Tramadol is an extensively used centrally acting analgesic and is considered a safe drug devoid of many serious adverse effects of traditional opioids. However, recently, toxicity and an abuse potential of tramadol have been reported. This study examined fatal unintentional tramadol intoxications among Swedish forensic autopsy cases between 1995 and 2005. All fatal intoxications were selected, in which toxic concentrations of tramadol (>1 microg/g femoral blood) had been detected, and where the forensic pathologist considered the intoxication unintentional and the fatal outcome at least partly explained by tramadol. Toxicology analyses, police reports, autopsy protocols and medical records were scrutinized. A total of 17 cases (eleven men and six women) of fatal unintentional tramadol intoxications were identified. For these cases the median age was 44 years (range 18-78 years) and the median tramadol concentration was 2.0 microg/g (range 1.1-12.0 microg/g). Other pharmaceutical substances, illicit drugs or ethanol were detected in addition to tramadol in all of these cases. In fact, intoxication with multiple drugs was considered the cause of death in 10 (59%) cases. However, in seven cases tramadol was the only substance present in toxic concentrations. A history of substance abuse was identified in 14 (82%) subjects and a present tramadol abuse in 8 (47%). These results suggest that fatal intoxications with tramadol may occur unintentionally and that subjects with a history of substance abuse may be at certain risk. Precaution is therefore warranted when prescribing tramadol in such patients.
BACKGROUND: Tramadol is a weak opioid analgesic, which is generally considered to be safe. However, conflicting data exist on the dependence potential of tramadol. OBJECTIVE: The aim of this study was to investigate occurrence of tramadol dependence and associated risk factors using spontaneously reported adverse drug reactions. METHODS: The Swedish database for spontaneously reported adverse drug reactions, Swedish Drug Information System (SweDIS), was searched for reports on tramadol dependence from 1 January 1995 until 31 December 2006. Selection was conducted based on the DSM-IV definition of dependence. Available information was scrutinised and registered and then presented descriptively. RESULTS: A total of 104 reports of tramadol dependence were identified, of which 60 (58%) concerned women. The median age (range) was 45 (15-84) years. Information on a history of substance abuse was present in 31 patients (30%) and 41 patients (39%) had a documented past or current use of a drug of abuse. Prescribed doses of tramadol ranged between 50-800 mg/day, and ingested doses between 50-4000 mg/day. Time of onset ranged from some weeks up to 4 years. In 72 (69%) cases the reaction was classified as serious, mainly due to hospitalisations for detoxification or discontinuation of tramadol. CONCLUSIONS: There is an occurrence of tramadol dependence in association with analgesic treatment within the recommended dose range. In susceptible patients a severe and serious dependence syndrome may develop. A history of abuse or use of a drug of abuse seems to be an important risk factor.