David A. Fishbain, MD

The use of opioids for the treatment of chronic nonmalignant pain was mired in controversy for many years (Portenoy, 1996). It was once thought that long-term opioid use led to a downhill spiral associated with a loss of functional capacity and depressed mood (Ciccone et al., 2000). We now know that this is not the case. Other evidence also indicates that a subpopulation of patients with chronic pain can achieve sustained partial analgesia from opioid therapy without the occurrence of intolerable side effects (Savage, 1999). Impairment of daily activity, psychomotor speed, and sustained attention and mood have also been reported to improve with long-term opioid treatment for this population (Haythornthwaite et al., 1998). A meta-analysis of the opioid treatment literature has also indicated that, in general, patients with chronic pain will respond to long-term opioid therapy (Graven et al., 1999). Thus, at the present time, there is little controversy over whether opioids can be used for the treatment of pain when other options have been exhausted.

Although it appears that there has been a literature consensus reached on the need for chronic opioid treatment for patients with chronic pain if other treatments fail, there is a subpopulation within this group that is problematic. These are the patients who may demonstrate addiction to opioids.

In 2001, the American Academy of Pain Medicine, the American Pain Society and the American Society for Addiction Medicine approved the following definition for addiction (Savage et al., 2001):

Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. 

 criteria for drug dependence do not really address this concept of addiction. For example, of seven criteria (of which three are required to fulfill this diagnosis), one relates to tolerance and one relates to withdrawal. If patients with chronic pain are on significant opioids, they are invariably tolerant to opioids and manifest withdrawal when removed from them. Thus, these two criteria could lead to over-inclusiveness for this diagnosis. In addition, the criteria of "the substance is often taken in larger amounts  than intended" and "persistent desire  to cut down" can simply relate to the need to control pain. Thus, four out of seven criteria may lead to over-inclusiveness in the application of this diagnosis to the patient with chronic pain.

 criteria. Through a review process, my colleagues and I attempted to delineate what were the reported prevalence percentages for addiction in patients with chronic pain. We reported that different authors utilized different definitions and criteria (Fishbain et al., 1992). Overall, the prevalent percentages for drug abuse/dependence/addiction for patients with chronic pain was in the range of 3.2% to 18.9%. We cautioned that these results did not tap the concept of addiction and that the prevalence of addiction was likely at the lower end of this range.

There have been a significant number of other studies that have directly or indirectly explored this issue. Hoffmann et al. (1995) found an addiction rate of 23.4%, Chabal et al. (1997) found an addiction rate of 34% and Kouyanou et al. (1997) found a rate of 12%. There has also been one report relating to chronic pain populations at a U.S. Veterans' Affairs (VA) facility and a primary care setting. In this study, Reid et al. (2002) found that prescription opioid abusive behavior was recorded for 24% of the VA patients and 31% of the primary care patients. As "opioid abusive behavior" does not necessarily translate into addiction, one does not know how to interpret these results.

In addition, there have been two studies utilizing urine toxicologies for inpatients with chronic pain using illicit drugs. In the first study, Fishbain et al. (1999) reported that 8.4% of the patients had illicit drugs in their urine, while Rafii et al. (1990) reported a rate of 12.5%. Since illicit drug use has a high correlation with a predisposition to addiction in patients with chronic pain (Sees and Clark, 1993), these figures probably represent the lower end in the range for prevalence of addiction. Although the above studies attempted to develop prevalence percentages for substance use disorders, none of them utilized control groups. A study by Brown et al. (1996) compared rates for substance use among patients with chronic pain attending a family medicine clinic to patients attending for other reasons. There was no statistical difference in prevalence between the two groups. Thus, it is possible that the prevalence of drug addiction in patients with chronic pain is no greater than that in other patients. This statement is even more relevant if one understands that the aforementioned drug addiction data were reported from tertiary facilities where patients with chronic pain who have more significant problems are treated. While these data indicate that the prevalence of addiction may not be too much different from the general population, they are limited by the problems with the definition and the diagnosis of addiction.

What Are Aberrant Drug-Related Behaviors?

In 1994, Portenoy described a group of operational aberrant drug-related 

phenomenon that he felt characterized the definition of addiction as exemplified by its three aspects: 1) loss of control over drug use; 2) compulsive use; and 3) continued use despite harm. These behaviors are presented in 

 and can alert the physician to the possibility of addiction. Using a checklist for these behaviors, 388 patients with chronic pain maintained on opioids were monitored (Passik et al., 2002). The prevalence ranged from a high of 13.3% for unsanctioned dose escalation to a low of 1.1% for drug hoarding. It is interesting to note that the prevalence of behaviors that would clearly indicate addiction, such as injecting oral formulations and concurrent abuse of illicit drugs, was only at 1.5% and 1.9%, respectively. Passik et al. (2002) concluded that the incidence of aberrant drug-related behaviors was low. These behaviors do not necessarily represent addiction, but may be representative of other syndromes or diagnoses such as addiction, pseudo-addiction due to inadequate analgesia, other psychiatric diagnoses (encephalopathy, borderline personality disorder, depression, anxiety) (Portenoy, 1996). Because of this differential diagnosis, it is unknown which aberrant drug-related behaviors or what combination is predictive of true addiction.

Understanding the Concept of Pseudo-Addiction

The concept of pseudo-addiction can only be understood within the context of aberrant drug-related behavior. Pseudo-addiction is operationally defined as aberrant drug-related behaviors that make patients with chronic pain look like addicts. However, these behaviors stop if opioid doses are increased and pain improves (Weissman and Haddox, 1989). This indicates that the aberrant drug-related behaviors were actually a search for relief, i.e., pseudo-addiction. However, it is to be noted that there is little specific evidence for the concept of pseudo-addiction, which originated from one case report (Weissman and Haddox, 1989). Outside of one large-scale study reported as an abstract (McCarberg and Laskin, 2001), no studies on pseudo-addiction exist. In this study of 500,000 patients, 316 were identified as problem opioid patients. Most of these patients, however, appeared to be pseudo-addicts. There is also some collateral evidence for the pseudo-addiction concept. Arthritic rats appeared to self-administer opioids at rates required to control their pain, rather than for the rewarding effects of the drug (Colpaert et al., 2001). This indicates that the two behaviors may also be separated in humans.

It is almost impossible to differentiate a patient with chronic pain with addiction 

who escalates the dose of medication to obtain euphoria from a nonaddicted patient with under-treated pain, since both will exhibit aberrant drug-related behaviors (Weaver and Schnoll, 2002). The best approach for physicians is to provide more pain medication and to observe the patient for aberrant drug-related behaviors and some of the characteristics listed in 

Although the pseudo-addiction concept lacks significant scientific support, it has nevertheless become widely accepted within the pain-physician community. As such, this concept has now become a focus in some medicolegal cases (Fishbain, 2002). Thus, psychiatrists who do chronic opioid pain treatment, or who are planning to, should be aware of this concept and address it in their patient notes.

The central concept of this review is as follows: The pain literature has identified a possible clinical problem (pseudo-addiction) that can only be understood within the context of pain and aberrant drug-related behaviors. This concept awaits adequate scientific scrutiny, but appears to be clinically relevant.

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Articles

Although patients taking opioids for chronic pain may sometimes appear to display addictive behaviors, addiction may not be the case. How can you tell if addiction is the problem or if inadequate pain control is to blame?

David A. Fishbain, MD

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Chronic Opioid Treatment, Addiction and Pseudo-Addiction in Patients With Chronic Pain