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Payers Tue, 31 Jan 2023 11:24:47 +0000 Joomla! - Open Source Content Management en-gb Continued Use Despite Harm: The Under-Utilized Criterion for an Opioid Use Disorder Diagnosis

Over the last few years, I have argued that we need to rethink the nature of opioid use disorder in the population of people who take opioids as prescribed for moderate-to-severe persistent pain. I’ve done so in various formats, including in presentations as well as here at the Institute for Chronic Pain, in both web pages (Should the Definition of Opioid Addiction Change? and Opioid Dependency & the Intolerability of Pain) and blog posts (The Central Dilemma in the Opioid Management Debate and Dreaded or Embraced? Opioid Tapering in Chronic Pain Management). 

I do so because I think that the fields of both pain management and addiction are overly focused on loss of control as the primary indicator of when a person on long-term opioids for pain management crosses the line into the problematic state of an opioid use disorder (OUD). The argument these fields tend to use goes something like the following: 

  • Physiological dependence on opioids, in the population of people who use prescription opioids on a daily basis for the management of pain, is largely considered as a condition that is both expected and benign when compared with the condition of an OUD. Physiological dependence, in other words, doesn’t necessarily rise to the level of alarm unless someone on such medications begins to evidence a loss of control over their use. 
  • Loss of control is largely considered a compulsive condition, which is neither expected nor benign, since it leads to distress and/or functional impairment, or even death by means of accidental overdose. 
    • Examples of loss of control tend to be readily observable: repetitive self-escalation of the use of opioids, leading to early refill requests; obtaining opioids from multiple providers at the same time or from friends or relatives or other illegal sources; use of opioids that aren’t prescribed; etc. 
  • At the current time, we tend to reserve the term “misuse” to refer to those instances of use which fail to be in accordance with how the medication is prescribed1; when done repetitively, misuse can cross the line into compulsive use, which is indicative of loss of control, and thus come to exhibit some degree of an OUD. 
  • Repetitive misuse and loss of control tend to go hand in hand and are seen as in contrast with those who may be physiologically dependent, but take opioids as prescribed. 

This line of reasoning has taken hold in the fields of pain management and addiction. In common practice, what it means is that the typical Image by Ahmed Zayan courtesy of Unsplash litmus test for whether someone on prescribed opioids for pain is addicted or not is whether they are taking their medications as prescribed or not. If they are taking their medications as prescribed, they may be physiologically dependent, but not addicted. If not, they are identified as both physiological dependent and addicted, since they have crossed the line into compulsive use behaviors and as such have lost control of their use. 

Misuse and loss of control are admittedly the clearest indicators of problematic use of prescription opioids. Typical examples, as already noted, tend to be readily observable. There’s relatively little doubt, for instance, when an opioid that isn’t prescribed shows up on a urine drug screen. Nonetheless, the fields of pain management and addiction have historically indicated an additional criterion for OUD, which is continued use despite harm.2, 3 This criterion tends to get short shrift in clinical practice. Perhaps, it is because it is not as clearly recognizable as what has come to be recognized as loss of control – the misuse of opioids or taking them in an unprescribed manner. Perhaps too, it is because it can occur in the absence of such misuse. In other words, continued use despite harm can occur when patients take opioids exactly as prescribed, and as such they aren’t as readily identified as addicted. 

Moreover, another reason that those in clinical practice tend to fail to recognize continued use despite harm is that the matter can be confused with patient-reported high pain levels and what constitutes a reasonable response to such pain levels. To put succinctly, it can be difficult to differentiate between continued use despite harm and appropriate medical decision-making in response to moderate-to-severe pain.

Let’s explain each of these two difficult-to-recognize aspects of opioid use disorder one at a time.

Addiction to opioids when taking opioids as prescribed

As the phrase continued use despite harm suggests, the criterion of OUD under consideration occurs when a patient on prescription opioids for pain management insists on their continued use even if it places the patient in danger, such as risk of accidental overdose or exacerbating a co-occurring life-threatening condition. 

