Topical review on the abuse and misuse potential of tramadol and tilidine in Germany.

BACKGROUND: Tramadol and tilidine (in combination with naloxone) are used as weak opioid analgesics in Germany. Tramadol is not scheduled in the German Narcotic Drugs Act. Tilidine is scheduled, whereas Tilidine in fixed combinations with naloxone is exempt from some of the provisions of the Narcotic Drugs Act. Recent reports on misuse of both substances led to an evaluation of their potential for misuse, abuse, and dependency by the expert advisory committee established by the German Federal Government, resident at the Federal Institute for Drugs and Medical Devices. METHODS: A subcommittee formulated key questions and identified available data sources for each of these questions. Additional information was solicited where necessary, including a survey among a panel of pharmacists, a survey in an addiction clinic, analysis of prescription patterns, and information from the boards of pharmacists of the federal states and the Federal Bureau of Criminal Investigation. RESULTS: Analgesic efficiency in the treatment of acute and chronic pain has been proven for both tramadol and tilidine/naloxone. For tramadol, high evidence has been confirmed in systematic reviews, and tramadol is listed in national and international guidelines on acute and chronic pain management. Animal and human studies found a low potential for misuse, abuse, and dependency for both substances. Information from 2 tramadol safety databases allowed calculation of the incidence of abuse or dependency as 0.21 and 0.12 cases per million defined daily dosages (DDDs), with lower incidences in recent years. For tilidine/naloxone, the incidence was calculated as 0.43 cases per million DDDs for oral solution and 0.18 for slow-release tablets. In an online survey among German pharmacies as well as in the reports from state pharmacy boards, fraud attempts were repeated more frequently with tilidine/naloxone than with tramadol in the last 2 years. The Federal Bureau of Criminal Investigations reported prescription fraud only with tilidine/naloxone and predominantly in the region of Berlin. Dependency on tramadol or tilidine/naloxone is reported only rarely from addiction counseling centers. One third of the patients surveyed in an addiction clinic reported experiences with tramadol or tilidine/naloxone, but mostly with duration of less than 4 weeks and with a medical prescription based on a reasonable indication. Also, occasional illegal use of opioid analgesics as a substitute of heroin was reported. An evaluation of pooled data from statutory health insurance companies found 2.5% of persons receiving at least 1 prescription of tramadol or the combination of tilidine and naloxone in 2009 (1.6% with tramadol and 1.0% with tilidine/naloxone). High usage with more than 180 DDDs per year was found in 8.6% of patients treated with tramadol and 17.2% of patients with tilidine/naloxone. CONCLUSIONS: In conclusion, the subcommittee of the expert advisory committee found a low potential for misuse, abuse, and dependency for tramadol, and a low prevalence in clinical practice. Considerable less information is available for the combination of tilidine and naloxone. However, the cumulation of evidence indicated a higher risk of misuse, abuse, and dependency for tilidine/naloxone solution, but not for slow-release tablets.

High use of tramadol in Germany: an analysis of statutory health insurance data.

PURPOSE: Tramadol is a weak opioid according to the World Health Organization pain ladder step II. It is one of the most prescribed analgesic substances in Germany, but tramadol and the step II opioids are very controversially discussed. We analysed patients with filled tramadol prescriptions with special emphasis on high use. METHODS: We used data from a German statutory health insurance for the year 2007. Patients older than 17 years with at least one tramadol prescription were analysed concerning demographic data, pain diagnoses, comorbidities, concomitant opioids, physician contacts and number of different prescribed substances. We fitted a logistic regression model to find relevant associations with high use (defined as >180 daily defined doses per year). RESULTS: From 22 ,946 insurants with filled tramadol prescriptions, 7.9% (n = 1812) are identified as high users; 90.9% of all tramadol patients and 93.1% of the high users have at least one pain diagnosis. The most frequent diagnoses are back pain (78.4% vs 77.1%) and arthritis pain (37.9% vs 41.8%). The results of the logistic regression model show associations between high use of tramadol and rising age, unspecific pain diagnoses, psychiatric co-morbidities, additional prescribed strong opioids and a high number of physician contacts. CONCLUSIONS: Despite some limitations, this study shows the prescriptions of tramadol in Germany in an authentic way. It seems that there are some 'challenging' patients that present a treatment dilemma for some prescribers. This might result in a high use of tramadol.