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Systematic Review: Treatment Agreements and Urine Drug Testing to Reduce Opioid Misuse in Patients With Chronic Pain

Joanna L. Starrels, MD, MS; William C. Becker, MD; Daniel P. Alford, MD, MPH; Alok Kapoor, MD, MSc; Arthur Robinson Williams, MA; and Barbara J. Turner, MD, MSEd, Executive Deputy Editor
[+] Article and Author Information

From Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York; Yale University School of Medicine, New Haven, Connecticut; Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts; and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.


Preliminary results of this study were presented at the 32nd annual meeting of the Society of General Internal Medicine, Miami Beach, Florida, 1316 May 2009.

Grant Support: Through the Program of Research Integrating Substance Use Issues into Mainstream Health Care, funded by the Robert Wood Johnson Foundation, the National Institute on Drug Abuse, and the Substance Abuse and Mental Health Services Administration. Dr. Starrels was supported in part by the Robert Wood Johnson Foundation Clinical Scholars Program.

Acknowledgment: The authors thank Karen Lillie, Carlos Rodriguez, and Moonseong Heo for contributing to the literature search and the Montefiore Division of General Internal Medicine Substance Abuse Research Group.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-2037.

Requests for Single Reprints: Barbara J. Turner, MD, MSEd, Division of General Internal Medicine, University of Pennsylvania School of Medicine, 1123 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19134; e-mail, bturner@mail.med.upenn.edu.

Current Author Addresses: Dr. Starrels: Division of General Internal Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467.

Dr. Becker: Section of General Internal Medicine, Yale University School of Medicine, 367 Cedar Street, PO Box 208093, New Haven, CT 06520-8093.

Dr. Alford: Section of General Internal Medicine, Clinical Addiction, Research and Education Unit, Boston University School of Medicine and Boston Medical Center, 801 Massachusetts Avenue, 2nd Floor, Boston, MA 02118.

Dr. Kapoor: Section of General Internal Medicine, Boston University School of Medicine and Boston Medical Center, 801 Massachusetts Avenue, 2nd Floor, Boston, MA 02118.

Mr. Williams: 4229 Regent Square, Philadelphia, PA 19104.

Dr. Turner: Division of General Internal Medicine, University of Pennsylvania School of Medicine, 1123 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19134.

Author Contributions: Conception and design: J.L. Starrels, W.C. Becker, D.P. Alford, A. Kapoor.

Analysis and interpretation of the data: J.L. Starrels, W.C. Becker, D.P. Alford, A. Kapoor, A.R. Williams, B.J. Turner.

Drafting of the article: J.L. Starrels, D.P. Alford, A. Kapoor, A.R. Williams, B.J. Turner.

Critical revision of the article for important intellectual content: J.L. Starrels, W.C. Becker, D.P. Alford, A. Kapoor, B.J. Turner.

Final approval of the article: J.L. Starrels, W.C. Becker, D.P. Alford, A.R. Williams, B.J. Turner.

Statistical expertise: J.L. Starrels, W.C. Becker.

Obtaining of funding: B.J. Turner.

Administrative, technical, or logistic support: A.R. Williams, B.J. Turner.

Collection and assembly of data: J.L. Starrels, W.C. Becker, D.P. Alford, A.R. Williams, B.J. Turner.


Ann Intern Med. 2010;152(11):712-720. doi:10.7326/0003-4819-152-11-201006010-00004
Text Size: A A A

Background: Experts recommend opioid treatment agreements and urine drug testing to reduce opioid analgesia misuse, but evidence of their effectiveness has not been systematically reviewed.

Purpose: To synthesize studies of the association of treatment agreements and urine drug testing with opioid misuse outcomes in outpatients with chronic noncancer pain.

Data Sources: MEDLINE, PsycINFO, EMBASE, Cochrane Central Register of Controlled Clinical Trials (January 1966 to June 2009), reference lists, and expert contacts.

Study Selection: Original research addressing opioid medications, chronic pain, and treatment agreements or urine drug testing, with a sample size of 50 participants or more and published in English, Spanish, or French.

