In 76 trials comparing opioids vs. placebo with follow- up ranging from 1 to 6 months, the reduction in pain scores with opioids (on a 10-point scale) was only 0.69 points, which is below the generally-accepted 2-point minimum clinically important difference for pain. Physical function scores (on a 100-point scale) improved with opioids by 2.04 points, which, again, may not be clinically important. The risk of vomiting with opioids, however, was more than 4 times higher than with placebo. 12 The same meta-analysis compared opioids to non-opioid analgesics including NSAIDs, TCAs, anticonvulsants, and synthetic cannabinoids. No significant differences were found in physical functioning scores for any of the comparisons, and no significant differences were found in pain scores for comparisons with NSAIDs, TCAs, or cannabinoids. 12 Exceptions: chronic opioid use in limited patient subsets Sickle cell disease as an example for which chronic opioid therapy may be appropriate in some patients. The risk for opioid death in patients with sickle cell disease comprises a small fraction of the total number of opioid-related deaths. Opioids were involved in 80,411 overdose deaths in 2021 (75.4% of all drug overdose deaths) 1 . The pain experienced by patients includes both acute and chronic aspects through multiple mechansims that are not completely understood. The American Society of Hematology
2020 guidelines endorses the use of chronic opioid therapy for patients with sickle cell disease with pain that is refractory to multiple other treatments using the lowest effective dose and with regular monitoring. 75,76 Opioid formulations Prescription opioids are available in immediate- release and extended-release/long-acting (ER/ LA) formulations. Immediate-release agents are recommended in opioid-naïve patients and for all acute pain conditions, with ER/LA agents reserved for patients or conditions in which the longer duration of action and smoother pharmacodynamics are preferred. 31 A trial comparing immediate release to an ER/LA opioid did not find evidence that the continuous, time-scheduled use of ER/LA opioids was more effective or safer than intermittent use of the immediate-release opioid. 71 According to the FDA, ER/LA opioids should only be used for patients who tolerate 60 morphine milligram equivalents per day (MMED) for at least one week. 78 Efforts to create formulations with lower risks of abuse have met with limited success. For example, ER Oxymorphone was removed from the market after reports of intravenous abuse of the oral formulation. 79 Abuse-deterrent or tamper-resistant formulations do not prevent patients from developing opioid dependence, opioid use disorder, or simply taking too much of an opioid by mouth. 80,81
Case study 2 Wayne is an 86-year-old who lives at home with his wife. He was diagnosed with ALS 6 months ago, with deterioration occurring first in his diaphragm. He has been experiencing increasing muscle weakness in his legs and uses a walker or a wheelchair to get around in his home. He uses a bilevel positive airway pressure device except when eating or bathing and finds it helpful. He takes the following medications: fish oil, a statin, a thiazide diuretic, and a non-benzodiazepine sedative to help him sleep. Lately he has been complaining of pain and stiffness in both of his knees and hips, which interferes with his sleep. He is physically deconditioned due to a lack of exercise, and has become increasingly withdrawn socially, which worries his wife and family members. He asks if you can prescribe something to ease his pain. Questions: 1. Is Wayne a good candidate for an ER/LA opioid? Why, or why not? _______________________________________________________________________________________________ 2. Is he a better candidate for an immediate-release opioid? Why or why not? _______________________________________________________________________________________________ 3. Would Wayne’s current medication need to be adjusted if he were to be prescribed an ER/LA opioid? _______________________________________________________________________________________________ 4. What kinds of non-opioid treatments might be tried to help Wayne with his pain? _______________________________________________________________________________________________ Atypical opioids: tramadol and tapentadol
As noted above, tramadol is classified as Schedule IV, which has led some to view it as less potent or safer than other opioids. The 2022 National Survey on Drug Use and Health shows that of the 14.6 million people aged 12 and older who used tramadol products (e.g., Ultram, Ultram ER, Ultracet) in the past year, 9.4% of these individuals misused the drug. In addition, a 2019 cohort study of 88,902 patients with osteoarthritis showed increased risks of death at one year compared to NSAIDs naproxen, diclofenac, and celecoxib. 84
Tramadol and tapentadol are mu receptor agonists and norepinephrine reuptake inhibitors. Their mechanisms of action are unknown, but their analgesic effects are similar to morphine. Patients taking tramadol should be monitored for nausea, vomiting, constipation, and drowsiness, all of which are similar to side effects with opioids. 82 There is potential risk of serotonin syndrome when tramadol is combined with SSRIs, SNRIs, or tricyclic antidepressants. 83
Book Code: MDAZ1124
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