Addictive medication in relation to drug treatment and overdose death

Abstract

Background The involvement of the addictive medications, benzodiazepines (BZDs) and prescription opioids, including opioid maintenance treatment (OMT) medications, have increasingly contributed to the high overdose death rates in Denmark and Norway during the past decades. Investigating prescription patterns and patient behavior in relation to drug treatment and overdose deaths is important to increase our knowledge on how these addictive medications are used, misused, and how they may contribute to overdose deaths. Study aims The overall aim of the thesis was to acquire new knowledge of the involvement of addictive medications in the treatment of populations with drug use disorders (DUDs) and also in overdose deaths to improve treatment approaches and reduce detrimental outcomes in a vulnerable group of individuals. More specifically the aim was to investigate prescription patterns and use of addictive medication in relation to drug treatment and overdose deaths among populations in Denmark and Norway. Furthermore, to compare overdose cases with and without detection of legally prescribed addictive medications and investigate factors associated with having detection of non-prescribed addictive medication. Materials and methods This thesis was based on three different cohorts/samples from two countries: A Danish nationwide cohort including individuals admitted for treatment for DUDs in 2000-2010 (n=33,203); a Norwegian sample including overdose deaths in the capital city, Oslo, in 2006-2008 (n=167), and; a Danish sample including overdose deaths in Copenhagen, Aarhus, and Odense Municipality in 2008-2011 (n=130). The cohorts/samples were linked with data from population registries, local based registries, and journal reviews by using a unique identification number assigned to all Danish and Norwegian citizens. Results Overall, in the period after entering treatment and in the period prior to overdose death, addictive medication was often prescribed to individuals with DUD. In both periods, inappropriate prescription patterns were identified. During the first year after admission to DUD treatment, about one-quarter of the individuals (26.2%) were prescribed BZDs. Of these, about one-third (35.5%) were prescribed BZDs at dose levels that might indicate inappropriate use, and about one-third (34.6%) were prescribed more than one type of BZDs. Particularly individuals with opioid use (43.2%) were commonly prescribed BZDs. Admitting to treatment for a DUD did not increase the specialized psychiatric treatment coverage of this patient group, disregarding use of prescribed BZDs. Among overdose deaths in Denmark and Norway, the prescribed doses of the addictive medications among the deceased were in general higher than recommended. Further, the control/monitoring measures were insufficient and allowing use of multiple prescribing physicians (Norway), low levels of supervised intake of OMT medication (Denmark), and use of multiple prescribed addictive medications (Denmark). We investigated the deceased with detection of prescribed vs. non-prescribed addictive medication. In the Norwegian sample, we found that a lower proportion of the deceased (with detection of the target medications) had been prescribed BZDs (28.1%), strong analgesics (33.3%), or BZDs plus strong analgesics (50.0%) four weeks prior to death. However, in Denmark the majority of deceased with methadone-related overdose deaths (63.1%) were prescribed methadone as part of OMT at the time of death. In the Norwegian sample, detection of non-prescribed BZDs and/or strong analgesics was associated with younger age (a-OR=4.9; 95% CI, 1.4-18.0) and to have a permanent place of residence outside Oslo (a- OR=2.9; 1.1-8.1). In the Danish sample, detection of non-prescribed methadone was associated with younger age of 30 years or below (a-OR=9.5; 1.8-50.5), concomitant detection of 6-MAM/heroin (a-OR=3.1; 1.2-7.8), and non-prescribe