An easy-to-obtain drug As an unscheduled medication, tramadol can be obtained online, diverted from clinical settings, and purchased outside the United States. In both of the cases presented, the patients reported the ease with which they obtained and used very high doses of tramadol. These patients exhibited significant tolerance and were reportedly taking tramadol at three to five times the recommended maximum daily dose of 400 mg. The surreptitious acquisition and availability of tramadol for diversion has been documented in other cases.4,6 Some case reports have documented the financial problems that can result when dependent patients purchase tramadol over the Internet. Such monetary problems may be the first sign of drug dependence.4
Abuse or dependence The clinical signs and symptoms associated with abuse, dependence, and withdrawal associated with tramadol are very similar to those of opiates. While intoxication is accompanied by euphoria, sedation and/or excitation, nausea, and miosis, behavioral withdrawal symptoms are typically the opposite and are associated with depressed mood, craving, and drug-seeking. According to the American Psychiatric Association (APA), substance abuse exists when, over a 12-month period, recurrent use
• Results in inability to meet necessary obligations at work, school, or home
• Persists despite the potential for physical harm
• Causes legal problems
• Continues despite persistent or exacerbated social problems.13
Both of the patients presented here exhibited physical, psychological, and social consequences of use that meet the definition of substance abuse. However, one of the requirements of substance abuse is that patients not fulfill the criteria for dependence. In these cases, both patients exhibited signs of tramadol dependence. According to APA criteria, dependence requires three or more of the following during a 12-month period:
• Tolerance—a need for higher amounts of the substance to achieve the usual effect or a lesser effect from the amount customarily taken
• Withdrawal—evidenced by a typical withdrawal syndrome or the substitution of another substance to avoid withdrawal symptoms
• Greater substance use (in amount or duration) than intended
• Inability to control substance use
• Excessive amounts of time lost in obtaining the substance, using it, and recovering from its use
• Altered participation (ranging from a decrease to complete cessation) in social, work-related, or recreational activities
• Continued substance abuse despite awareness that the substance is causing persistent or exacerbated physical and psychological problems.13
Atypical withdrawal symptoms have also been reported from tramadol dependence, including confusion, delusions, paranoia, peripheral numbness, and hallucinations.11 These atypical symptoms were noted in the second patient presented. Clinicians who note signs of abuse, dependence, or withdrawal are urged to consult with an addictionist or pain management specialist.5 The treatment plan may then include drug detoxification, inpatient rehabilitation, outpatient care, and alternative forms of pain management.
A prudent approach Prior to prescribing any controlled substance, the prudent approach is to obtain a personal and family history profile regarding substance abuse or other compulsive behavioral disorders.13 Given the cases presented, this advice may also apply to prescribing tramadol. Furthermore, Case 2 reinforces the notion that physical or emotional abuse can prime the person for substance abuse at a later time. This patient had a previous history of substance abuse, emotional and physical abuse, and possible mental illness, all of which manifested in her chronic relapses. Primary care clinicians should be aware of the clinical differences between substance abuse, dependence, tolerance, and withdrawal (see Table 1) and should be comfortable in consulting with pain management and addiction specialists on the care of their patients. JAAPA
James D. Stoehr is a professor in the PA Program at Midwestern University, Glendale, Arizona. Alison Essary is an associate professor in the same program. Chrissi Ou is a fourth-year medical student at Arizona College of Osteopathic Medicine, Midwestern University. Rob Ashby specializes in addiction medicine and pain management in Scottsdale, Arizona. Michel Sucher is an addiction medicine specialist and president of Greenberg and Sucher, LLC, in Scottsdale. The authors have indicated no relationships to disclose relating to the content of this article.
DRUGS MENTIONED
Buprenorphine plus naloxone (Suboxone)
Hydrocodone
Meperidine (Demerol, generics)
Oxycodone (OxyContin, Oxydose)
Pentazocine (Talwin)
Sumatriptan (Imitrex, generics)
Tramadol (Ultram, Ryzolt, generics)
Tramadol/acetaminophen (Ultracet, generics)
Trazodone
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