From 1999-2014, more than 165,000 people have died from prescription opioid overdose in the U.S.—outstripping deaths from illicit substance use. This trend mirrors the increased prescribing of opioid medications at high doses over long periods of time to treat chronic, non-cancer pain (CNCP). Contributing factors include concerted efforts to answer concerns about the undertreatment of pain; aggressive marketing by pharmaceutical companies attesting to the safety of prescription opioids for long term use; escalating drug doses to address perceived tolerance to the drugs’ analgesic effect; lack of awareness of effective, non-opioid based pharmacologic treatments (e.g., select anticonvulsants and antidepressants); and lack of access to effective non-pharmacologic treatments (e.g., cognitive-behavioral therapy (CBT)). In March of this year, the Centers for Disease Control (CDC) responded to this crisis with a set of Guidelines for Prescribing Opioids for Chronic Pain. The document assesses the evidence regarding the risks and benefits of using opioids in the treatment of CNCP in the primary care setting (outside of the setting of end of life). The authors acknowledge that there is insufficient evidence in many areas to guide practice, and, where there is evidence, it is often only of fair quality. Yet the sense of urgency to reverse the trend in prescription opioid related deaths, the authors believe, outweighs the desire for higher quality data to guide practice at this time. So what does the CDC conclude from the available science when it comes to the use of opioids in treating CNCP (defined as pain lasting greater than three months or past the time of normal tissue healing)? The document assesses the clinical evidence in five areas: 1. Effectiveness: There is no evidence to support the effectiveness of opioids for long-term therapy (≥ 1 year) of CNCP when it comes to impact on pain level, function or quality of life. 2. Risk: Long-term opioid therapy is associated with a dosedependent risk of abuse and overdose. Overdose risk seems to increase dramatically at doses as low as 50 mg morphine equivalents (MME)/day with a hazard ratio as high as 3.73 in some studies compared to doses less than 20 MME/day. Additionally, there is some evidence pointing to increased risk of cardiovascular events when using opioids. 3. Dosing: There is inconsistent evidence about the risk of using extended release/long acting (ER/LA) formulations compared with immediate release (IR) dosing. When compared to extended release morphine, this uncertainty extends to the use of methadone for CNCP therapy with evidence pointing to increased overdose risk, lower overall risk of mortality and no risk difference.
4. Risk Prediction and Mitigation: Available tools to assess opioid abuse and misuse tools at the initiation of therapy (e.g., Opioid Risk Tool and Screener and Opioid Assessment for Patients with Pain-Revised) have low specificity and sensitivity. No evidence exists to guide the use of Prescription Drug Monitoring Programs (PDMP), opiate management plans, urine drug testing (UDT), pill counts, or abuse-deterrent formulations in mitigating the risk of misuse, abuse, or overdose. 5. Acute Pain: There is evidence to suggest that the use of opioids in treating acute surgical pain or pain related to trauma increases the likelihood of ongoing use at one year.
ULTIMATELY, THE DOCUMENT’S FINAL RECOMMENDATIONS ARE BASED ON “CONTEXTUAL EVIDENCE” IN THE FOLLOWING AREAS: Nonpharmacologic and Nonopioid Pharmacologic Treatments: In studies lasting up to six months, CBT, exercise, and combined movement and behavioral treatments (compared to single modality therapy) reduced pain and improved function. In addition, the document refers to several other guidelines that indicate non-opioid analgesics (acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors); select anticonvulsants (gabapentin and pregabalin); and select antidepressants (tricyclics and serotonin norepinephrine reuptake inhibitors) as first or second line treatments. The potential harm of these medications (specifically, acetaminophen and NSAIDs) is considered to be substantially less than the risk of opioids. Additional Data On Opioid Risk and Risk Mitigation: Based on the review of additional studies not included in the clinical review, the authors take a firmer position on the disproportionate association of methadone in up to one third of opioid related deaths despite representing <2% of opioid prescriptions outside of opioid treatment programs. They also point to time-scheduled as opposed to as needed dosing of opioids leading to higher daily doses over time. Some additional risk factors for harm or overdose highlighted include: co-prescription of benzodiazepines, sleep apnea, renal or hepatic insufficiency, age ≥ 65, depression, and substance abuse/dependence. When it comes to risk stratification, the authors suggest that PDMP and UDT, while not supported by clinical evidence, may help identify situations that are high risk for harm or overdose. They do, however; acknowledge the limitations of these tools including the cumbersome nature of using PDMPs and the potential for misinterpretation of UDT results potentially leading to inappropriate clinical decisions. When it comes to risk mitigation, the authors extrapolate from the successes of naloxone distribution in community-based over-dose prevention programs targeted to substance users in lowering overdose deaths as a potential strategy for decreasing overdose from prescription opioids. Finally, the authors found little to no evidence at this point to subMAY / JUNE 2016 | THE BULLETIN | 19