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).
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