The professional organizations recognized that patients with persistent pain who take opioids as prescribed on a consistent basis will inevitably develop tolerance and physical dependence, and will go into withdrawal if the medications are abruptly stopped.
Now, when it comes to all other substances of abuse, the occurrence of these phenomena are considered to be important aspects of what it means to be addicted to a substance. So, for example, if someone who had been consuming alcohol on a consistent basis over a period of time develops tolerance and physical dependence, and goes into withdrawal upon ceasing use of alcohol, most would consider such phenomena as indicative of alcoholism, or what’s now called an alcohol use disorder.2
However, the occurrence of these phenomena in a person who takes opioids for pain seems uniquely different when occurring in the context of a healthcare setting in which the opioids are prescribed by a provider and the medications are taken as prescribed for the pain of an identified health condition. Tolerance and physical dependence seem an inevitable result of taking the medications exactly as prescribed. As a result, tolerance, physical dependence, and the potential for withdrawal seem an artifact of the treatment, not of addiction. Because of this difference, the professional organizations cited above conventionally agreed to consider pain patients in such contexts as physically dependent, not addicted. Additionally, they re-defined the criteria for addiction to prescription opioids in this context as the occurrence of certain behavioral phenomena. Notably, they advocated that patients should be considered addicted to prescription opioids when patients exhibit behaviors indicative of having lost control over the use of the medications (e.g., no longer using them as prescribed) and/or using them despite harm to oneself (e.g., continuing to use high doses despite past accidental overdoses, or engaging in illegal activities in order to obtain opioid medications). These behaviors thus became, according to the conventional agreement by the professional organizations, the criteria for when a patient is addicted -- not tolerance, physical dependence and withdrawal.
Changes in the significance of physical dependence, tolerance and withdrawal
In the time since this distinction was made, providers and patients alike have also come to change the overall significance of tolerance, physical dependence and withdrawal, on the one hand, and addiction, on the other. Tolerance, physical dependence and the potential for withdrawal have come to be understood as largely benign artifacts of long-term opioid management. In other words, their occurrence is no longer to be considered alarming, but rather expected. Alarm came to be reserved only for when patients break opioid agreements by losing control over their use or continue to use opioids despite harm. In large measure, physical dependence and addiction thus became categorically different, the former became benign and expected, and the latter dangerous and alarming.
The history of this development in how we have come to think of addiction to opioid pain medications is documented in both the professional and popular literature. For instance, a second consensus statement3 between the American Academy of Pain Medicine, American Pain Society and the American Society of Addiction Medicine, published in 2001, asserted outright that physical dependence and tolerance are not symptoms of addiction when it comes to opioid pain medications when used for pain. Moreover, they added that their nature should be considered as benign. Comparing opioid-related physical dependence and tolerance to the physical dependence that can occur with high blood pressure medications and antidepressant medications, this consensus statement provided reassurance that physical dependence and tolerance are the “normal responses that often occur with the persistent use of certain medications.”
The concern, of course, about physical dependence and tolerance is that they are indications that the body (particularly the brain) has changed in response to persistent exposure to certain drugs and that this change can lead to addictive behaviors when the drugs are no longer readily accessible and are thus withdrawn from use. The comparison with high blood pressure and antidepressant medications makes it seem that such a possibility is rare – for who loses control of the use of high blood pressure and antidepressant medications when abrupt cessation of use occurs? This reassurance notwithstanding, the consensus statement does in all fairness acknowledge that losing control may be more likely with opioid pain medications, but subsequently doubled down with a bold, comforting position: “A patient who is physically dependent on opioids may sometimes continue to use these [sic opioid medications] despite resolution of pain only to avoid withdrawal. Such use does not necessarily reflect addiction.” Use of opioids to avoid withdrawal, even if pain is no longer present, is thus to be considered benign, because it is associated with the benign conditions of physical dependence, tolerance, and withdrawal.
