REMS is an acronym for Risk Evaluation and Mitigation Strategy. It is an FDA initiative to deal with the risks associated with certain medications. I first encountered this new concept because one of my lectures is on the current opioid epidemic and looking at the potential risks of opioids. The FDA has an REMS section on their web site including a list of all currently approved REMS. For the purpose of this post I am going to focus on the REMS for Extended Release and Long Acting Opioids. The actual document is 42 pages long. I read it twice and really cannot see anything in the document that would detect the major problems with opioids or potentially prevent those problems. It suggests a thorough evaluation of the type than many primary care physicians no longer have the time to do. The basic elements of a complete history and physical exam, pain diagnosis and examination for addiction and psychiatric comorbidity needs to be taken in the context that substantial numbers of patients with psychiatric diagnoses are now diagnosed by a symptom checklist that is checked off in about 2 minutes. If there is any take home message from this REMs it should be that chronic pain requiring opioid therapy should be referred to a specialty center where they have the time and staff to do the required assessment.
The biggest misconception here seems to be that patients are accurate reporters and they have no unconscious agenda. It leads me to question whether the FDA employs any psychiatrists. It also highlights a naive approach to medicine that suggests physicians and patients are automatons who are basically reading and completing checklists. The complete checklist suggests the diagnosis. On what planet does this happen? With regard to the population of patients with an addiction seeking treatment of chronic pain with opioids, the following graphic may apply.
National Survey on Drug Use and Health. The sample size is 70,000 persons, but the conclusions in the diagram are all drawn from the survey and have the usual limitations. What the diagram shows is that most people who believe they need treatment for an addiction do not make an effort to get it. The NSDUH looks at detailed information across a number of treatment settings and reasons for not accessing treatment.
I use the above diagram when I am taking with primary care physicians or residents about the situation where they are trying to determine whether or not it is safe to prescribed opioids for chronic pain. I point out that the people they are seeing in their office probably resemble the sample participants from the NSDUH. How would those evaluations of themselves affect their response to questions about addiction during their assessment? By the time people see me and they have an entirely different frame of reference. They may have had one (or several) near death experiences from overdosing on opioids. They may have become homeless and lost the support of their friends and family. They may have encountered a number of situations making the drug use problem very difficult to deny. The people receiving the REMS evaluation from their physicians will almost always be similar to the NSDUH sample. The implication is that these folks won't be "honest" with their physician, but the problem is much more than an honesty problem. Anyone with an addiction has lost their capacity to fully recognize the nature and severity of the problem. Their responses are based on a number of biased decision-making processes that continue the addiction. The primary care physician is in the impossible position of needing to be a lie detector with a person who may not feel like they are lying. It is another operation of the great unconscious but in this case one that is unrecognizably biased by addiction.
The response to opioids is the first clue that there may be a problem. People disposed to addiction have a striking response to opioids. The described an intense euphorigenic effect. In contrast to the usual ideas that opioids are sedating many will feel much more energetic and productive. A distinct feeling that a hoped for potential has finally been realized with the expected boost in confidence is often a third feature that is extremely reinforcing. These are generally the opioid response features that place a person at high risk for opioid addiction.
The unconscious aspects of drug addiction are described in a number of ways. Sellman describes it as compulsive drug seeking being initiated outside of consciousness. Koob talks about the process going from an initial process of an impulse control disorder involving positive reinforcement to compulsive activity that is driven by the negative reinforcement of avoiding withdrawal phenomena. Most people are not conscious of that process unless it it reviewed with them in detail. Another unconscious aspect of addiction is cravings. Cravings can vary from a spontaneous intense urge to use a drug to an urge associated with sensory phenomena that occurs after exposure to a drug cue like seeing people use the drug on television. Whether the craving is cue-induced or spontaneous they represent a drug induced change in a person's conscious state that can be present long after there has been exposure to a drug.
A risk management strategy to identify problems with opioid prescriptions needs to incorporate a strategy that takes these features into account. Information about limiting access to prescription opioids and destroying unused opioids is certainly a useful public health strategy but it does nothing for a person who has a strongly reinforcing reaction to the drug. At the minimum there needs to be education that the response to the drug is a key feature to identify addiction risk. Patients need to be educated about that as well as addictive behaviors and those anchor points need to be revisited at every physician visit where response to pain, addictive behavior, psychiatric comorbidity and functional capacity needs to be assessed. These are also the areas where the bulk of physician education needs to occur. There is also the issue of whether teaching primary care physicians is the best strategy to limit opioid overprescription. It may ultimately be the best strategy because the lessons learned could be applied to the overprescription of many drugs with similar dynamics like antibiotics, benzodiazepines, and stimulants. There is also the model of specialty referral to reduce the burden on primary care clinic. This model was popular in many states prior to the more widespread practice of prescribing opioids for chronic noncancer pain and it is the basis of the guideline for treating chronic neuropathic pain by the National Institute for Health and Care Excellence (NICE).
George Dawson, MD, DFAPA