Potential for Abuse of Buprenorphine in Office-Based Treatment of Opioid Dependence
http://www.100md.com
《新英格兰医药杂志》
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.3,4,5 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 1 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,3,4,5 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.
Figure 1. Average Number of Cases of Abuse of Buprenorphine Products, Methadone, Tramadol, and Oxycodone per Drug-Abuse Expert.
The arrow indicates the launch date of buprenorphine for use in office-based treatment of opioid dependence. Q denotes quarter.
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.
References
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.
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.)
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.
Cicero TJ, Inciardi JA. Diversion and abuse of methadone prescribed for pain management. JAMA 2005;293:297-298.
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.
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.3,4,5 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 1 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,3,4,5 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.
Figure 1. Average Number of Cases of Abuse of Buprenorphine Products, Methadone, Tramadol, and Oxycodone per Drug-Abuse Expert.
The arrow indicates the launch date of buprenorphine for use in office-based treatment of opioid dependence. Q denotes quarter.
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.
References
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.
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.)
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.
Cicero TJ, Inciardi JA. Diversion and abuse of methadone prescribed for pain management. JAMA 2005;293:297-298.
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.