The 2001 consensus statement by the American Academy of Pain Medicine, American Pain Society and the American Society of Addiction Medicine is not the only or last such reassurance that physical dependence, tolerance and withdrawal are largely benign and not to be associated with addiction. In 2006, leading figures in the fields of pain and addiction, including one who is now the head of the National Institute on Drug Abuse, similarly argued that tolerance, physical dependence and withdrawal upon cessation of use are categorically different from losing control over the use of opioids, or addiction. In their editorial published in American Journal of Psychiatry, they asserted that physical dependence and withdrawal are “expected pharmacological response[s]” and that they are “quite distinct from compulsive drug-seeking behavior.”4 They go on to argue that clinicians should refrain from becoming alarmed by the occurrence of tolerance, physical dependence and withdrawal and caution against stopping the use of opioids when they occur. In other words, they advocate that tolerance, physical dependence and withdrawal are expected and benign.
This sentiment has been adopted wholesale and it is now almost unquestioned by the professional healthcare community and the lay public. A quick internet search yields countless professional and patient-related hits providing reassuring explanations that tolerance, physical dependence and withdrawal are:
- different from addiction
- expected and benign artifacts of opioid treatment
- shouldn’t result in the cessation of opioid prescriptions or use.
The chair of the Council on Addiction for the American Psychiatric Association, Andrew Saxon, MD, cites these views even as late as last year in an interview on a popular patient-focused health internet site. He’s quoted as cautioning against confusing “physical dependence, which any patient would have if taking opioids repeatedly for chronic pain, with the full syndrome of addiction.”5
Do the facts match this conventional distinction?
In the time since these developments in our conceptual distinctions of physical dependence and addiction have occurred, we have also come to witness the development of epidemics of opioid-related addiction and accidental overdose.6 Initially, the problem of overdoses was predominantly related to prescription opioids, but in recent years deaths due to taking illegal forms of opioids, like heroin and illegally manufactured fentanyl, have come to modestly surpass deaths related to prescription opioids. Deaths due to both kinds of opioids now occur about 130 times each day.
Addiction to opioids is apt to account for the majority of these deaths. Estimates vary, but at any given time over the last few decades upwards of 20-30% of people taking prescription opioids exhibit behaviors of losing control and about 10% do so to the extent that they could be diagnosed with addiction.7 It’s also well-established that the vast majority of those who use illegal forms of opioids started their habit by taking prescription opioids.8
It’s important to recognize in this regard that some portion of those currently addicted, likely the majority, had started by taking prescription opioids for pain and for some period of time were taking them as prescribed on a repetitive basis, thus having become physically dependent prior to becoming addicted, assuming the conventionally determined definition of addiction described above.9, 10
Let’s therefore be specific. We know that most people who become addicted to opioids started the use of opioids by taking prescription opioids. In other words, few people who are now addicted came to their addiction by starting with heroin or illegal forms of fentanyl (though this minority percentage has been growing in recent years). Thus, the taking of opioids prescribed by a healthcare provider, presumably for an identified health condition, is the typical route taken by those who subsequently become addicted. It’s reasonable to acknowledge that for some period of time during the course of this trajectory a large percentage, if not the majority, of these patients were taking opioids as prescribed and becoming tolerant and physically dependent. While certainly an expected state of affairs for those who are taking opioids on a consistent basis over time, is it really accurate to say that physical dependence, tolerance, and the potential for withdrawal are benign?
At the very least, we should acknowledge that the development of tolerance and physical dependence in someone who is repetitively exposed to opioids by taking them as prescribed on a regular basis raises the risk for developing addiction. It would be hard to argue against the notion that duration of repetitive exposure to opioids, like any other addictive substance, is an independent risk factor for losing control over the use of opioids. Indeed, we’ve known that it is for some time.11, 12, 13
Problematic nature of physical dependence and tolerance
Physical dependence and tolerance to opioids have a neural substrate. In other words, they are indicators of changes to the brain that have occurred due to consistent exposure of the brain to opioids, such as what occurs when patients with identified health conditions take prescription opioids as directed on a consistent basis over time. Abrupt cessation of opioid use initiates withdrawal due to these changes to the brain.