The criterion is most clear when it occurs in the context of illegal use of opioids, such as those that are bought off the streets or other non-medical sources. The problematic nature of insisting on the use of opioids when having no knowledge or assurance of their true nature is clear. In some ways, it is a variant of impaired control: you use what you are told are hydrocodone pills, for instance, but you actually have no knowledge of whether they are truly hydrocodone; they may be hydrocodone, but they might also be illegally manufactured fentanyl; as such, the use of these pills place you at considerable risk of harm (e.g., accidental overdose, since fentanyl is exponentially more potent); a more reasonable decision in response to this lack of knowledge would be to forgo their use; one who continues to insist on their use is acting with impaired control. 

But what of the use of this criterion for OUD in a population of people who are taking legally obtained, prescribed opioids for the management of pain?

Say, for example, a person who takes high-dose daily opioids for moderate-to-severe persistent pain also has severe sleep apnea. He reports that he is intolerant to the use of a C-PAP and so his continued use of high-dose opioids places him at significant risk of accidental overdose. His healthcare providers have cautioned against continued use of opioids, especially at his current high dose levels, and have gone so far as to encourage him to reduce his current opioid dose, but he remains adamantly against it and refuses. 

Now, to be clear in our example, the patient is using opioids as prescribed and he takes only those opioids prescribed to him. As such, he is not misusing them and so most providers and patients in this scenario don’t tend to consider use of prescription opioids of this kind as meeting criterion for having lost control. As such, most wouldn’t consider him to have an OUD.

Nonetheless, it is a problematic scenario. He is refusing, so to speak, to come off the ledge of a dangerous precipice. He might die with hisImage by Loic Leray courtesy of Unsplash current use, but nevertheless refuses to change his current use. 

Suppose further that his healthcare providers have cautioned him against continued use at the high dosing schedule and have supportively encouraged him to reduce many times. Maybe his spouse or family have joined in on the encouragement to reduce his dose. He subsequently knows that his continued use may cause him harm, if not death. Were it not for the fact that the substance in question is a prescribed opioid for pain, it would be clear to all that he suffers from impaired use. For instance, suppose in this example the substance wasn’t opioids but alcohol: he continued to consume alcohol after having been told in similar circumstances and by similar people that a pre-existing liver condition is increasingly made worse and so continued use poses considerable risk of harm, if not death. The two instances of impaired control are essentially similar. It’s just that when opioids are used in these ways under the auspices of a prescribing provider it seems to cloud the recognition of an OUD.

This example is not an uncommon scenario in the field of pain management. Day-to-day clinical experience is replete with additional examples of those who continue to insist on using opioids in high risk scenarios: 

  • patients who take exceptionally high doses because of the tolerance that has developed over years of taking opioids on a daily basis as prescribed
  • patients on moderate (or high) doses of opioids who have taken them for years as prescribed and are increasing in age, thus their current dose is increasingly dangerous with each passing year
  • patients on moderate (or high) doses who also take benzodiazepine medications or sedative hypnotic medications
  • obese patients on moderate (or high) doses, with or without sleep apnea, who also take such latter medications
  • elderly patients on opioids who continue to use opioids following a fall or following the onset of cognitive impairment as a side effect of opioids
  • patients with a history of addiction who take long-term, daily opioids as prescribed
  • patients who continue to use opioids following an accidental overdose.

The list could go on.

It’s rare for providers in actual clinical practice of pain management to recognize these behaviors as an OUD.

Through the course of my career, I have found it uncommon among my addiction medicine colleagues as well. Consults related to patients like those described above tend to come back that the patients are using their medication as prescribed and so do not have an OUD. At best, the consult comes back with a recommendation to the prescribing provider to reduce the opioids, but even this helpful recommendation obscurs the fact that it is the patient, not the provider, who is refusing to reduce their opioid dosing and thereby their risk.

Succinctly, the fields of pain management and addiction medicine need to change their perspective on the criterion that we ourselves have advocated for using when diagnosing an OUD. Continued use despite harm can occur even when patients are using opioids as prescribed.