Data Extraction: Two investigators independently identified eligible studies, extracted data, and assessed study quality. The outcome of opioid misuse was defined as drug abuse, drug misuse, aberrant drug-related behavior, diversion, or addiction.

Data Synthesis: Of 102 eligible studies, 11 met inclusion criteria; 6 were in pain clinics and 5 were in primary care settings. Four primary care studies examined multicomponent strategies that included interdisciplinary support. All studies were observational and rated as poor to fair quality. In 4 studies with comparison groups, opioid misuse was modestly reduced (7% to 23%) after treatment agreements with or without urine drug testing. In the other 7 studies, the proportion of patients with opioid misuse after treatment agreements, urine drug testing, or both varied widely (3% to 43%).

Limitations: Diversity of interventions and opioid misuse measures precluded meta-analysis. Most studies evaluated combinations of interventions.

Conclusion: Relatively weak evidence supports the effectiveness of opioid treatment agreements and urine drug testing in reducing opioid misuse by patients with chronic pain. Further research on effective ways to monitor and reduce opioid misuse is needed, especially in primary care settings.

Primary Funding Source: Substance Abuse and Mental Health Services Administration, National Institute on Drug Abuse, and Robert Wood Johnson Foundation.

Figures

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Figure.
Study flow diagram.

*Seven studies evaluated management strategies incorporating both treatment agreements and urine drug testing.

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Yes, but urine drug testing is still an invaluable resource for primary care
Posted on June 10, 2010
Gary M. Reisfield
University of Florida College of Medicine Department of Psychiatry, Division of Addiction Medicine
Conflict of Interest: None Declared

TO THE EDITOR:

We commend Starrels and colleagues for their excellent systematic review and wholeheartedly agree that more rigorous studies are needed to determine the roles of treatment agreements and urine drug testing (UDT) in the reduction of prescription opioid misuse. The authors might have emphasized, however, that in addition to the reduction of opioid misuse, for which they found weak supportive evidence, UDT plays an invaluable role in the detection of (a) abuse of and addiction to prescribed opioids; (b) abuse of and addiction to illicit drugs and non-prescribed controlled substances, and (c) diversion of prescribed opioids. The abuse of prescription opioids in the United States has reached epidemic proportions. Heit and Gourlay, in their accompanying editorial, point out that, in recent years, the number of new nonmedical users of prescription opioids has equaled or exceeded the number of new users of marijuana (1). Left unstated were the provenance of the opioids and the consequences of their use. As prescriptions for opioid analgesics have increased dramatically in recent years, there have been parallel increases in ER mentions, hospitalizations, and deaths related to these medications. In fact, rates of poisoning mortality involving opioid analgesics have been exponentially higher than those involving heroin and cocaine (2). And it should be sobering to all clinicians that most of the opioids destined for nonmedical use in the United States originate from valid physician prescriptions (3). Reducing prescription opioid misuse remains a vexing problem and is dependent on multiple patient, physician, and system factors. However, data supporting the utility of UDT in the detection of opioid-related problems is unequivocal as illustrated, for example, by the seminal study by Katz and colleagues (4), demonstrating that UDT is perhaps the single most important surveillance technique for detecting illicit drug use in chronic opioid analgesic therapy.

Our concern is that the Starrels and colleagues paper, in highlighting the dearth of quality evidence supporting the role of UDT in reducing opioid misuse â"“ while devoting a single sentence its role in detecting opioid and other substance use disorders â"“ will provide yet another pretext for the vast majority of primary care physicians who prescribe opioid analgesics but never drug test (5), to continue to never drug test, thereby wasting valuable opportunities to identify and address drug-related problems before they end in tragedy.

References

1. Heit HA, Gourlay DL. Tackling the difficult problem of prescription opioid misuse. Ann Intern Med. 2010;152:747-748.

2. Paulozzi LJ, Yongli X. Recent changes in drug poisoning mortality in the United States by urban-rural status and by drug type. Pharmacoepidemiology and Drug Safety. 2008;17:997-1005.

3. Substance Abuse and Mental Health Services Administration. (2008). Results from the 2007 National Survey on Drug Use and Health: National Findings (Office of Applied Studies, NSDUH Series H-34, DHHS Publication No. SMA 08-4343). Rockville, MD.