Withdrawal from opioids is a highly distressing experience to which patients become correspondingly averse. The experience of withdrawal involves, among other things, compulsive urges to return to the use of opioids. Resumption of opioids readily comes to be experienced, at least in part, as relieving and welcoming, despite any degree of ambivalence that patients might have for remaining physically dependent on them. These experiences are directly related to the degree of physical dependence that consistent use of prescription opioids causes.
Clinicians in pain management commonly see patients who are so averse to the experience of opioid withdrawal that they resist or otherwise forego any discussions of changes to their treatment plan, even when it might be in their interest to do so. This aversion and resistance to withdrawal can occur without patients ever engaging in aberrant drug use behaviors that are indicative of loss of control or continued use despite harm. Rather, patients commonly express such aversion and resistance even when they take opioids exactly as prescribed. As such, they would be considered physically dependent, not addicted, and thus historically over the last few decades their physical dependence would be considered unproblematic. But, is it really?
Long-term duration of consistent opioid use, such as what we have seen in the common practice of long-term opioid management, leads to physical dependence that fosters an experience of opioid withdrawal, or even the potential for opioid withdrawal, as so aversive that it can come to independently maintain opioid use. This state of affairs behaviorally leads patients to become increasingly intolerant of opioid reduction discussions or treatment plans. In other words, it seems duration of physical dependence on opioids is directly correlated with difficulty in perceiving the possibility of a life of managing pain well without opioids.
Consider the problematic nature of this physical dependence. There are no aberrant behaviors indicative of impaired control, and yet this non-behaviorally aberrant dependence is not benign.
There are any number of patients who might fit this category of non-behaviorally aberrant dependency:
- Patients who adamantly maintain that opioids are helpful even though their pain remains at moderate to severe levels or remains disabling (“If my pain is as bad as it is now, just think what it would be like without opioids?”).
- Patients who remain fearfully avoidant of opioid reduction despite their own ambivalence or misgivings about being physically dependent on them.
- Patients who are referred to pain rehabilitation programs, which have long been known to have superior outcomes to opioid management, but forego recommendations to participate because one of the goals is to learn to self-manage pain and taper from opioid use.
- Patients with comorbid health conditions that are known to be problematic with the use of opioids, such as sleep apnea, who remain intolerant of opioid reduction or tapering discussions and thus remain on opioids.
- Patients with concomitant use of certain medications that are contraindicated with opioids, such as benzodiazepines, but who remain intolerant of opioid reduction or tapering discussions and thus remain on opioids.
- Patients who are so tolerant that they require doses that have come to be identified as having high risk for accidental overdose, but remain on opioids because the potential for reducing opioids is so averse.
All these patients may be taking opioids exactly as prescribed, adhering to their opioid agreements with their prescribing provider, and so would not be considered addicted, but rather physically dependent, and yet this type of dependency is problematic to varying degrees. In other words, their evident physical dependence, tolerance, and potential for withdrawal are not benign.
Moreover, clinically, what makes physical dependence with its potential for withdrawal especially problematic is that patients who develop these conditions increasingly lose their capacity for choice in whether to take opioids or not. Has any provider ever seen a long-term opioid management patient who is physically dependent and tolerant to opioids exhibit a causal, take-it-or-leave attitude to the use of opioids? Rather, what clinicians experience are patients who are significantly emotionally invested in maintaining their use, fearfully avoidant of reducing opioids to the point of being averse to the idea, and insistent that a life without opioids would be nothing but a life of intolerable pain and suffering, despite evidence to the contrary. Discussions with such patients about the need to taper or reduce opioids are also commonly wrought with shame, tears, anger, accusations, or defensiveness.
Patients in this state of affairs might be considered psychologically dependent. The choice of whether to remain on opioids is no longer the result of an entirely rationally derived cost-benefit ratio. Because the potential for opioid withdrawal that comes along with being physically dependent is so aversive, the possibility of coming to manage pain well without the use of opioids, which is typically seen as a good thing, is perceived by the patient as threatening. As so often occurs in the consulting room with such patients, it is cause for either fearful or angry avoidance. As such, patients no longer possess full capacity for reasoned consideration of their choices, but are rather automatically reacting to threat. In other words, physical dependence leads to diminished capacity for self-observant, reflective, rational choice.