These examples of continued use despite harm are indicative of impaired control over the use of opioids. It is because of the addictive nature of opioids that such patients insist on their continued use under high-risk circumstances.

Suppose, for example, someone with a severe depression develops serotonin syndrome due to the use of antidepressants and the healthcare providers’ recommendation is to stop the use of the medications. We’d be hard pressed to imagine a scenario in which the patient becomes so sensitive and threatened by the recommendation that he or she becomes argumentative and insistent on the continued use of the medications that cause such risk. While all things are possible, such a scenario is not common. In most scenarios of this kind, the patient is open to the recommendation to reduce the use of antidepressants and open to pursuing alternative therapies for depression. 

It is much more common, though, in the population of those with persistent pain who have been taking moderate to high daily doses of opioids despite the above risk of adverse events.

Suppose, to take another example, the long-term use of a proton pump inhibitor is now thought to be contributing to certain health risks and the recommendation is to stop the use of the medication and seek alternatives. It would be uncommon for patients in this scenario to become argumentatively insistent on its continued use despite the associated risks.

Again, it is common in the population of those taking long-term opioids for pain with concomitant risk factors.

Suppose, to take one last example, someone develops a GI bleed from the long-term use of an anti-inflammatory for moderate-to-severe arthritis pain and as a consequence the recommendation from healthcare providers is to discontinue the use of an anti-inflammatory and seek alternative therapies for the management of pain. While it may be common to have misgivings in this scenario, it would be uncommon for individuals to become so threatened by the loss of the medication that they are argumentatively insistent on its continued use despite the GI bleed. 

As has been mentioned, it is fairly common in similar high-risk scenarios when taking long-term opioids.

The difference, of course, between all these examples and that of opioids is that opioids are highly addictive. With repetitive exposure to addictive substances, brain changes occur that lead to compulsive use even in high risk scenarios. In the absence of such brain changes, people maintain the ability to control their behavior, making more or less rational decisions, in response to risk. Antidepressants, proton pump inhibitors, and anti-inflammatories simply do not foster such changes to the brain and so these capacities for rational decision-making are maintained. Opioids, however, do foster such changes to the brain, thus leading to impaired decision-making, or control, and continued use despite associated risks is the result.

Continued use despite harm & confusion with appropriate responses to high pain levels

Patients who insist on the continued use of opioids under conditions of risk to their life commonly maintain that pain relief is more important than life itself. They argue that without pain relief their life would be insufferable and so, when compared to a life of intolerable pain, the risk of catastrophic events such as death through accidental overdose or relapse of a prior addiction (for those on opioids with a prior history of addiction) is preferable.

On countless occasions in clinical encounters or public forums, such as in public policy debates, patients on long-term opioids, who have a history of taking opioids exactly as prescribed, maintain such sentiments: life with their level of pain wouldn’t be worth living were it not for opioid medication management. In other words, opioids are literally their lifeline.

Indeed, such sentiments are often perceived as immediately and obviously true: living a life of moderate-to-severe daily pain seems an intolerable prospect without opioids, and so their use along with their associated risks, seems the preferable option. Any expression of doubt by others is met with affront and accusations of stigmatizing those who have the unchosen life circumstances of living with moderate-to-severe persistent pain. The common litmus test for understanding is living under such circumstances or not: “If you had my level of pain, you’d understand!” The litmus test shuts down the possibility of managing pain well without opioids.

To make clear, the implied corollary to this assertion is that managing moderate-to-severe pain is impossible without the use of opioids. Some pain, in other words, simply requires opioids. There is no other choice between the use of opioids and intolerable pain and suffering. (“You think I like taking opioids?!? There’s nothing I’d like better than to not have to take them!”) Self-management of certain pain levels seems just not possible.

Healthcare providers who prescribe long-term opioids often make a similar calculation: reduction of pain with opioids is a greater value than any of the afore-mentioned catastrophic adverse events. Moreover, such providers typically never think twice about the calculation, perceiving it similarly as their pain patients – the risk-benefit ratio seems to immediately and obviously fall on the side of the ledger involving use of opioids. (See, How Important is Pain Reduction with Opioids?)

