-4 week basis
 - Avoid total daily Opioid dose >120 MME
 
 - Documentation is key (see follow-up below)
 - Convert short-acting Opioids to long-acting Opioids
 - Use in combination with other therapy
- See Chronic Pain Management
 - Non-Opioid Analgesics
 - Make use of non-pharmacologic modalities
 
 - Treat Opioid Adverse Effects prophylactically
 - Be aware of pseudotolerance
- Opioid appears to fail to control pain
 - Pain flares are countered with escalated dosing and not returning to prior baseline
 - Set expectations with patient
- Medication returns to prior baseline after brief flare
 - Unauthorized dosage increases are not allowed
 
 
 - Be aware of biases related to cohorts more likely to be under-treated for pain
- People of color
 - LGBTQ
 - Lower socioeconomic status or education level
 - Low income residence
 - Cognitive Impairment
 - Language barriers
 - Underlying mental health disorders
 - Recovered Substance Use Disorder
 - Sickle Cell Anemia
 
 
VI. Protocol: Initial Assessment for non-cancer pain Chronic Opioid therapy
- Select appropriate patients for Chronic Opioids
- Evaluate for multiple sources for controlled substances (PDMP)
 - Screen patients for Opioid Misuse or Opioid Abuse (Opioid Use Disorder)
- See DIRE Score
 - See Opioid Risk Tool
 - Consider Buprenorphine
 
 - Evaluate for risk of respiratory depression associated with other substance use
 
 - Select appropriate conditions for Chronic Opioids
- Opioid responsive conditions (partially)
- Musculoskeletal pain
 - Peripheral Neuropathy
 - Postherpetic Neuralgia
 
 - Opioid poorly responsive conditions (visceral pain, central pain)
 
 - Opioid responsive conditions (partially)
 - Select appropriate agent
- Opioids are adjuncts to primary Non-Opioid Analgesics and non-medication pain management
 - Start with short-acting Opioids
- Morphine 7.5 to 15 mg orally every 4 hours (may titrate up to 30 mg every 4 hours)
- Preferred due to less euphoria than with Oxycodone or Hydrocodone
 
 - Oxycodone 5 to 10 mg orally every 6 hours
- Preferred over combination agents with Acetaminophen (e.g. Percocet, Vicodin)
 - Allows for scheduled dosing of Non-Opioid Analgesics (e.g. Acetaminophen)
 
 
 - Morphine 7.5 to 15 mg orally every 4 hours (may titrate up to 30 mg every 4 hours)
 - May advance to long-acting Opioids
- MS Contin (Morphine long acting)
- Preferred over Oxycontin which is associated with high abuse potential
 - Avoid in Renal Failure
 
 - Oxycontin (Oxycodone long acting)
- High abuse potential
 
 - Transdermal Fentanyl
- Expensive, risk of tolerance, variable absorption
 
 
 - MS Contin (Morphine long acting)
 - Buprenorphine (transdermal or combined with Naloxone in Suboxone SL)
- Effective Analgesic with lower tolerance risk and lower abuse risk
 - Used in both Chronic Pain Management and Opioid Use Disorder
 - Special prescriber training is no longer required
 
 - Methadone
- Very effective, with less tolerance risk and inexpensive
 - Do not prescribe to patients at risk for Overdose (increased risk of death)
 - Requires knowledgable prescriber familiar with agent
 - Risk of QT Prolongation
 
 
 - Complete prerequisites at initial visit
- Controlled Medication Agreement (Narcotic Contract)
 - Urine Drug Screen
 
 - Educate regarding expectations
- Review pain control expectations
- Expect a 20% pain reduction at best
 - See Chronic Pain Management
 
 - Review escalating and tapering the dose
 - Review rules and protocol when non-compliant
 
 - Review pain control expectations
 - Review Chronic Pain Flare Management
- Flares are same pain type and same location with an increase in intensity
 
 
VII. Protocol: Follow-up Visits
- Schedule follow-ups
- Initial: Reevaluate on a 1-4 week basis
 - Later: Reevaluate every 3 months
 
 - Documentation: 4A's
- Analgesia
- Document pain level (scale of 1 to 10)
 
 - Adverse Effects
- Document Opioid side effects (e.g. Constipation, Nausea or Vomiting, sedation)
 
 - Activity Level
 - Adherence
- Annually renew Controlled Medication Agreement (Narcotic Contract)
 - Document compliance with prescribed therapy (see pill counts below)
 - Last physical therapy visit
 - Last mental health provider visit
 
