REVIEW
Issues in Long-term Opioid Therapy: Unmet Needs, Risks, and Solutions

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Both chronic pain and prescription opioid abuse are prevalent and exact a high toll on patients, physicians, and society. Health care professionals must balance aggressive treatment of chronic pain with the need to minimize the risks of opioid abuse, misuse, and diversion. A thorough, ongoing assessment can help fashion a multimodal therapeutic plan, stratify patients by risk, and identify those who may exhibit aberrant behaviors after receiving opioid therapy. Appropriate safeguards (eg, urine drug screens, pill counts) may be used when necessary. Because not all aberrant behaviors have the same origins or implications, physicians must consider a differential diagnosis and tailor therapy accordingly. Opioid formulations designed to deter and resist abuse are currently in late-stage clinical development and address some but not all aspects of inappropriate opioid use. By incorporating physical and pharmacological barriers to obtaining the euphoric effects of opioids, these novel formulations may minimize problematic opioid use. The formulations use a variety of strategies, for example, combining opioids with naltrexone or niacin or incorporating the opioid in a high-viscosity matrix designed to resist physical and chemical extraction. Nonopioid medications as well as cognitive, behavioral, and interventional techniques should be considered for all patients with chronic pain, particularly for those who are unable to safely take their opioids in a structured fashion. The aim of this article was to help physicians prescribe opioid medications safely and successfully to patients who need them. A PubMed literature search was conducted using the keywords risk management, assessment, aberrant behavior, addiction, prescription abuse, and abuse-deterrent.

Section snippets

THE ROLE OF OPIOIDS IN CHRONIC PAIN

Treatment options for chronic pain include nonpharmacological and pharmacological modalities. Choice of therapy should be guided by a comprehensive assessment, including history (eg, pain history, medical history, family history, psychosocial history, medications, past interventions), physical examination, and appropriate diagnostic studies. Underlying conditions, if present, such as a tumor or vertebral fracture causing spinal cord compression, should be treated as directly as possible while

RISK ASSESSMENT

If opioid therapy is considered for a patient, the risks of opioid abuse, misuse, and diversion should be carefully assessed. The object of risk assessment is to identify the likelihood that a patient will exhibit aberrant behaviors (eg, abuse, misuse, diversion, addiction; Table 223) once opioid therapy has been prescribed so that appropriate safeguards can be placed in his or her pain management plan.3, 24 Some patients are at greater risk for abuse, misuse, diversion, and addiction than

MONITORING

On the basis of risk assessment, patients can be stratified by their level of risk, and therapy can be structured appropriately to minimize risk and guide monitoring.6, 13 Patients at minimal risk can receive minimal structure, whereas those at greater risk can receive more structure, such as more frequent visits, fewer pills per prescription, specialist-level care (eg, an addiction specialist or psychotherapist), and UDTs. An opioid treatment agreement, discussed and signed by the patient

ABUSE-DETERRENT AND ABUSE-RESISTANT APPROACHES

Opioid formulations that incorporate barriers to common forms of manipulation are an emerging component of risk management. Novel subclasses of opioid formulations, incorporating pharmacological strategies and physical barriers, are designed to deter or resist misuse and abuse by making it difficult to obtain euphoric effects from opioid use. To obtain euphoric effects, most individuals who abuse opioids crush the tablets or capsules and snort or inject them, increasing opioid bioavailability.42

PHARMACOLOGICAL STRATEGIES

Pharmacological strategies have developed as either agonist-antagonist or agonist-additional active ingredient combinations. Agonist-antagonist formulations can be considered pharmacodynamic strategies because they act to reduce reward at the receptor level.43 An example of such a strategy is Embeda (King Pharmaceuticals, Bristol, TN), which combines morphine with an antagonist. If this formulation is ingested normally, the naltrexone remains latent; if it is crushed, the naltrexone is released

ABUSE-RESISTANT STRATEGIES

Abuse-resistant mechanisms use physical strategies that make extracting the active drug from its formulation more difficult. One such formulation is a controlled-release oxycodone, Remoxy (King Pharmaceuticals), formerly known as PTI-821, which sequesters oxycodone in a high-viscosity matrix. This investigational drug is intended to resist physical manipulation and chemical extraction used to alter drug delivery to unintended routes, such as injection, snorting, and other common methods of

CONCLUSION

Chronic pain and prescription opioid abuse are common and substantially affect patients, physicians, and society. Aggressive treatment of chronic pain must be balanced with the need to minimize the risks of opioid abuse, misuse, and diversion. Ongoing assessment can aid in developing a multimodal therapeutic plan, stratifying patients by risk, and identifying patients who may have aberrant behaviors after receiving opioid therapy. Not all aberrant behaviors have the same etiology, and thus

REFERENCES (51)

  • AG White et al.

    Direct costs of opioid abuse in an insured population in the United States

    J Manag Care Pharm

    (2005)
  • LJ Paulozzi et al.

    Increasing deaths from opioid analgesics in the United States

    Pharmacoepidemiol Drug Saf

    (2006)
  • HG Birnbaum et al.

    Estimated costs of prescription opioid analgesic abuse in the United States in 2001: a societal perspective

    Clin J Pain

    (2006)
  • DL Gourlay et al.

    Universal precautions in pain medicine: a rational approach to the treatment of chronic pain

    Pain Med

    (2005)
  • AM Trescot et al.

    Opioid guidelines in the management of chronic non-cancer pain

    Pain Physician

    (2006)
  • NP Katz et al.

    Foundations of opioid risk management

    Clin J Pain

    (2007)
  • National Pharmaceutical Council I et al.

    Scribd Web site. Pain: current understanding of assessment, management, and treatments. 2001

  • DB Carr et al.

    Evidence report on the treatment of pain in cancer patients

    J Natl Cancer Inst Monogr

    (2004)
  • KL Kirsh et al.

    The interface between pain and drug abuse the evolution of strategies to optimize pain management while minimizing drug abuse

    Exp Clin Psychopharmacol

    (2008)
  • CE Argoff

    Pharmacologic management of chronic pain

    J Am Osteopath Assoc

    (2002)
  • SD Passik et al.

    Opioid therapy in patients with a history of substance abuse

    CNS Drugs

    (2004)
  • CJ Woolf et al.

    Use and abuse of opioid analgesics: potential methods to prevent and deter non-medical consumption of prescription opioids

    Curr Opin Investig Drugs

    (2004)
  • LR Webster

    PTI-821: sustained-release oxycodone using gel-cap technology

    Expert Opin Investig Drugs

    (2007)
  • American Academy of Pain Medicine et al.

    The use of opioids for the treatment of chronic pain: a consensus statement from the American Academy of Pain

    Clin J Pain

    (1997)
  • PG Fine

    The evolving and important role of anesthesiology in palliative care

    Anesth Analg

    (2005)
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    Dr Passik is a consultant for and on the speakers bureau of Cephalon, King Pharmaceuticals, Wyeth, and PriCara, a division of Ortho-McNeil-Janssen Pharmaceuticals.

    This article is freely available on publication.

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