From this light, even in such cases where there are no aberrant behaviors indicative of addiction, how did the field of pain management ever come to hold that physical dependence, tolerance, and the potential for withdrawal are unproblematic? No doubt, non-normal neural substrate changes underlie this physical dependency and so we could point to their non-normal nature as evidence that this state of affairs is problematic, but we really don’t have to do so in order to see that physical dependence, tolerance and the potential for withdrawal are not benign. As pain management providers and as loved ones of long-term opioid management patients, we can see it everyday in the people for whom we have been charged to care. Their physical dependence manifests as diminished capacity for reasoned consideration to choose whether to be on opioids or not. Indeed, in the highly physically dependent patient who is subsequently highly averse to the potential for opioid withdrawal, a loss ensues in one’s ability to even perceive that a life with chronic pain is possible in any other way but with opioids.14
Precursor to addiction or an aspect of addiction?
As physical dependence increasingly leads to the loss of the ability to perceive the possibility of managing pain well without opioids, the ability of long-term opioid management patients to make entirely rational decisions about whether to remain on or reduce opioids becomes diminished. This statement is not a moral judgment, but an observation about what it is like to be physically dependent on a substance, such as an opioid medication. The potential for withdrawal is perceived as so averse that fear and angry avoidance reigns over any misgivings that might otherwise lead one to consider their use in a more rational manner. Considered decision-making, whether in the office between provider and patient, or inside the head of the patient as internal conflict or ambivalence, can readily and quickly be shut down.
This diminished capacity for reasoned consideration, or what mental health providers call insight, is an essential aspect of compulsive or aberrant behaviors indicative of addiction. For without such capacity for reasoned consideration, urges to use, when withdrawal starts to occur, will become increasingly unstoppable. Insight, in other words, acts as a break on the urge to use, allowing for some degree of reasoned consideration as to whether to take the medication or not.
For this reason, distress tolerance is commonly taught and practiced in substance use disorder (i.e., chemical dependency) treatment. Increasing distress tolerance is one way to foster greater abilities to observe and consider one’s potential responses to aversive stimuli, such as withdrawal and the subsequent urges to use. It allows for greater intentionality in choosing a response to these stimuli, as opposed to immediately and automatically reacting with using behaviors in response to an urge to use without ever thinking about other potential behavioral options.
As we’ve seen, however, patients with an extended duration of long-term opioid use and increasing tolerance to opioids, become increasingly averse to withdrawal and subsequently their capacity for tolerance to aversive stimuli diminishes. As long as access to opioids remain uninterrupted, they experience no reason to test this diminished capacity to aversive stimuli because they do not go into withdrawal. This is how we might connect the dots between the decades-long practice of long-term opioid management and the opioid epidemics of addiction and accidental overdose.
Specifically, as a field, we have been managing a generation of long-term opioid patients who are so physically dependent and subsequently so averse to opioid withdrawal that the only thing that keeps them from engaging in aberrant behaviors of uncontrolled use is that they do not go into withdrawal because they maintain regular access to opioids by means of their healthcare providers. In other words, if prescriptions of opioids abruptly ceased, even if for inadvertent reasons, such as a job termination with subsequent loss of health insurance, they’d likely exhibit loss of control in reaction to the urges to use that accompanies their withdrawal. They’d likely exhibit such loss of control simply because of their diminished capacity to tolerate the aversive nature of withdrawal. They no longer have full capacity to engage in reasoned consideration of their options in response to the stimuli and so automatically react with using behaviors indicative of addiction. Their addiction thus becomes apparent, having previously been lying hidden (or misunderstood) in what had heretofore been thought of as something categorically different -- physical dependence.
Thus, the central question here is whether physical dependence and addiction are two distinct categories or aspects of each other? I argue that the field of pain management made a mistake in conventionally agreeing to consider physical dependence on prescription opioids as benign and distinct from opioid addiction. Rather, they are aspects of the same thing and they are not benign, but alarming.
