Correspondence

Potential for Abuse of Buprenorphine in Office-Based Treatment of Opioid Dependence

N Engl J Med 2005; 353:1863-1865October 27, 2005

Article

To the Editor:

Buprenorphine was approved by the Food and Drug Administration (FDA) in 2002 for the treatment of opioid addiction in certified physicians' offices. However, the FDA and the Drug Enforcement Administration (DEA) expressed concern that the use of buprenorphine in opioid-dependent populations would inevitably lead to its diversion and abuse.1,2 Thus, buprenorphine was moved from Schedule V of the Controlled Substances Act to Schedule III.1 In an effort to restrict the number of persons exposed to the drug, a limit was imposed of no more than 30 patients per qualifying certified physician.

We report on the abuse of buprenorphine products on the basis of data gathered through two well-established networks of several hundred geographically dispersed drug-abuse experts.3-5 When a suspected case was identified, the drug-abuse experts were asked to complete a structured questionnaire by means of a direct interview with each patient with suspected drug abuse. To place any abuse into perspective, we also assessed abuse of tramadol (an unscheduled drug); methadone (the standard pharmacologic treatment for opioid abuse; Schedule II); and oxycodone (a very widely abused Schedule II opioid analgesic4).

Figure 1Figure 1Average Number of Cases of Abuse of Buprenorphine Products, Methadone, Tramadol, and Oxycodone per Drug-Abuse Expert. shows the average number of case reports of abuse per drug-abuse expert for each calendar quarter of the study period for the drugs examined. Growing abuse of oxycodone was responsible by far for the greatest number, followed by methadone, tramadol, and buprenorphine. There were no statistically significant differences between tramadol abuse and buprenorphine abuse. As reported elsewhere,3-5 the majority of all prescription-drug abusers were young white men with extensive histories of substance abuse. More than one third of the buprenorphine abusers reported that they took the drug in an effort to self-medicate and ease heroin withdrawal.

These results indicate that there has been very little abuse of buprenorphine since its launch for the treatment of opioid addiction in the first quarter of 2003. The abuse found was no greater than that observed for the unscheduled drug tramadol and much less than that for the Schedule II drugs methadone and oxycodone. There are limitations to this preliminary study: none of our measures correct for the degree of exposure to the drugs in question, since data on exposure are not available. These data could show different rates (cases divided by exposure) from those reported here, but on the basis of the raw number of abuse cases, it would appear that the concern expressed by the FDA and DEA1,2 about a very large surge in abuse of buprenorphine resulting from its use in an opioid-dependent population may be unfounded, at least during the two years it has been available.

Theodore J. Cicero, Ph.D.
Washington University, St. Louis, MO 63110
cicerot@wustl.edu

James A. Inciardi, Ph.D.
University of Delaware, Coral Gables, FL 33134

Drs. Cicero and Inciardi report having received research grants and consulting fees from Purdue Pharma and Ortho-McNeil.

5 References

1. 1

   Drug Enforcement Administration (DEA), Department of Justice. Schedules of controlled substances: rescheduling of buprenorphine from Schedule V to Schedule III. Fed Regist 2002;67:62354-62370
   Medline

2. 2

   Center for Substance Abuse Treatment. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment improvement protocol (TIP) series 40. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2004. (DHHS publication no. (SMA) 04-3939.)
   

3. 3

   Cicero TJ, Adams EH, Geller A, et al. A postmarketing surveillance program to monitor Ultram (tramadol hydrochloride) abuse in the United States. Drug Alcohol Depend 1999;57:7-22
   CrossRef | Web of Science | Medline

4. 4

   Cicero TJ, Inciardi JA. Diversion and abuse of methadone prescribed for pain management. JAMA 2005;293:297-298
   CrossRef | Web of Science | Medline

5. 5

   Cicero TJ, Inciardi JA, Munoz A. Trends in abuse of OxyContin and other opioid analgesics in the United States: 2002-2004. J Pain 2005;6:662-672
   CrossRef | Web of Science | Medline

Citing Articles (11)

Citing Articles

1. 1

   Benjamin Doolittle, William Becker. (2011) A Case Series of Buprenorphine/Naloxone Treatment in a Primary Care Practice. Substance Abuse 32:4, 262-265
   CrossRef

2. 2

   Alexander R. Bazazi, Michael Yokell, Jeannia J. Fu, Josiah D. Rich, Nickolas D. Zaller. (2011) Illicit Use of Buprenorphine/Naloxone Among Injecting and Noninjecting Opioid Users. Journal of Addiction Medicine 5:3, 175-180
   CrossRef

3. 3

   Chris-Ellyn Johanson, Cynthia L. Arfken, Salvatore di Menza, Charles Roberts Schuster. (2011) Diversion and abuse of buprenorphine: Findings from national surveys of treatment patients and physicians. Drug and Alcohol Dependence
   CrossRef

4. 4

   Howard S. Smith. (2011) The Metabolism of Opioid Agents and the Clinical Impact of Their Active Metabolites. The Clinical Journal of Pain 27:9, 824-838
   CrossRef

5. 5

   Zev Schuman-Olivier, Mark Albanese, Sarah E. Nelson, Lolita Roland, Francyne Puopolo, Lauren Klinker, Howard J. Shaffer. (2010) Self-treatment: Illicit buprenorphine use by opioid-dependent treatment seekers. Journal of Substance Abuse Treatment 39:1, 41-50
   CrossRef

6. 6

   Enrico Moratti, Hamid Kashanpour, Tiziana Lombardelli, Maria Maisto. (2010) Intravenous Misuse of Buprenorphine. Clinical Drug Investigation 30, 3-11
   CrossRef

7. 7

   Louis Yi Ann Chai, C. B. Khare, Arlene Chua, Dale Andrew Fisher, Paul Ananth Tambyah. (2008) Buprenorphine Diversion: A Possible Reason for Increased Incidence of Infective Endocarditis among Injection Drug Users? The Singapore Experience. Clinical Infectious Diseases 46:6, 953-955
   CrossRef

8. 8

   Theodore J. Cicero, Hilary Surratt, James A. Inciardi, Alvaro Munoz. (2007) Relationship between therapeutic use and abuse of opioid analgesics in rural, suburban, and urban locations in the United States. Pharmacoepidemiology and Drug Safety 16:8, 827-840
   CrossRef

9. 9

   David A. Fiellin. (2007) The First Three Years of Buprenorphine in the United States: Experience to Date and Future Directions. Journal of Addiction Medicine 1:2, 62-67
   CrossRef

10. 10

    Gabriele Fischer, Beate Kayer. (2006) Substanzabhängigkeit vom Morphintyp – State-of-the-Art der Erhaltungstherapie mit synthetischen Opioiden. Psychiatrie und Psychotherapie 2:2, 39-54
    CrossRef

11. 11

    Bruno M??garbane, Raymond Hreiche, St??phane Pirnay, Nicolas Marie, Fr??d??ric J Baud. (2006) Does High-Dose Buprenorphine Cause Respiratory Depression?. Toxicological Reviews 25:2, 79-85
    CrossRef