Reports

VEGF Inhibitor Treatment for Age-related Macular Degeneration
Remission with Complete Mucosal Healing Is the Emerging Treatment Goal for Ulcerative Colitis and Crohn’s Disease

Pain Treatment: Focus on Abuse Potential

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 28th Annual Meeting of the American Academy of Pain Medicine

Palm Springs, California / February 22-26, 2012

Palm Springs - The potential for abuse is one of the most important stumbling blocks for appropriate use of opioids. Even though there is very little risk of dependence when opioids are used in a structured pain management protocol, inadequate pain control can permit chronic pain pathways to form, creating a persistent and sustained desire for pain relief and susceptibility to dependence. One of the causes of inadequate pain control and an ironic source of risk of abuse is this fear of dependence, which is common to physicians and patients. Consequently, patients may take, or physicians may prescribe, low and inadequate opioid doses for pain control, or patients may remain non-compliant or inadequately compliant for pain control during the critical acute period of pain suppression. While newer formulated opioids appear to have less potential for abuse, the first defense is adequate control of acute pain in the context of a rehabilitation strategy.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

Opioid analgesics play a critical role in the management of moderate to severe pain because of their potency. This is important, because the ability to render patients pain-free during the acute recovery period is now recognized as critical to the physiologic and psychological recovery from trauma. It is now believed that reluctance to offer adequate pain relief is a major source of the risk of becoming dependent, essentially promoting the risk that this reluctance is meant to avoid.

“There is evidence that untreated or poorly treated acute pain increases the inflammatory and immunosuppressive responses that can damage the nervous system independent of the trauma that caused the pain initially,” reported Dr. Chester C. Buckenmaier, Walter Reed Army Medical Center, Washington, DC. The answer is not to avoid opioids but to use them judiciously.

Lowering Abuse Potential: RADARS Findings

However, opioids are not interchangeable. For example, oxycodone has been found to be more effective than morphine for visceral pain, while hydrocodone, which is less potent than either, is often used for less severe forms of acute pain. A more recently released opioid, tapentadol, which also modifies pain through inhibition of norepinephrine uptake, was found to be as potent as oxycodone in the phase III trial that led to regulatory approval, but it was better tolerated. New data suggest that tapentadol immediate release (IR) may also have a lower potential for abuse in routine clinical use, perhaps due to its dual mechanisms of action.

“Abuse and diversion rates for tapentadol IR were very low during the first 18 months after its launch and did not change significantly over time, despite increasing availability through legitimate channels,” reported Dr. Richard Dart, Rocky Mountain Poison and Drug Center, University of Colorado School of Medicine, Denver. Presenting data from the Researched Abuse, Diversion and Addiction-Related Surveillance System (RADARS) at the AAPM meeting, Dr. Dart explained that unlike previously available opioids, the abuse and conversion curves have remained flat since this agent was released.

The RADARS program measures rates of abuse and diversion for controlled substances throughout the US by collating data from multiple sources, including a police-based surveillance system, data collected from substance abuse treatment programs and poison registries that collect complaints from patients exposed to controlled substances. While the RADARS program was developed specifically for post-marketing surveillance of prescription drug abuse, tapentadol is the first agent that has been consistently monitored from the time of regulatory approval. While not a controlled comparison of drug abuse among opioids, the RADARS system does allow differences in trends to be observed.

In the data presented at the AAPM, rates of abuse and diversion were evaluated over 18 months from the time tapentadol was released in June 2009. Over that period, prescriptions for tapentadol increased by approximately 70,000 for every 3-month period. Yet the drug diversion rates over time remained flat at approximately 0.1 per 100,000 population. Over the same period, the diversion rates for hydrocodone also remained steady but were about twice as great (0.2 per 100,000) while the diversion rates for oxycodone were approximately 5 times higher (fluctuating between 0.4 and 0.6 per 100,000).

Similar differences were observed between these drugs when monitored for abuse. “Non-medical usage rates for tapentadol IR per 100,000 population were extremely low and did not change significantly over time (P=0.867). The values ranged from 0 to 0.015. For comparison, the range for oxycodone was 0.731 to 1.217, and the range for hydrocodone was 0.759 to 1.262,” Dr. Dart reported. He also noted that the rate of patients entering opioid treatment programs for abuse remained stable and negligible over the period of data collection.