Indeed, the reader of this article may have been saying something similar when I used the analogy to someone who continues to use alcohol despite a life-threatening liver condition. It’s easy to argue that the two scenarios are different because the patient using opioids is using opioids for pain, while the patient using alcohol is not using alcohol for a legitimate medical condition. In this context, we might observe the almost countless frequency of people who use alcohol despite high risks because they are using alcohol to medicate latent depression or past trauma. The reader might counter that while depression and trauma are legitimate health conditions, the use of alcohol to medicate them are not legitimate medical responses to them. True, but that is exactly what is at question: Is the use of opioids despite the risk of catastrophic harm, such as death or the exacerbation of a pre-existing addiction, an appropriate response to moderate-to-severe pain?

With the empathy and compassion of those who care for people with the unchosen life circumstance of living with moderate-to-severe pain, it is time to question whether this risk-benefit calculation is warranted. We know, for instance, that most people in the general population with moderate-to-severe pain do not take opioids for pain.4, 5 This fact is the norm. The norm is not the continued use of opioids despite risk of harm. 

Indeed, it is time to even take it a step further: the unquestioning, steadfast belief that some pain is simply so great that no other choice is possible but for to take opioids at the risk to life is indicative of a problematic state of addiction, even if the use of opioids is exactly as prescribed. The perception that pain is so severe that it is prima facie intolerable without opioids in people taking daily opioids for years is a function of neuroplastic changes to the brain induced by repetitive exposure to opioids. The personal affront with which other peoples’ doubts of these unquestioning perceptions are met is the shame-based defensiveness that so often accompanies addiction. When those suffering from an addiction are initially approached about their addiction by others, the common response is denial and affront.

Again, most people with moderate-to-severe persistent pain do not take opioids for pain, let alone do so despite life-threatening risks. They do not perceive moderate-to-severe pain as insufferably intolerable. Without repetitive exposure to opioids, they haven’t undergone neuroplastic changes to their brains that influence their perceptions and abilities to make rational decisions in response to pain. They do not feel compelled to take opioids in response to moderate-to-severe pain despite life-threatening risks. In other words, they do not have an OUD. 

Continued use despite harm has long been advocated for use in the identification of those with an OUD by the fields of pain management and addiction. It has, however, been long under-utilized in the population of people who take long-term opioids as prescribed for the management of persistent pain. For the welfare of those for whom we care in these fields, it is time for this under-utilization to change.


1. Volkow, N. D., Jones, E. B., Einstein, E. B., & Wargo, E. M. (2019). Prevention and treatment of opioid misuse and addiction: A review. JAMA Psychiatry, 76(2), 208-216. doi: 10.1001/jamapsychiatry.2018.3126

2. American Academy of Pain Medicine and the American Pain Society. (1997). The use of opioids for the treatment of chronic pain: A consensus statement. Clinical Journal of Pain, 13, 6-8.

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. Nahin, R. L., Sayer, B., Stussman, B. J., & Feinberg, T. M. (2019). Eighteen-year trends in the prevalence of, and health care use for, non cancer pain in the United States: Data from the Medical Expenditure Survey. Journal of Pain, 20(7), P796-809. doi: 10.1016/j.pain.2019.01.003

5. Toblin, R. L., Mck, K. A., Perveen, G., & Paulozzi, L. J. (2011). A population-baed survey of chronic pain and its treatment with prescription drugs. Pain, 152, 1249-1255.

Date of publication: 10-17-2022

Date of last modification: 10-17-2022

About the author: Murray J. McAllister, PsyD, is a pain psychologist and consults to clinics and health systems on improving pain care. He is the founder and editor of the Institute for Chronic Pain.

]]> (Murray J. McAllister, PsyD) Opioids Sun, 16 Oct 2022 15:01:47 +0000
Should the Definition of Opioid Addiction Change?