4. Katz NP, Sherbourne S, Beach M, Rose RJ, Vielguth J, Bradley J, et al. Behavioral monitoring and urine toxicology testing in patients receiving long-term opioid therapy. Anesth Analg. 2003;97;1097-1102.

5. Bhamb B, Brown D, Hariharan J, Anderson J, Balousek S, Fleming MF. Survey of select practice behaviors by primary care physicians on the use of opioids for chronic pain. Curr Med Res Opin. 2006;22:1859-1865.

Gary M. Reisfield, M.D.

Noni A. Graham, M.P.H.

Mark S. Gold, M.D.

Division of Addiction Medicine Department of Psychiatry University of Florida College College of Medicine

Conflict of Interest:

None declared

In Response to Dr. Reisfield
Posted on August 4, 2010
Joanna L. Starrels
Albert Einstein College of Medicine and Montefiore Medical Center
Conflict of Interest: None Declared

We agree with Dr. Reisfield that urine drug testing (UDT) is a valuable tool for monitoring patients who are prescribed long-term opioid medications for chronic pain, but our endorsement of its use in primary care is tempered by its limitations. UDT can detect use of illicit or non- prescribed drugs that is not disclosed by patients, which is essential to managing the risks associated with prescribed opioids. When ordered and interpreted correctly, UDT can also detect non-use of prescribed opioids. However, while UDT detects these two types of aberrant behavior (i.e., inappropriate use or non-use of controlled substances), current evidence does not support the claim that UDT can go further, to detect the clinical diagnoses of opioid use disorders (i.e., abuse and dependence) or the crime of diversion (i.e., selling or giving away). Indeed, the Katz article referenced by Dr. Reisfield only found that UDT is effective in detecting "behaviors suggestive of inappropriate medication use" (1). To detect the more serious outcomes of abuse, dependence, or diversion, serial UDT results over time need to be interpreted along with data from other sources, including patient interviews, physical examination, pill counts, and monitoring of patient behaviors such as requests for early refills.

While we highlight gaps in the scientific literature about UDT, we agree that the public health threat posed by opioid misuse is significant and UDT may be useful for detecting proximal outcomes (inappropriate drug use or non-use). However, a study of 80 primary care physicians by Dr. Reisfield and colleagues reported that even those who performed UDT demonstrated poor knowledge of how to interpret the results (2). Accurate interpretation of UDT results requires an understanding of the type of assay ordered, major and minor opioid metabolic pathways, expected drug detection times, and potential causes of false positives and negatives. Misinterpretation of these results can harm the physician-patient alliance or patient well-being. For example, we are aware of physicians who inappropriately discontinued synthetic opioids (e.g., fentanyl) because they thought an immunoassay-based UDT that was negative for natural opiates (i.e., morphine, codeine) signified evidence of diversion. We recommend that physicians become better educated about the use and limitations of UDT (3), and consult their lab toxicologist with questions about which test to order and how to interpret abnormal results. We also encourage researchers to continue to investigate best practices regarding UDT and other risk management strategies for patients prescribed long-term opioids.

Joanna L. Starrels, MD, MS Albert Einstein College of Medicine and Montefiore Medical Center Bronx, NY

Daniel P. Alford, MD, MPH Boston University School of Medicine and Boston Medical Center Boston, MA

Barbara J. Turner, MD, MSEd University of Pennsylvania School of Medicine Philadelphia, PA

References

1. Katz NP, Sherburne S, Beach M, et al. Behavioral monitoring and urine toxicology testing in patients receiving long-term opioid therapy. Anesthesia & Analgesia. 2003;97(4):1097-102.

2. Reisfield GM, Webb FJ, Bertholf RL, Sloan PA, Wilson GR. Family physicians' proficiency in urine drug test interpretation. Journal of Opioid Management. 2007;3(6).

3. Heit HA, Gourlay DL. Urine drug testing in pain medicine. Journal of Pain & Symptom Management. 2004;27(3):260-7.

Conflict of Interest:

None declared

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