 
 - Analgesia
 - Documentation: Comorbidity
- Reassess DIRE Score
- Evaluate for Opioid Use Disorder potential
 - Consider Opioid discontinuation or transition to Buprenorphine
 
 - Major Depression (consider PHQ-9)
 - Anxiety Disorder (consider GAD-7)
 - Sleep Disorders
 - Pregnancy
 
 - Reassess DIRE Score
 - Monitoring
- Urine Drug Screen
 - Pill Counts
- Patient should bring pill bottles to each visit
 
 
 - Stopping or tapering Opioid therapy
- See indications below
 - For a compliant patient without drug misuse, but without benefit at higher dose Opioid
- Consider supplying patient with short acting agents for breakthrough pain on titration
 - Consider supplying patient with smaller increment doses of total daily dose
- Supply four 15 mg ER in place of each 60 mg ER
 
 
 - For a noncompliant patient (rapid taper)
- Print the following taper (or similar) for the patient to follow
 - First, discontinue the long acting agent immediately (do not refill)
 - Then taper frequency and dose of short-acting agent
- Example for patient on 80 mg of short acting Oxycodone 5mg (taper with #68 tabs)
 - Oxycodone 10 mg every 3 hours for 2 days (#32 of 5 mg tabs)
 - Oxycodone 10 mg every 4 hours for 1 day (#12 of 5 mg tabs)
 - Oxycodone 10 mg every 6 hours for 1 day (#8 of 5 mg tabs)
 - Oxycodone 10 mg every 8 hours for 1 day (#6 of 5 mg tabs)
 - Oxycodone 5 mg every 8 hours for 2 days (#6 of 5 mg tabs)
 - Oxycodone 5 mg every 12 hours for 1 day (#2 of 5 mg tabs)
 - Oxycodone 5 mg daily for 2 days (#2 of 5 mg tabs)
 - Stop medication
 
 - Reference
- Gazelka (2017) How to get your difficult patients off Opioids, Mayo Clinical Reviews, Rochester, MN
 
 
 - For a patient with misuse (addiction, diversion)
- Stop all Opioids immediately and no refills
 - Consider Buprenorphine for Opioid Use Disorder
 
 
 
VIII. Protocol: Stopping or tapering Chronic Opioids
- See Opioid Withdrawal
 - 
                          General indications to stop or taper Opioids
- DIRE Score falls below 14
 - Marginal pain control or decreasing function (or lack of improvement with Opioid)
 - Non-compliance with prescriptions or with self-care
 
 - Tapering Opioids to lower doses may improve quality of life and function
- Pain often does not worsen despite decreasing dose
 
 - Indications to immediately stop Chronic Opioids
- Threatening or aggressive behavior toward clinic staff or provider
 - Confirmed diversion, prescription forgery, or obtaining Opioids from multiple sources
 - Confirmed Illicit Drug use (including Marijuana)
 
 - Indications to rapidly taper Chronic Opioids (10-20% weekly)
- Repeated early refill requests despite adequate titration of long-acting Opioids
 - Intoxication or serious adverse effects (e.g. Altered Level of Consciousness)
 - Opioid-Induced Hyperalgesia
 - Broken Controlled Substance Agreement
 
 - Indications to gradually taper Chronic Opioids (5-10% every 2 to 4 weeks; no more often than every week)
- Morphine Equivalent dose >100 mg/day without clear improvement in pain or function
 - Persistent significant adverse effects despite Opioid rotation
 - Functional goals not met
- Less than 30% improvement in daily activities or pain severity from time of starting Opioids
 - Less than 30% improvement in daily activities or pain severity from time of last increase in dose
 
 
 - Anticipatory Guidance (what to expect with withdrawal)
- See Opioid Withdrawal
 - Opioid Withdrawal is uncomfortable, but not life threatening (unlike Alcohol and Benzodiazepines)
 - However, Opioid Use Disorder (OUD) is life threatening due to high Overdose risk with street Opioids
- See Opioid Withdrawal Management with Buprenorphine
 - OUD risk is higher when discontinuing Opioids if daily use has been >=60 MME
 
 
 
IX. Resources
- Prescription Drug Monitoring Programs (alliance of states sites)
 
X. References
- (2015) Presc Lett 22(12):68
 - (2014) Presc Lett 21(12): 67
 - Sokolove (2001) CMEA Medicine Lecture, San Diego
 - Lembke (2016) Am Fam Physician 93(12): 982-90 [PubMed]
 - Berland (2012) Am Fam Physician 86(3): 252-8 [PubMed]
 - Sonoda (2025) Am Fam Physician 111(6): 508-14 [PubMed]