Twenty some odd years ago, the American Academy of Pain Medicine and the American Pain Society, two large pain-related professional organizations, teamed up to agree upon what it means to have both chronic pain and be addicted to opioid pain medications at the same time.1 They did it because addiction to opioid medications when patients are prescribed them for legitimate health reasons seems different than addiction to other substances like alcohol, cannabis, cocaine, or even illegally obtained opioid medications when not used for pain. The difference involves the phenomena of tolerance, physical dependence, and withdrawal, which in part serve as criteria for the diagnosis of addiction when it comes to all other substances.

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 Photo by Mitchell Hollander Courtesy of Unsplashconsensus 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 suchPhoto by Steve Johnson Courtesy of Unsplash 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

]]> (Murray J. McAllister, PsyD) Chronic Pain Rehabilitation Sat, 05 Oct 2019 17:59:01 +0000
Opioid Dependance and Addiction Opioid Addiction

Opioid, or narcotic, pain medications are beneficial in a number of ways. Terminal cancer patients, for instance, benefit from their use. The short-term use of opioid pain medications is beneficial, especially while recovering from an acute injury or a surgery. However, the long-term use of opioid medications for chronic, noncancer, pain remains controversial. While a number of issues contribute to this controversy, the main reason for the controversy is addiction. Opioid pain medications are addictive.

This controversy makes opioid pain medications a highly sensitive issue for patients who take them.

In the 1990’s and early 2000’s, it was common for some healthcare providers to believe that addiction to opioid pain medications didn’t necessarily occur, especially if patients appropriately used their medications to manage pain. The belief was that as long as patients used the medications for pain (as opposed to some other reason, such as to get high) they simply wouldn’t get addicted. It was as if to say that as long as a patient has pain and as long as the intention is to take the medications for pain, then these two factors would disqualify someone from getting addicted. Patients too tended to embrace this sentiment. It was, of course, hugely reassuring. Patients could take the medications and healthcare providers could prescribe them without any alarming concerns.

It’s now well-known that people can have chronic pain and get addicted to opioid pain medications at the same time. It is not an either-or issue. It’s also known that addiction can occur in unintended ways. Intentions don’t really matter. No one ever intends on becoming addicted to anything, opioid pain medications included. Addiction to opioid pain medications can happen, even if patients set out to take them only for pain. So, patients should be concerned about it.

The following attempts to set aside the sensitivity of the issue of addiction and simply explain key concepts of addiction when it comes to the use of opioid pain medications, especially in the context of their long-term use for a chronic pain condition. The key concepts are physiological dependence, psychological dependence, and addiction.

Physiological dependence

When taking opioid medications on a daily basis over a long period of time, patients become physiologically dependent. The body becomes adjusted to having the medication in its system. As a result, two things happen. First, patients become tolerant to the medication. Tolerance is when the body becomes adjusted to the use of opioid medications and as a result the medications lose their effectiveness over time. Second, patients experience withdrawal symptoms if the medication is abruptly stopped. All patients develop physiological dependence when taking opioid medications over time.

Patients frequently mistake physiological dependence for addiction. It’s understandable. With any other drug, people consider physiological dependence as part and parcel of addiction. Take, for example, an individual who experiences tolerance and withdrawal from the use of alcohol. Most would consider the individual an alcoholic. It’s understandable, then, that most would consider the chronic pain patient an addict when they develop tolerance to their medication and experience withdrawal if they abruptly stopped the use of the medication.

However, the use of opioid medications for chronic pain is a unique situation, when compared to the use of other addictive drugs, like alcohol. When people use alcohol (or any of the illegal drugs) to the point of tolerance and withdrawal, most people would consider that they are doing something wrong. When chronic pain patients use opioid medications on a daily basis to the point of tolerance and withdrawal, they are doing just what their healthcare provider told them to do. If patients use their medications exactly as prescribed, they inevitably become tolerant and could experience withdrawal. Notice that they are not doing anything wrong. It’s what makes the situation unique from the use of other addictive drugs.

