Opioids for Chronic Pain – An Interview with Dr. Webster, Pain Guruby Shaheen E Lakhan, MD, PhD, MEd, MS, FAAN | January 30, 2015
With chronic pain has come a debate on how to treat it, and some controversy on whether opioid use is effective or not. Lynn R. Webster, M.D., is one the nation’s leading researchers and experts in the field of chronic pain management.
Dr. Webster is the Vice President of Scientific Affairs of PRA Health Sciences and immediate past president of the American Academy of Pain Medicine. Practicing medicine for over three decades, Dr. Webster has authored Avoiding Opioid Abuse While Managing Pain: A Guide for Practitioners. As developer of the Opioid Risk Tool (ORT), he is considered a world authority on how to assess patients for abuse risk with opioid medications, and in trying to help physicians safely treat pain patients while actively working within the industry to develop safer and more effective therapies for chronic pain and addiction. Here, I interview Dr. Webster on prescription opioids for pain.
Lakhan: What are the indications for long-term opioid prescriptions?
Webster: Chronic opioid therapy should be reserved for patients who have pain severe enough to warrant a strong analgesic and no other options to effectively relieve the pain. The precise number of people in this category is unclear and is often determined by what a payer is willing to cover, because most alternative treatments are unaffordable to most patients. Chronic opioid therapy can produce side effects, including sexual dysfunction, constipation, hyperalgesia and sleep apnea. Of course exposure to an opioid may also lead to abuse or addiction in a subset of the population with genetic and environmental vulnerabilities.
Lakhan: Are there certain individuals who should NOT be prescribed opioids?
Webster: As with all medications, a risk-benefit analysis is necessary to determine the potential benefit versus harm. People at high risk of harm would be people with an active opioid addiction, significant genetic risks for opioid addiction, abuse of or addiction to other psychoactive drugs, morbid obesity, serious mental health disorders and individuals who are unreliable or who have a history of poor adherence to medical direction. Opioids may be necessary for these people during an acute injury or surgery with appropriate monitoring, but chronic opioid use should be avoided in these populations.
Lakhan: What are the dangers on long-term opioid use?
Webster: “Dangers” implies serious adverse outcomes like addiction or overdose death rather than a common side effect like constipation or sexual dysfunction. The most serious outcome is respiratory depression leading to death. This risk is heightened when combining an opioid with a benzodiazepine or other central nervous system depressant. Respiratory depression can occur if more opioid is circulating when a concomitant medication is added that slows the metabolism of the opioid. Respiratory infections can reduce the pulmonary reserve, increasing the risk of hypoxia and respiratory failure leading to death. That said, even the more common side effects like constipation or sexual dysfunction can cause serious difficulty if not managed.
Conflicting reports have assessed the risk of long-term opioid use in the development of addiction. In general, long-term use of opioids has not been associated with an increased risk of addiction per se. That is because the dose of an opioid and duration of exposure are not necessarily risk factors for opioid addiction. People can be harmed at a low dose or a high dose and with short-term exposure as well as long-term exposure to opioids.
Lakhan: How do patients become addicted to opioids?
Webster: Addiction is a brain disease. Opioid addiction, in contrast to some other types of addiction, has approximately two equal contributions to its expression: 50% genetic and 50% environmental. This means that most people who develop an addiction to an opioid have some genetic vulnerability and an environment that allows or induces the vulnerability to be expressed. There are many single nucleotide polymorphisms (SNPs) that appear to contribute to the genetic vulnerability.
Most people have some of the SNPs, but even those who have a strong genetic vulnerability could be spared an opioid addiction if they live in a protective environment. The environmental factors that contribute to the expression of an addiction are multiple, but stress appears to be one of the more significant contributing factors. Unfortunately, severe pain is one of the most stressful conditions that exists and can trigger the expression of addiction in a genetically vulnerable person. A quick survey of a person’s family can provide some insight into the possible genetic risks to an opioid addiction.
The number of people who are prescribed an opioid and develop addiction is hotly debated. Studies suggest anywhere from 3% to 40% of people prescribed opioids develop an abuse or addiction problem. The reason for such a large range is that the definitions used to define abuse and addiction vary tremendously depending upon who is speaking. There are many biases and prejudices toward people who use opioids for pain. Often, any deviation in expected behavior with using opioids is documented on the spectrum of behaviors associated with addiction.
Lakhan: Where are people sourcing opoids from?
People with opioid addictions can get their supply from a number of different sources. Most opioids obtained for non-medical use are obtained from family or friends who have been prescribed opioids for a legitimate medical purpose. These drugs are either stolen by, sold to, or given to the abuser. Only about 10-15% of opioids used for non-medical purposes are prescribed directly to the abuser.
Lakhan: What measures can be taken to prevent opioid abuse and addiction?
Webster: I think the first step is to understand that as long as any rewarding substance is prescribed, a subset of the population will abuse or become addicted to that substance. This is part of our biology and applies to opioids and many other rewarding drugs used in medicine. However, there are many things we can do to mitigate the harm and reduce the risk of opioid-related aberrant behaviors. In general, prescribers and patients need to understand the risk and be cognizant of the signs of addiction. This requires rudimentary education.
