Opioid dependence and addiction during opioid treatment of chronic pain

Throughout the long history of opioid drug use by humans, it has been known that opioids are powerful analgesics, but they can cause addiction. It has also been observed, and is now substantiated by multiple reports and studies, that during opioid treatment of severe and short-term pain, addiction arises only rarely. However, when opioids are extended to patients with chronic pain, and therapeutic opioid use is not confined to patients with severe and short-lived pain, compulsive opioid seeking and addiction arising directly from opioid treatment of pain become more visible. Although the epidemiological evidence base currently available is rudimentary, it appears that problematic opioid use arises in some fraction of opioid-treated chronic pain patients, and that problematic behaviors and addiction are problems that need to be addressed. Since the potentially devastating effects of addiction can substantially offset the benefits of opioid pain relief, it seems timely to reexamine addiction mechanisms and their relevance to the practice of long-term opioid treatment for pain. This article reviews the neurobiological and genetic basis of addiction, its terminology and diagnosis, the evidence on addiction rates during opioid treatment of chronic pain and the implications of biological mechanisms in formulating rational opioid treatment regimes.     

Erratum to “Opioid dependence and addiction during opioid treatment of chronic pain” [Pain 129 (2007) 235–255]

Throughout the long history of opioid drug use by humans, it has been known that opioids are powerful analgesics, but they can cause addiction. It has also been observed, and is now substantiated by multiple reports and studies, that during opioid treatment of severe and short-term pain, addiction arises only rarely. However, when opioids are extended to patients with chronic pain, and therapeutic opioid use is not confined to patients with severe and short-lived pain, compulsive opioid seeking and addiction arising directly from opioid treatment of pain become more visible. Although the epidemiological evidence base currently available is rudimentary, it appears that problematic opioid use arises in some fraction of opioid-treated chronic pain patients, and that problematic behaviors and addiction are problems that need to be addressed. Since the potentially devastating effects of addiction can substantially offset the benefits of opioid pain relief, it seems timely to reexamine addiction mechanisms and their relevance to the practice of long-term opioid treatment for pain. This article reviews the neurobiological and genetic basis of addiction, its terminology and diagnosis, the evidence on addiction rates during opioid treatment of chronic pain and the implications of biological mechanisms in formulating rational opioid treatment regimes.     

Research Gaps on Use of Opioids for Chronic Noncancer Pain: Findings From a Review of the Evidence for an American Pain Society and American Academy of Pain Medicine Clinical Practice Guideline

Chronic noncancer pain is common and use of opioids is increasing. Previously published guidelines on use of opioids for chronic noncancer pain have been based primarily on expert consensus due to lack of strong evidence. We conducted searches on Ovid MEDLINE and the Cochrane databases through July 2008 to identify studies that addressed one or more of 37 Key Questions that a multidisciplinary expert panel identified as important to be answered to generate evidence-based recommendations on the use of opioids for chronic noncancer pain. A total of 14 systematic reviews, 38 randomized trials not included in a previously published systematic review, and 13 other studies met inclusion criteria. Almost all of the randomized trials of opioids for chronic noncancer pain were short-term efficacy studies. Critical research gaps on use of opioids for chronic noncancer pain include: lack of effectiveness studies on long-term benefits and harms of opioids (including drug abuse, addiction, and diversion); insufficient evidence to draw strong conclusions about optimal approaches to risk stratification, monitoring, or initiation and titration of opioid therapy; and lack of evidence on the utility of informed consent and opioid management plans, the utility of opioid rotation, the benefits and harms specific to methadone or higher doses of opioids, and treatment of patients with chronic noncancer pain at higher risk for drug abuse or misuse.PerspectiveCurrently, clinical decisions regarding the use of opioids for chronic noncancer pain need to be made based on weak evidence. Research funding priorities need to be set to address these critical research needs if the care of patients with chronic noncancer pain is to improve.     

Management of chronic noncancer pain in the primary care setting

While opioids are regarded as the mainstay of chronic pain management, their use is controversial in the minds of many primary care physicians due to clinical concerns about dependence, abuse, and addiction and medicolegal concerns regarding state and federal regulatory authorities. For patients with moderate to moderately severe pain, the treatment of choice is a long-acting opioid or opioid combination drug product to provide sustained analgesia along with improvements in sleep quality, compliance, and possibly quality of life. Careful screening of patients being considered for long-term opioid therapy with validated questionnaires can identify patients who may have difficulties in managing opioids. These patients should not be denied access to opioid therapy, but they do require focused monitoring and case management. Ongoing monitoring should focus on the 4 A's (ie, analgesia, activities of daily living, adverse effects, and aberrant drug-related behaviors), and all aspects of patient care must be thoroughly documented.     

