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Fatal unintentional intoxications with tramadol during 1995-2005
Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology. National Board of Forensic Medicine, Linköping, Sweden.
Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology. National Board of Forensic Medicine, Linköping, Sweden.
Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
National Board of Forensic Medicine, Linköping, Sweden.
2007 (English)In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 173, no 2-3, 107-111 p.Article in journal (Refereed) Published
Abstract [en]

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 μg/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 μg/g (range 1.1-12.0 μg/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. © 2007 Elsevier Ireland Ltd. All rights reserved.

Place, publisher, year, edition, pages
2007. Vol. 173, no 2-3, 107-111 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-40882DOI: 10.1016/j.forsciint.2007.02.007Local ID: 54460OAI: oai:DiVA.org:liu-40882DiVA: diva2:261731
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
In thesis
1. Psychoactive prescription drug use disorders, misuse and abuse: Pharmacoepidemiological aspects
Open this publication in new window or tab >>Psychoactive prescription drug use disorders, misuse and abuse: Pharmacoepidemiological aspects
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: There is a widespread and increasing use of psychoactive prescription drugs, such as opioid analgesics, anxiolytics, hypnotics and anti-epileptics, but their use is associated with a risk of drug use disorder, misuse and abuse. Today, these are globally recognized and emerging public health concerns.

Aim: The aim of this thesis is to estimate the prevalence of psychoactive prescription drug (PPD) use disorders, misuse and abuse, and to investigate the association with some potential risk factors.

Methods: A study using register data from forensic cause of death investigations investigated and described cases of fatal unintentional intoxication with tramadol (Study I). Based on register data on spontaneously reported adverse drug reactions (ADRs) reported cases of tramadol dependence were investigated and summarised (Study II). In a study in suspected drug-impaired drivers with a toxicology analysis confirming the intake of one out of five pre-specified PPDs, the prevalence of non-prescribed use was assessed and associated factors were investigated (Study III). From a cohort of patients initiating prescribed treatment with pregabalin, using data on prescription fills, a study investigated longitudinal utilisation patterns during five years with regards to use of the drug above the maximum approved daily dose (MAD), and factors associated with the utilisation patterns (Study IV).

Results: In the first study, 17 cases of unintentional intoxications were identified, of which more concerned men, the median age was 44 years and the majority used multiple psychoactive substances (alcohol, illicit drugs and prescription drugs). The second study identified 104 spontaneously reported cases of tramadol dependence, in which more concerned women, the median age was 45 years, and a third reported a history of substance abuse and 40% of past psychoactive medication use. In the third study, more than half of the individuals suspected of drug-impaired driving used the drug without a recent prescription. Non prescribed use was most frequent in users of benzodiazepines and tramadol, and was more likely in younger individuals and in multiple-substance users. In the last paper five longitudinal utilisation patterns were found in pregabalin users, with two patterns associated with a particularly high risk of doses above the maximum approved dosing recommendation. This pattern of use was associated with male sex, younger age, non-urban residency and a recent prescribed treatment with an antiepileptic or opioid analgesic drug.

Conclusions: This thesis shows that psychoactive prescription drug use disorders, misuse and abuse occur and may have serious and even fatal consequences. The prevalence varies between different drugs and populations. Abuse and misuse seem to be more common in young people. Fatal intoxications and misuse of prescribed drugs may be more common in men, while drug use disorders following prescribed treatment may be more common in women and non-prescribed use equally distributed between women and men. Individuals with a history of mental illness, substance use disorder or abuse, or of past use of psychoactive medications are likely important risk groups. In summary, the findings suggest a potential for improvements in the utilisation of psychoactive prescription drugs. The results may be useful in the planning of clinical and regulatory preventive interventions to promote the rational, individualised and safe use of such drugs.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 121 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1521
Keyword
Psychoactive prescription drugs, psychotropic drugs, prescription drug use disorders, prescription drug misuse, abuse, pharmacovigilance, drug utilization, pharmacoepidemiology
National Category
Substance Abuse Forensic Science Social and Clinical Pharmacy Pharmaceutical Sciences
Identifiers
urn:nbn:se:liu:diva-130768 (URN)10.3384/diss.diva-130768 (DOI)9789176857700 (ISBN)
Public defence
2016-09-09, Hasselquist-salen, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2016-08-23 Created: 2016-08-23 Last updated: 2017-12-12Bibliographically approved

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Tjäderborn, MicaelaJönsson, AnnaHägg, StaffanAhlner, Johan

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