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Psychoactive prescription drug use disorders, misuse and abuse: Pharmacoepidemiological aspects
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
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.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1521
Keyword [en]
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
URN: urn:nbn:se:liu:diva-130768DOI: 10.3384/diss.diva-130768ISBN: 9789176857700 (Priint)OAI: diva2:954608
Public defence
2016-09-09, Hasselquist-salen, Campus US, Linköping, 09:00 (English)
Available from: 2016-08-23 Created: 2016-08-23 Last updated: 2016-08-23Bibliographically approved
List of papers
1. Fatal unintentional intoxications with tramadol during 1995-2005
Open this publication in new window or tab >>Fatal unintentional intoxications with tramadol during 1995-2005
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.

National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-40882 (URN)10.1016/j.forsciint.2007.02.007 (DOI)54460 (Local ID)54460 (Archive number)54460 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2016-08-23
2. Tramadol dependence: a survey of spontaneously reported cases in Sweden.
Open this publication in new window or tab >>Tramadol dependence: a survey of spontaneously reported cases in Sweden.
2009 (English)In: Pharmacoepidemiology and drug safety, ISSN 1099-1557Article in journal (Refereed) Published
Abstract [en]

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. Copyright (c) 2009 John Wiley & Sons, Ltd.

drug dependence; spontaneous reporting system; substance abuse; tramadol
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-51223 (URN)10.1002/pds.1838 (DOI)19827010 (PubMedID)
Available from: 2009-10-21 Created: 2009-10-21 Last updated: 2016-08-23
3. Non-prescribed use of psychoactive prescription drugs among drug-impaired drivers in Sweden
Open this publication in new window or tab >>Non-prescribed use of psychoactive prescription drugs among drug-impaired drivers in Sweden
Show others...
2016 (English)In: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 161, 77-85 p.Article in journal (Refereed) Published
Abstract [en]

Aims: To determine the prevalence of non-prescribed drug use among subjects suspected of drug impaired driving with a psychoactive prescription drug, and to identify associated factors. Methods: Subjects investigated for drug-impaired driving in Sweden during 2006-2009 with a confirmed intake of diazepam, flunitrazepam, tramadol, zolpidem or zopiclone were identified using the Swedish Forensic Toxicology Database. Information on dispensed prescription drugs was retrieved from the Swedish Prescribed Drug Register. Non-prescribed use was our outcome, defined as a psychoactive prescription drug intake confirmed by toxicological analysis in a subject by whom it was not dispensed in the 12 months preceding the sampling. Prevalence proportions were calculated for each drug and logistic regression was used to identify associated factors. Results: In total, 2225 subjects were included. The median age (range) was 34 (15-80) years and 1864 (83.8%) subjects were male. Non-prescribed use was found in 1513 subjects (58.7%); for flunitrazepam 103 (76.3%), diazepam 1098 (74.1%), tramadol 192 (40.3%), zopiclone 60 (29.7%), and zolpidem 60 (21.2%) subjects, respectively. Younger age and multiple-substance use were associated with non-prescribed use, whereas ongoing treatment with other psychoactive drugs was negatively associated with non prescribed use. Conclusions: Non-prescribed use of psychoactive prescription drugs was common in subjects suspected of drug-impaired driving and was more frequent for benzodiazepines and tramadol compared to zolpidem and zopiclone. The young and multi-substance users were more likely, whereas subjects with ongoing prescribed treatment with other psychoactive drugs were less likely, to use non-prescribed drugs.

Place, publisher, year, edition, pages
Prescription drug diversion; Non-prescribed use; Drug-impaired driving; Drug dispensing; Pharmacoepidemiology
National Category
Clinical Medicine
urn:nbn:se:liu:diva-127559 (URN)10.1016/j.drugalcdep.2016.01.031 (DOI)000373419100011 ()26875672 (PubMedID)

Funding Agencies|County Council of Ostergotland, Sweden [LIO-131751]; Forensic Science Centre, Sweden [CFV 121218]; Linkoping University, Sweden [LIU 2009-01356]

Available from: 2016-05-04 Created: 2016-05-03 Last updated: 2016-08-23

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