Table 5: Chronic pain patients vs. patients with an OUD 137
Patient with chronic pain
Patient with an opioid use disorder
Medication use is not out of control Medication use improves quality of life
Medication use is out of control Medication use impairs quality of life
Wants to decrease medication if adverse effects develop
Medication use continues or increases despite adverse effects
Is concerned about the physical problem being treated with the drug
Unaware of or in denial about any problems that develop as a result of drug treatment
Follows the practitioner-patient agreement for use of the opioid
Does not follow opioid agreement
May have left over medication
Does not have leftover medication Loses prescriptions Always has a story about why more drug is needed
Treatment Termination Reasons for discontinuing an opioid analgesic can include the healing of or recovery from an injury, medical procedure, or condition; intolerable side effects; lack of response; or discovery of misuse of medications. Regardless of the reason, termination should be accomplished so as to minimize unpleasant withdrawal symptoms by tapering the opioid medication slowly, by carefully changing to a new formulation, or by effectively treating an opioid use disorder if it has developed. Approaches to weaning range from a slow 10% reduction per week to a more aggressive 25 to 50% reduction every few days. 28 In general, a slower taper will produce fewer unpleasant symptoms of withdrawal; however, this may not be the safe course of action for a patient experiencing side effects or who has OUD. Opioid therapy must be discontinued or re- evaluated whenever the risk of therapy is deemed to outweigh the benefits being provided. A clinician may choose to continue opioid treatment with intensified monitoring, counseling, and careful documentation if it is deemed in the best interest of the patient. This requires, however, careful consideration and a well-documented risk management plan that addresses the greater resources necessary for opioid continuation following evidence of misuse. If termination of the physician/patient relationship is deemed necessary (though it rarely is), clinicians must ensure that the patient is transferred to the care of another physician or provider and ensure that the patient has adequate medications to avoid unnecessary risk, such as from uncontrolled or unpleasant withdrawal. Practitioners can be held accountable for patient abandonment if medical care is discontinued without justification or adequate provision for subsequent care. Caution with dose escalation When escalating opioid doses, be aware of two possible critical daily thresholds—50 and 90 MMED. 34 According to the CDC, doses >50 MMED are associated with more than double the risk of overdose compared to patients on <50 MMED. 31
For patients on >90 MMED, a 9-fold increase in mortality risk was observed compared with the lowest opioid doses. Ninety MMED is considered by several guidelines as a “red flag” dose beyond which careful assessment, more frequent monitoring, and documentation of expected benefits are required (note, however, that this limit doesn’t apply to patients with severe cancer pain or end-of-life pain). The total MMED for all prescribed opioids should be used (MMED is automatically calculated on many state PDMP reports). Physician clinical judgment is also important in determining daily thresholds and the CDC limits can be used as a guide. Role of ER/LA opioids and methadone ER/LA opioids include methadone, transdermal fentanyl, and extended-release versions of opioids such as oxycodone, oxymorphone, hydrocodone, and morphine. A 2015 study found a higher risk for overdose among patients initiating treatment with ER/LA opioids than among those initiating treatment with immediate-release opioids. 124 As noted above, continuous, time-scheduled use of ER/LA opioids is not more effective or safer than intermittent use of immediate-release opioids, and ER/ LA opioids increase risks for opioid misuse or addiction. 31 The 2016 CDC guidelines suggest that ER/LA opioids should be reserved for severe, continuous pain and should be considered only for patients who have received immediate-release opioids daily for at least 1 week. 31 Additional caution is required when prescribing ER/LA opioids in older adults or patients with renal or hepatic dysfunction because decreased clearance of drugs among these patients can lead to accumulation of drugs to toxic levels and persistence in the body for longer durations. When an ER/LA opioid is prescribed in the primary care setting, using an agent with predictable pharmacokinetics and pharmacodynamics is preferred to minimize unintentional overdose risk (i.e., the unusual characteristics of methadone and transdermal fentanyl make safe prescribing of these medications for pain more challenging). 31
The use of methadone for chronic pain in primary care should generally be avoided because of higher methadone-related risks for QTc prolongation and fatal arrhythmias. 31 Equianalgesic dose ratios are highly variable with methadone, making conversion from other opioids difficult, with attendant increased risk of overdose. While methadone-related death rates decreased 9% from 2014 to 2015 overall, the rate increased in people ≥65 years of age. 139 If methadone or transdermal fentanyl is considered, refer patients to pain management specialists with expertise in using this medication. BEFORE MOVING ONTO THE NEXT SECTION, PLEASE COMPLETE CASE STUDY 5 ON THE NEXT PAGE. Protecting against opioid-induced adverse events Prophylaxis for constipation—the most common opioid-induced adverse event—has been facilitated by the approval of methylnaltrexone subcutaneous administration and naloxegol oral administration for patients with chronic non-cancer pain. Other, less expensive medications like senna and docusate, are also effective to guard against constipation. Both male and female patients on long-term opioid therapy are at risk for hypogonadism, thus current guidelines suggest that the endocrine function of all patients should be assessed at the start of long-term opioid therapy and at least annually thereafter. Naloxone for opioid overdose Naloxone (e.g., Narcan) is an opioid antagonist that quickly reverses the effects of opioid overdose. Naloxone is increasingly available to first responders, patients, and friends and family members of those prescribed opioids, and a generic formulation of nasal-spray naloxone was approved by the FDA in April, 2019. 141
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