“Data from all of the RADARS surveillance programs using the population denominator indicate that tapentadol IR is creating less public health burden, such as arrests, admissions for public detox programs or calls to poison centres than oxycodone and hydrocodone,” Dr. Dart added.

Findings in College Students

Similar data were produced by a separate RADARS program limited to college students, who have demonstrated relatively high rates of non-medical use of prescription drugs in the past. The pattern in this population was of particular interest because the highest rate of non-medical use was in the initial period after regulatory approval. An initial spike was followed by a highly significant decrease (P<0.001) over the subsequent observation period. Overall, while marijuana was the most commonly used substance in this database, reported by 21.2% of those surveyed, hydrocodone was the most common prescription opioid used for a non-medical purpose (6.0%). Non-medical tapentadol IR use was reported by 0.8%.

“The hypothesis is that the early peak of non-medical tapentadol IR was the result of an initial period of experimentation,” Dr. Dart told delegates. He noted that several factors support this hypothesis, including the fact that the majority of non-medical users also reported non-medical use of other controlled substances.

Pain Control as an Independent
End Point for Improved Outcome

The consequences of abuse and diversion are serious for those at risk of dependency and for society as a whole, but the clinical importance of developing agents with a low risk of abuse may be greater confidence among physicians and patients for their use at therapeutic doses. This is important because the greatest risk for chronic pain leading to analgesic dependence is inadequate acute pain control, according to Dr. Buckenmaier.

Due to the potential for agents with a lower abuse potential to increase the confidence of physicians and patients in their safety, other strategies are being pursued. For example, phase I data were presented on NKTR-181, an opioid receptor agonist designed to slow the rate of uptake in the central nervous system (CNS). The importance of this property is that the abuse properties of opioid analgesics are believed to relate to their rapid entry into the CNS. Presenting some of the new data on this agent, Dr. Kathleen Gogas, clinical researcher, Nektar Therapeutics, San Francisco, California, indicated that the initial clinical data support experimental evidence that this opioid agent preserves analgesia while not only offering a lower risk of abuse but also reducing CNS-related side effects, such as sedation.

In the phase I study, which tested NKTR-181 in 60 healthy volunteers over 8 days, there were favourable pharmacokinetics and a high degree of tolerability even at the highest dose tested. Most importantly, the activity in the CNS, as measured with miosis, was significantly delayed by about 2 hours with the activity in the plasma. These results have already encouraged a full development program. Again, the goal will be to provide the same degree of pain control as oxycodone but with a safety profile that will better reassure patients and physicians.

This is an important step, as confirmed by Dr. Laura Clark, University of Louisville, Kentucky, in a symposium on acute pain management at the AAPM. She stated that physician reluctance to offer effective pain control has been a barrier to optimal outcomes. Although education of physicians is needed, a pain service has been created at her institution to standardize care. She cited published studies suggesting that improved pain control reduces morbidities and the risk of developing a chronic pain syndrome.

“Pain control is therapeutic, it is not just being nice. There needs to be a complete reorientation that recognizes pain control as an independent end point for improved outcome,” Dr. Clark told delegates. At most institutions, pain medicines are typically provided by the treating physician, who often fails to ask for a pain consultation even when patients report persistent discomfort. She suggested the need for a paradigm shift.

“An acute pain service can see these patients without waiting for a physician to ask for help. This can be an important step forward in making sure that pain is being adequately addressed from the beginning,” she emphasized.

Summary

The fear of opioid abuse can, in some circumstances, be a direct or at least an indirect cause of opioid dependence. Patients who do not receive adequate pain control have a much higher risk of developing a chronic pain syndrome. Opioids have a low potential for abuse when used appropriately, and it may be possible to further circumvent this risk with newer agents that are not fully dependent on the opioid mechanism of action. While employing opioids that are less likely to encourage diversional or recreational use is important from the perspective of public safety, progress in understanding the value of adequate pain control may be the best defense against dependence in patients who initiate therapy for pain control. 

 

We Appreciate Your Feedback

Please take 30 seconds to help us better understand your educational needs.