The American Academy of Pain Medicine and the American Pain Society noticed this difference too. A number of years ago, they decided to team up and define a difference between physiological dependence and addiction. They defined addiction to opioid medications using two criteria: a loss of control over the use of the medication or continued use of the medication despite real or potential harm.1 These criteria are more fully explored in the section on addiction.

While its important to acknowledge the difference between physiological dependence and addiction, it’s also important to acknowledge that tolerance and withdrawal are not benign issues. Even if they are not addiction, many patients are rightfully concerned about them.

Tolerance makes it unfeasible to continue to use opioid medications for pain on an indefinite basis. Patients and their healthcare providers commonly do not consider this problem until it is too late. Patients who have been on opioid medications for a few years become tolerant to even the highest doses of opioid medications. The medications no longer work and yet the patients have the rest of their lives to live. They may need opioid medications for other injuries or surgeries in the future and yet they are now tolerant to the medications. It is a problem for many patients.

The possibility of withdrawal is also a concern for many patients. They simply don’t like their dependency on the medication or their dependency on the healthcare provider who prescribes them. There might be many situations in which patients inadvertently do not have access to their medication or to their provider. This dependency produces a sense of vulnerability. Many patients just don’t like this sense of dependency and vulnerability.

Psychological dependence

When patients use opioid pain medications on a long-term basis, they tend to develop subtle yet strongly held beliefs that lead to a loss of confidence in their own abilities to cope with pain. As such, they come to believe that it is impossible to successfully manage pain without the use of opioid medications. Moreover, they become unwilling to entertain alternative options to their use. As a consequence, patients come to overly rely on the medications long after they are no longer helpful. In other words, opioid medications foster psychological dependence.

This issue is difficult to talk about. It’s difficult because these beliefs are subtle and don’t really come to the foreground unless actually named. It’s also difficult to talk about because it’s a sensitive issue. It can evoke strong emotional reactions.

Patients who are psychologically dependent on opioids are often intolerant of the notion that it is possible to manage pain well without opioids. They might see it as ridiculous. When a healthcare provider raises the notion, they take it that the healthcare provider is incompetent. At other times, patients see it as evidence that the healthcare provider doesn’t understand what it’s like to have chronic pain. They can also see the notion that it is possible to manage pain well without opioids as invalidating the legitimacy of their pain. In any of these ways, patients can get dismissive or angry. As described, it is a sensitive issue. However, the sensitivity is also indicative of psychological dependence.

Patients who are psychologically dependent on opioid medications are often unwilling to entertain different treatments for their pain, even when those treatments might be more effective. For example, numerous studies and reviews2, 3 have shown that chronic pain rehabilitation programs are more effective than long-term use of opioid medications. The psychologically dependent patient tends to forego recommendations to participate in such programs, even though they are more effective. It’s hard to come up with any analogous situation in healthcare. Cancer patients typically don’t insist on using one type of chemotherapy drug when their oncologists recommend using a more effective type. Most patients wouldn’t insist on using an antibiotic that has been consistently shown to be less effective than another medication or treatment. This kind of situation, though, commonly happens when it comes to the use of opioid medications for chronic pain. The difference is that opioid medications have the capacity to foster psychological dependence in the patients who take them. As such, they insist on using opioid medications even when there are other, more effective options for the management of pain.

Patients who are psychologically dependent on opioids rely on the medications long after they cease to be helpful. They tend to demonstrate tolerance to the medication, describing their pain as severe despite taking high doses of opioids. They may also remain disabled by pain, despite the use of opioid medications. Nonetheless, they swear that the medications are helpful. This disconnect between their subjective belief that the medications are helpful and the objective evidence of their reports of continued high levels of pain and disability is an indication of psychological dependence.

It bears remembering that most people with chronic pain do not manage their pain with opioid medications. In an epidemiological study, Toblin, et al., found that a quarter of the population has chronic pain; but among people with chronic pain, they found only 15% using prescription opioids to manage their pain.4 Now, it might be argued that the majority of people with chronic pain should be on opioids and that in fact it’s inhumane that in this day and age the majority of people with chronic pain are still being denied the use of such medications. But, that’s not what these researchers found when they asked people with chronic pain in the study. They found that the vast majority – 80% of them – were satisfied with their pain management. So, it’s true that the majority of patients with chronic pain manage their pain without opioid medications.