Opioid tolerance and dependence — do they matter?

The use of opioids has long been accepted as the standard of care in patients with cancer and acute pain. Opioids can further be used effectively in specific subgroups of patients with chronic nonmalignant pain states. While the development of tolerance and physical dependence are known effects of opioids in cancer and noncancer pain populations, these patients can not be regarded as addicted. However, long-term therapy with short-acting opioids predisposes to tolerance and addiction. Recent research has confirmed the important role of psychopathologic and psychosocial conditions as predictors of failed opioid effectiveness in a significant number of noncancer pain subgroups. The clinical picture of failed therapy may be complicated by noncompliance, concealed consumption of psychotropic substances, and diversion of prescribed opioids for various purposes as, e.g., selling for profit, or sharing excess opioids with others. This article discusses the effects of opioid therapy, including tolerance, physical dependence, drug-aberrant behavior, drug history, psychopathology, and somatization.     

Problems and concerns of patients receiving chronic opioid therapy for chronic non-cancer pain

The value of chronic opioid therapy (COT) for chronic non-cancer pain (CNCP) patients is determined by a balance of poorly understood benefits and harms. Traditionally, this balance has been framed as the potential for improved pain control versus risks of iatrogenic addiction, drug diversion, and aberrant drug-related behaviors. These potential harms are typically defined from the providers’ perspective. This paper seeks to clarify difficulties with the long-term use of opioids for CNCP from the patients’ perspective. We used the Prescribed Opioids Difficulties Scale (PODS) to assess current problems and concerns attributed to opioid use by 1144 adults receiving COT. Subjects were grouped into low (56.9%), medium (25.6%) and high (17.5%) PODS scorers. Among patients with high PODS scores, 64% were clinically depressed and 78% experienced high levels of pain-related interference with activities, compared to 28% depressed and 60% with high interference with activities among those with low PODS scores. High levels of opioid-related problems and concerns were not explained by differences in pain intensity or persistence. Patients with medium to high PODS scores were often concerned about their ability to control their use of opioid medications, but prior substance abuse diagnoses and receiving excess days supply of opioids were much less common in these patients than depression and pain-related interference with activities. These results suggest two types of potential harm from COT attributed by CNCP patients to opioids: psychosocial problems that are distinct from poor pain control and opioid control concerns that are distinct from opioid misuse or addiction.     

Maladaptive Opioid Use Behaviors and Psychiatric Illness: What Should We Do with What We Know?

It is well established that opioids are broadly effective for chronic pain. Although there is some agreement that stable, moderate dosing is desirable; longer-term management of patients with chronic pain often confronts clinicians with difficult decisions regarding when to intensify opioid treatment and when to declare failure. Under these circumstances the concern for addiction arises with uncomfortable frequency in specialty settings. An emerging literature has defined a number of plausible markers of risk for aberrant opioid use behaviors in clinical chronic pain populations. Some of these risk factors involve the presence of comorbid psychiatric illnesses, which puts clinicians in the difficult position of deciding whether or not to limit treatment to patients who are more complex. The authors discuss the issues of bad behavioral outcomes in opioid therapy, the implications of this emerging literature for clinicians, and suggest broad areas in which researchers can improve the knowledge base with which clinicians operate.     

Chronic Pain: Reducing Costs Through Early Implementation of Adherence Testing and Recognition of Opioid Misuse

Abstract

Objective: To review the literature on costs associated with chronic pain therapy and to identify key contributing factors. Also, to assess the potential cost-saving benefits of monitoring pain treatment adherence using urine drug tests (UDTs), emphasizing their use in opioid therapy. Results: Reduced productivity, compensation costs, and treatment of comorbid conditions related to chronic pain contribute to the substantial financial burden of chronic pain management in the United States. The growing use of opioids for chronic pain increases the risk for drug nonadherence and associated drug abuse, potential addiction, and aberrant drug-related behaviors (ADRBs). Treatment of drug abuse increases health care costs; opioid abusers are 25 times more likely to require hospitalization than nonopioid abusers. Early detection of patient nonadherence using UDTs could significantly reduce costs of chronic pain therapy by allowing the physician to identify and treat patients' ADRBs related to controlled substances and drug addiction and abuse problems. Adherence in chronic pain may be determined by point-of-care (POC) tests, and more sensitive laboratory urine tests employing gas chromatography/mass spectrometry with high-performance liquid chromatography tests (LUTs). Cost-benefit studies suggest that the cost of LUTs to optimize adherence may reduce costs associated with nonadherence, such as inpatient clinical care and patient self-release. Current estimates indicate that appropriate use of LUTs could produce decreases up to 14.8-fold in the cost of chronic pain therapy. Conclusions: The cost benefits of UDTs can only be fully realized if physicians know how to define and detect various types of drug abuse, addiction, and diversion. Physicians should be educated on the proper implementation of POC tests and LUTs, and interpretation of adherence data. Early monitoring of drug adherence using POC tests and follow-up LUTs may provide substantial cost savings associated with health care issues incurred in nonadherent chronic pain patients, especially those taking opioid therapy.     