To develop an addiction, a person must be exposed to the drug. Avoiding the use of opioids whenever possible decreases exposure. Decreasing exposure reduces the chance for the disease of addiction to be expressed. Since we cannot know for sure a prioi who is genetically vulnerable, we should only use opioids long term when other alternatives are ineffective or unavailable.
If an opioid is to be prescribed, an assessment for risk factors should be performed followed by close monitoring for aberrant behavior. Addiction can be triggered with the first dose or develop after prolonged exposure. People with a “loaded” genome may express an addiction earlier than those who are spared many of the genetic risks. People who develop an addiction later may have less of a genetic vulnerability, but the stress associated with chronic pain can tip toward destructive use behaviors. Using urine drug testing and prescription drug monitoring is essential to detecting non-adherence, which could be a sign of addiction.
For more on how to prevent opioid addiction see my book, Avoiding Opioid Abuse While Managing Pain
Lakhan: What are the “eight principles” for safer opioid prescribing?
Webster: The most serious adverse outcome from prescribing an opioid is an unintended death from overdose. The eight principles are an evidence-based guide on how to reduce the risk of unintended overdoses if an opioid is prescribed. There are many causes for overdoses, but the eight principles identify the factors that appear to contribute often. If all prescribers understood the eight principles, the number of opioid-related deaths should be reduced.
Lakhan: How do opioid abusers circumvent the deterrent properties of the abuse-deterrent opioid formulations? What is promising in this arena?
Webster: Abuse-deterrent formulations are meant to prevent a manipulation of the formulation that would increase the speed of delivery or amount of the drug to an individual for use in an unintended way. The intention is to decrease the user’s ability to crush and thereby extract the opioid molecule from the formulation, making it more difficult to snort or inject. In an extended-release formulation, the abuse-deterrent properties prevent the conversion to an immediate-release formulation. In other words, they prevent a dose dumping or a bolus of drug to be delivered.
There is debate about whether all extended-release formulations should have abuse-deterrent properties. I personally believe that the FDA should set a deadline for when all ER formulations must meet a minimum standard of abuse-deterrent properties to remain on the market. If this were to occur, the cost of ER formulations would likely increase, but this may be a reasonable trade-off for potentially safer products. Of course, this move will not eliminate all dangers; people can still overdose if they take multiple pills of an abuse-deterrent formulation.
Promising research indicates that some new formulations could be inert if injected, snorted or crushed, meaning the opioid would only be active when taken as directed. If someone takes a higher dose than prescribed, the technology is designed to deactivate the molecule, thereby preventing an overdose. There is even more promising research in development investigating an opioid without rewarding properties or respiratory-depressant effects within the therapeutic range. This would be a major advance in analgesic drug development.
Lakhan: Should prescription drug monitoring, which is currently done on a state level, be nationalized?
Webster: All states but Missouri have prescription drug monitoring programs or plans to develop one. The programs are operated differently from state to state, so criteria for using them will vary. Access to timely information is variable as well. It is important that prescribers have access to interstate data sharing because patients can easily move from one area to another if they intend to deceive the prescriber. In some cases, physicians can access data from prescription monitoring programs in surrounding states by contacting those states, but this takes more time and work than is desirable.
For years there has been a push for a nationally centralized database of prescriptions. However, funding has been lacking to make that happen. States have seen the value in sharing their information with physicians in surrounding areas, so some “exchanges” for states to share their databases have been set up. Ultimately, utilization of the databases is what is important. In most states less than a third of physicians use the databases when prescribing an opioid. This needs to change if we are going to identify most of the “doctor shoppers” and curb the epidemic of drug abuse.
Lakhan: What is the future of opioid research?
Webster: The future of opioid research is exciting. In the not-too-distant future we should be able to replace the current mu agonists with opioids that are not nearly as addictive or associated with the same magnitude of adverse effects. This is a field that is only beginning to produce candidates for further development, but there is real optimism and hope that we will one day have a class of opioid drugs that is closer to the Holy Grail of powerful analgesics without addictive properties than anyone could have dreamed possible.
Lakhan: Any final remarks for our readers?
Webster: The reason we have a problem with opioids is because of the prevalence of severe pain and lack of alternative therapies. Nearly one-third of all Americans have chronic pain. Chronic pain is the most prevalent medical problem today, but we spend less than 1% of the National Institutes of Health research budget on finding safer, more effective therapies. To ultimately solve the opioid problem we will need to find better ways to treat pain. This will require an unprecedented commitment of resources.
We need something like a Manhattan Project. We cannot ignore the millions of Americans whose lives are torn apart by pain or accept the large number of people who are harmed from opioids. After all, each reader of this article is likely to experience chronic pain or be close to someone who does. As of now, chronic pain has the power to alter lives forever. We need a societal commitment to find safer and more effective therapies for mankind’s primal enemy – pain.
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