Patients who are psychologically dependent on opioid medications tend to believe that it is impossible. They are sensitive to the notion that it is in fact possible and can get emotional when it is brought up. They lack an openness to treatment options that might be more effective than opioid medications. Lastly, they maintain the belief that the medications are helpful and necessary despite their continued reports of high levels of pain and despite the fact that they remain disabled.


As indicated earlier, the conventional definition of addiction to opioid medications has two criteria, when their use is in the context of chronic pain management.

  • Loss of control over use of the medication
  • Continued use despite harm

Loss of control occurs when patients do not use the medications as prescribed or in accordance with the agreement that they make with their healthcare providers. In other words, they do not control their use of the medications. Continued use despite harm occurs when patients continue to use the medications even though their use is harming their relationships with others or putting them at physical or legal risk. When patients demonstrate a pattern of behaviors that are indicative of either of these criteria or both, healthcare providers diagnose addiction.

Some examples of a loss of control are the following behaviors:

  • Taking more of the medication than prescribed
  • Early refill requests
  • Multiple reports of lost or stolen medications
  • Repetitive emergency room visits to obtain medications
  • Use of multiple healthcare providers at the same time to obtain medications
  • Use of a friend’s or relative’s medications
  • Breaking the long-acting nature of a medication and ingesting it
  • Buying medications from people who are not healthcare providers
  • Buying medications off the internet

Some of these behaviors are more significant than others. Most healthcare providers would require a pattern of behaviors for the less significant ones. For example, a patient may have a legitimate reason for an early refill request. One instance of this behavior may not be concerning. However, a pattern of such requests almost every month for a number of months does become concerning. Healthcare providers tend to consider such a pattern as indicative of addiction. Other behaviors on the list are more significant. Most healthcare providers become concerned about addiction after even one instance of some of these behaviors. For examples, there are no legitimate reasons to break the long-acting nature of a medication or to buy medications off the streets. When healthcare providers learn about a patient engaged in these types of behaviors, even if it was only once, it is concerning. In fact, it is an indicator of addiction to opioid medications.

Some examples of continued use despite harm are the following behaviors.

  • Pressuring, manipulating, belittling, or threatening a healthcare provider into prescribing opioids
  • Refusing to participate in therapies other than opioid medication management
  • Firing an otherwise competent healthcare provider because of disagreements over whether to prescribe opioid medications
  • Continued use of opioid medications despite expressed concerns about addiction from friends, relatives and healthcare providers
  • Using such high doses of medications that the patient becomes incoherent or falls asleep while engaged in activities
  • Using a false identity to obtain opioid medications
  • Stealing medications from others
  • Altering a prescription

These behaviors also exhibit a loss of control, but the emphasis is on the fact that they are done despite some type of harm to the patient. The loss of control has not been perceived as ‘a wake-up call’ and so the behaviors have crossed a threshold of jeopardizing the patient in some manner. Some of these behaviors harm the relationships that the patient has – relationships with healthcare providers, friends or relatives. Some of these behaviors place the patient or others at risk of physical harm. An example is using medications at such high doses that a patient falls asleep while engaged in a wakeful activity or otherwise is unable to fully track or pay attention to the activity. Other behaviors place the patient at risk of legal harm. Examples are using a false identity or stealing medications or altering a prescription. These activities are, of course, illegal and yet the addicted patient might still do them. In all these examples, the loss of control is evident to others but the patient might not see it or might make excuses for it because obtaining the medication has become more important than the risks. All these behaviors are indicative of addiction.

How often does addiction occur in chronic pain patients?

In the context of chronic pain management, addiction is a significant problem. In their literature review, Hojsted & Sjogren5 cited studies that showed rates of a wide range of addictive behaviors, varying from 0% to 50%. In their meta-analysis published in the same year, Martell, et al.,6 found that 5-24% of patients on opioid pain medications demonstrate the above-mentioned problematic behaviors, depending on the behavior.