A pilot study into the problematic use of opioid analgesics in chronic non-cancer pain patients.

Controversy surrounds the use of strong opioid analgesic drugs for chronic non-cancer pain. Specialists have concluded that fears of problematic drug use are often unfounded. In contrast, others claim the existence of significant problems.'Problematic drug use' includes the following definitions; addiction, abuse, physiological dependence and tolerance.We present a case study and the results of a pilot, longitudinal, cohort study, via a pilot questionnaire, of 22 chronic pain clinic patients following a trial of opioid drugs.The results suggest that chronic non-cancer pain patients can be maintained on opioids with few problems, and likewise can withdraw with minimal adverse effects, other than a return of pain.     

Managing chronic nonmalignant pain: Overcoming obstacles to the use of opioids

Physicians involved in cancer pain management treat thousands of patients with opioids, whose effective analgesia improves overall functioning. Side effects generally are tolerable, and treatment can be maintained with stable doses for long periods. Problems with addiction are infrequent. Many physicians, however, assume that opioids should be used only for chronic malignant pain. Research and clinical experience have demonstrated that opioids can safely and effectively relieve most chronic moderate to severe nonmalignant pain. Fears of addiction, disciplinary action, and adverse effects result in ineffective pain management. With current information on the use of opioids in chronic nonmalignant pain, primary care physicians can overcome these obstacles. Guidelines must clearly define the role of the primary care physician in the proper management of pain and the integration of opioid therapy. Used appropriately, opioids may represent the only source of relief for many patients.     

What is the Case for Prescribing Long‐Acting Opioids Over Short‐Acting Opioids for Patients with Chronic Pain? A Critical Review

Introduction:   Effective pain management requires appropriate patient assessment, ongoing reassessment, and an understanding of the options available for the treatment of patients with chronic pain. Opioids have long been an important option in the management of moderate to severe chronic pain, but optimal use requires understanding the variety of choices currently available.
Methods:   Literature search was carried out using PubMed. Search terms included "steady state,""pharmacokinetics,""pharmacodynamics,""chronic non-cancer pain,""sustained release opioid," "extended release opioid," "controlled release opioid,""morphine,""oxymorphone,""hydromorphone,""oxycodone," and "fentanyl."
Results:   This search found 12 chronic pain studies that compared short- and long-acting opioids head-to-head. These were supplemented with representative studies from the chronic pain literature.
Discussion:   The objective of this article is to review clinical data for the use of long-acting and short-acting opioids in a variety of chronic noncancer pain conditions. Although some patients with chronic pain appear to prefer short-acting opioids, many patients receiving long-acting opioid formulations show improved treatment responses and better perception of quality of life. In addition, the sustained reductions in pain seen with long-acting opioid formulations may promote patients' focus on daily activities rather than on their pain, thereby improving therapy adherence and reducing pain-related anxieties.
Conclusion:   Long-term clinical trials of these formulations are needed to allow clinicians to make informed decisions about which patient groups might benefit most from these formulations.     

Opioid treatment of chronic pain in patients with addiction

Patients with a history of drug or alcohol addiction may present to physicians with pain complaints. The medical literature is weak on the treatment of pain with opioids in patients in recovery or active addiction. This is because inconsistent criteria were used to define addiction and the types of chronic pain. There are clear differences between physical dependence, tolerance, and addiction. Addiction is different from pseudoaddiction and must be determined by the patient's behavior after appropriate pain management. Long-acting opioids are often the medications of choice for moderate to severe pain control. Short-acting opioids can be used for breakthrough pain. There are many other medications that can enhance pain control as adjunctive analgesics. Drug-seeking behavior may be seen with either active addiction or pseudoaddiction, or as part of deviant behavior such as drug diversion. A way to distinguish between these conditions is by giving the patient appropriate pain medication and observing the pattern of behavior to determine which is causing the drug-seeking behavior. Safe prescribing of medications with abuse potential includes use of a medication agreement, setting goals with the patient, giving appropriate amounts of pain medication, monitoring with pill counts and drug screens, and careful documentation. Even patients with a history of addiction can benefit from opioid pain medications if monitored appropriately.