The epidemics of opioid addiction and accidental overdose that has become manifest in our society reveal that the pain-related professional organizations’ re-definition of addiction and its categorical distinction between physical dependence and addiction are misguided. It led to false assurance that physical dependence, tolerance and the potential for withdrawal are largely benign and as a result the healthcare system has unwittingly led the opioid management patient down the garden path, a garden that in actuality is full of thorns. In other words, by re-defining addiction solely along behavioral lines, we have failed to recognize the not-so-benign nature of how the long-term use of opioids lays the physiological underpinnings that lead to the manifested behaviors of addiction. Physical dependence is not categorically different from addiction, but rather it is a related aspect of the same phenomenon.
1. American Academy of Pain Medicine and the American Pain Society. (1997). The use of opioids for the treatment of chronic pain: A consensus statement from the American Academy of Pain Medicine and the American Pain Society. Clinical Journal of Pain, 13, 6-8.
2. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Association.
3. American Academy of Pain Medicine, American Pain Society & American Society of Addiction Medicine. (2001). Definitions related to the use of opioids for the treatment of pain: Consensus statement of the American Academy of Pain Medicine, American Pain Society & American Society of Addiction Medicine. Wisconsin Medical Journal, 100(5), 28-29.
4. O’Brien, C. P., Volkow, N., & Li, T-K. (2006). What’s in a word? Addiction versus dependence in the DSM-V. American Journal of Psychiatry, 163(5), 764-765.
5. Stephens, S. Opioids: Key differences between physical dependence and addiction. December 27, 2008; Updated August 9, 2018. Health Central. Retrieved 2-23-2019.
6. Center for Disease Control and Prevention. (December 19, 2018). Understanding the epidemic. Retrieved 2-24-2019.
7. National Institute on Drug Abuse. (January 2019). Opioid overdose crisis. Retrieved 2-24-2019.
8. Cicero, T. J., Ellis, M. S., Surratt, S. L., & Kurtz, S. P. (2014). The changing face of heroin use in the United States: A retrospective analysis of the past 50 years. JAMA Psychiatry 71(7), 821-826. doi: 10.1001/jamapsychiatry.2014.366
9. Fibbi, M. Silva, K., Johnson, K. Langer, D., & Lankenau, S. E. (2012). Denial of prescription opioids among young adults with histories of opioid misuse. Pain Medicine, 12(18), 1040-1048. doi: 10.1111/j.1526-4637.2012.01439.x
10. Han, B., Compton, W. M., Bianco, C., Crane, E., Lee, J., & Jones, C. M. (2017). Prescription use, misuse, and use disorders in U. S. adults: 2015 National Survey on Drug Use and Health. Annals of Internal Medicine, 167(5), 293-301. doi: 10.7326/M17-0865.
11. Ahmed, S. H., Koob, G. F. (1998) Transition from moderate to excessive drug intake: Change in hedonic set point. Science, 282, 298-300.
12. Koob, G. F., Ahmed, S. H., Boutrel, B., Chen, S. A., Kenny, P. J., Markou, A., O’Dell, L. E., Paron, L. H., & Sanna, P. P. (2004). Neurobiological mechanisms in the transition from drug use to drug abuse. Neuroscience & Biobehavioral Reviews, 27(8), 739-749.
13. Volkow, N. & Li, T.–K. (2004). Drug addiction: The neurobiology of behavior gone awry. Nature Reviews: Neuroscience, 5, 963-970.
14. Another interesting problem, which we won’t discuss here, is when providers come to believe that these experiences of physically dependent patients are objectively true – in other words, the providers too come to believe that pain without opioids will inevitably lead to intolerable suffering and so come to believe that opioids are necessary for the well-being of their patients. Providers can thus come to align themselves with these experiences of patients, and subsequently become resistant to changes in the field, such as new opioid prescribing guidelines that recommend reducing and/or tapering opioids, in the belief that they are advocating for the rights of their patients.
Date of publication: 10-5-2019
Date of last modification: 10-5-2019