In more recent studies, Hojsted, et al.,7 used two different methods for diagnosing addiction. Depending on the method, they found either 14.4% or 19.3% of chronic pain patients meeting criteria for addiction to opioid medications. Within the context of a larger study, Skurtveit, et al.,8 had 686 chronic pain patients who regularly used opioid medications and they identified 191 of them as engaged in problematic behaviors indicative of addiction. The percentage is about 28%. In their study of people prescribed opioids across multiple Western countries, Morley, et al.,9 found a range of misuse and abuse from 8 to 22%. These rates rose considerably when patients were also prescribed benzodiazepines or were taking illegal drugs.

Risk factors for addiction to opioid medications

A number of research studies have looked at risk factors among chronic pain patients that make it more likely for them to be identified as engaged in addictive behaviors.

In the study cited above, Skurtveit, et al.,8 observed that new users of opioids as a group have a considerably smaller chance of becoming addicted than regular users as a group. Sullivan, et al.,10 found that having a history of substance dependence, high daily use of opioids, being young and having multiple pain complaints were risk factors. Hojsted, et al.,7 found that high daily use of opioids, use of benzodiazepine medications, use of alcohol, and anxiety and depression were risk factors for addiction. As indicated above, Morley, et al., found rates of misuse and abuse rose significantly amoung those who also take benzodiazepine medications (sedatives, which are also addictive) and/or illegal drugs.9

For more information

For cutting edge thougts on the distinction between physiological dependence to opioids and opioid addiction, please see our page, Should the Definition of Opioid Addiction Change?


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. The Clinical Journal of Pain, 13, 6-8.

2. Gatchel, R., J., & Okifuji, A. (2006). Evidence-based scientific data documenting the treatment and cost-effectiveness of comprehensive pain programs for chronic non-malignant pain. Journal of Pain, 7, 779-793.

3. Turk, D. C. (2002). Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain. The Clinical Journal of Pain, 18, 355-365.

4. Toblin, R. L., Mack, K. A., Perveen, G., & Paulozzi, L. J. (2011). A population-based survey of chronic pain and its treatment with prescription drugs. Pain, 152, 1249-1255.

5. Hojsted, J. & Sjogren, P. (2007). Addiction to opioids in chronic pain patients: A literature review. European Journal of Pain, 11, 490-518.

6. Martell, B. A., O’Connor, P. G., Kerns, R. D., Becker, W. C., Morales, K. H., Kosten, T. R., Fiellin, D. A. (2007). Systematic review: Opioid treatment for chronic back pain: Prevalence, efficacy, and association with addiction. Annals of Internal Medicine, 146, 116-127.

7. Hojsted, J., Nielsen, P. R., Guldstrand, S. K., Frich, L., & Sjogren, P. (2010). Classification and identification of opioid addiction in chronic pain patients. European Journal of Pain, 14, 1014-1020.

8. Skurtveit, S., Furu, K., Borchgrevink, P., Handal, M., & Fredheim, O. (2011). To what extent does a cohort of new users of weak opioid develop persistent or probable problematic opioid use? Pain, 152, 1555-1561.

9. Morley, K. I., Ferris, J. A., Winstock, A. R., & Lynskey, M. T. (2017). Polysubstance use and misuse or abuse of prescription opioid analgesics: A multi-level analysis of international data. Pain, 158, 1138-1144.

10. Sullivan, M. D., Edlund, M. J., Fan, M., DeVries, A., Braden, J. B., & Martin, B. C. (2010). Risks for possible and probable opioid misuse among recipients of chronic opioid therapy in commercial and Medicaid insurance plans: The TROUP Study. Pain, 150, 332-339.

Date of publication: March 25, 2013

Date of last modification: October 5, 2019

]]> (Murray J. McAllister, PsyD) Complications Fri, 27 Apr 2012 13:15:50 +0000