What is the addiction risk associated with tramadol?

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Clinical Inquiries

What is the addiction risk associated with tramadol?

J Fam Pract. 2005 January;54(1):65-82

By

Todd McDiarmid, MD

Leslie Mackler, MSLS

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References

1. Brewer T, Colditz GA. Postmarketing surveillance and adverse drug reactions: current perspectives and future needs. JAMA 1999;281:824-829.

2. Brinker A, Bonnel RA, Beitz J. Abuse, dependence, or withdrawal associated with tramadol. Am J Psychiatry 2002;159:881-882.

3. Adverse Event Reporting System. Freedom of Information Report. Rockville, Md: Office of Drug Safety, Food and Drug Administration: search November 1997 to September 2004.

4. Drug Abuse Warning Network. Emergency Department Trends From DAWN: Final Estimates 1995 to 2002. Available at: dawninfo.samhsa.gov. Accessed on August 25, 2004.

5. 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.

6. Senay EC, Adams EH, Geller A, et al. Physical dependence on Ultram (tramadol hydrochloride): both opioid-like and atypical withdrawal symptoms occur. Drug Alcohol Depend 2003;69:233-241.

7. Knisely JS, Campbell ED, Dawson KS, Schnoll SH. Tramadol post-marketing surveillance in health care professionals. Drug Alcohol Depend 2002;68:15-22.

8. Liu ZM, Zhou WH, Lian Z, et al. Drug dependence and abuse potential of tramadol. Zhongguo Yao Li Xue Bao 1999;20:52-54.

9. FDA Drug Abuse Advisory Committee. The Scientific Evidence for Initiating a Scheduling Action for Ultrammadol hydrochloride). 1998. Available at: www.fda.gov.

10. Murray L, ed. Physicians’ Desk Reference. 58th ed. Montvale, NJ: Thomson PDR; 2004;2496.-

EVIDENCE-BASED ANSWER

Tramadol (Ultram, generic and with acetaminophen in Ultracet) carries a risk of substance abuse (strength of recommendation [SOR]: B, based on case report surveillance programs). While it appears that tramadol’s risk of substance abuse is low (SOR: B, based on case report surveillance programs), tramadol is associated with a withdrawal syndrome usually typical of opioid withdrawal (SOR: B, based on case report surveillance programs, and a prospective descriptive study).

Evidence summary

Tramadol is a novel, central-acting synthetic opioid with weak mu-opioid activity, and is approved for treatment of moderate to moderately severe pain in adults. Anecdotally, some clinicians have assumed this popular analgesic’s nonscheduled status under the Controlled Substance Act (CSA) means tramadol has no substance abuse potential. (The term “abuse” herein denotes substance abuse or dependence.)

Evidence of tramadol abuse in the US comes primarily from federally operated programs collecting adverse drug event (ADE) data. The MedWatch program of the Food and Drug Administration (FDA) provides a central depository for receiving and compiling postmarketing voluntary case reports. While passive reporting systems can significantly underestimate serious ADE numbers, these reports are often the first evidence of an ADE after a new drug’s release into the market.¹ MedWatch has received 766 case reports of abuse associated with tramadol, as well as 482 cases of withdrawal associated with tramadol from the drug’s initial US marketing in 1995 through September 2004.^2,3

The Drug Abuse Warning Network (DAWN) is a federally operated, national surveillance system that monitors trends in drug-related emergency department visits. Over the period from 1995 to 2002, DAWN reported drug-related emergency department visits mentioning tramadol in more than 12,000 cases. Tramadol case numbers significantly increased 165% during this time. For perspective, during the same period, DAWN found nalbuphine (Nubain, also not CSA scheduled) in 118 cases, propoxyphene drug combinations (CSA Class IV) in more than 45,000 cases, codeine drug combinations (CSA Classes III & V) in about 50,000 cases, and hydrocodone drug combinations (CSA Class III) in around 128,000 cases.⁴

Evidence-based answers from the Family Physicians Inquiries Network

What is the addiction risk associated with tramadol?

References

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