Toxicological and pathological findings in a series of buprenorphine related deaths. Possible risk factors for fatal outcome

Seldén, Tor; Ahlner, Johan; Druid, Henrik; Kronstrand, Robert

doi:10.1016/j.forsciint.2012.03.016

Cited by 64 publications

(69 citation statements)

References 46 publications

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“…20 The second strand of research is looking at the negative consequences of illicit use, mainly in the form of methadone-and buprenorphine-related mortality among users not in treatment. 6,8,[26][27][28][29][30][31][32] The majority of such fatalities are caused by polyintoxication involving a broad array of different substances, often sedatives and alcohol. 6,29,31,32 Such deaths have made up a significant percentage of the opioid-related mortality in some countries, not least Sweden; since 2011 the combined number of methadone-and buprenorphine-related fatalities have exceeded heroin-related deaths.…”

Section: Introductionmentioning

confidence: 99%

Diversion of Methadone and Buprenorphine from Opioid Substitution Treatment: A Staff Perspective

Johnson

Richert

2014

Journal of Psychoactive Drugs

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BackgroundDiversion-patients who sell or share their medication-is a hotly debated but relatively unresearched phenomenon. We have investigated the prevalence of self-reported diversion of methadone and buprenorphine at OST programs in Sweden. We have also examined if demographic, treatment, and social factors can be associated with an increased risk of diversion. MethodsStructured interviews were conducted with 411 patients from eleven OST programs. A standardized questionnaire with 106 close-and five open-ended questions were used. 280 interviews were done on site, by the researchers, while 131 interviews were conducted by specially trained patients through privileged access interviewing. The data were analyzed through frequency-and averages-calculations, cross-tabulations, and logistic regression analysis. ResultsIn total, 24.1% (n=99) of the patients reported diversion in the past month. 67.6% (n=277) stated that they had diverted at some point. The peer interviews showed significantly higher levels of diversion (37.4% past month) compared with the researcher interviews (17.2%).Neither demographic factors, dosages, nor collection routines were associated with diversion.The likelihood of diversion was higher for patients on mono-buprenorphine (OR=5.64) and buprenorphine-naloxone (OR=2.10), than among methadone patients. Other factors which increased the likelihood of diversion were current illicit drug use (OR=5.60), having had 3 patients as a primary source of illicit methadone or buprenorphine prior to treatment (OR=3.39), and mainly socializing with active drug users (OR=2.12). ConclusionSelf-reported diversion was considerably higher than in previous studies. This is most likely due to the new methodological strategy we used, but may also partly be explained by low availability of OST in Sweden, leading to a high demand for the substances by heroin users outside treatment. Efforts to decrease diversion should primarily focus on psychosocial and lifestyle-changing interventions, and expanded access to treatment, rather than on control measures.

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Section: Introductionmentioning

confidence: 99%

Diversion of Methadone and Buprenorphine from Opioid Substitution Treatment: A Staff Perspective

Johnson

Richert

2014

Journal of Psychoactive Drugs

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“…Different intake modes may in turn be related to motives for use, such as the removal of withdrawal symptoms versus getting "high" (Daniulaityte et al, 2012;Harris et al, 2013;Ison et al, 2006;Otiashvili et al, 2010). Further, that a low frequency of buprenorphine use was associated with increased overdose risk could potentially be explained by low tolerance levels in those who use buprenorphine infrequently, as tolerance levels are considered an important mechanism in relation to drug overdoses (Darke et al, 1996;Seldén et al, 2012). Furthermore, previous literature has documented the risk of buprenorphine injecting in relation to non-lethal overdoses (Häkkinen et al, 2012;Nielsen et al, 2007), especially in high-doses and when combined with benzodiazepines and alcohol (Häkkinen et al, 2012;Lai et al, 2006;Schifano et al, 2005;Seldén et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Further, that a low frequency of buprenorphine use was associated with increased overdose risk could potentially be explained by low tolerance levels in those who use buprenorphine infrequently, as tolerance levels are considered an important mechanism in relation to drug overdoses (Darke et al, 1996;Seldén et al, 2012). Furthermore, previous literature has documented the risk of buprenorphine injecting in relation to non-lethal overdoses (Häkkinen et al, 2012;Nielsen et al, 2007), especially in high-doses and when combined with benzodiazepines and alcohol (Häkkinen et al, 2012;Lai et al, 2006;Schifano et al, 2005;Seldén et al, 2012). To discourage injecting some treatment programmes prefer to prescribe the combined buprenorphine-naltrexone formulation (Riksheim 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Even though buprenorphine is generally considered safer than methadone (Bernard et al, 2013;Ernst et al, 2002;Heinemann et al, 2000;Seymour et al, 2003;Vormfelde et al, 2001), there have been reported fatalities after buprenorphine snorting or injecting (Ferrant, 2011;Tracqui et al, 1998). Further, fatalities have also been reported after highdose buprenorphine consumption regardless of intake mode, especially when combined with benzodiazepines and alcohol (Häkkinen et al, 2012;Lai et al, 2006;Schifano et al, 2005;Seldén et al, 2012). However, the question remains as to whether illicit OSD use poses an independent risk for such adverse health outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Illicit use of opioid substitution drugs: Prevalence, user characteristics, and the association with non-fatal overdoses

Bretteville-Jensen¹,

Lillehagen²,

Gjersing³

et al. 2015

Drug and Alcohol Dependence

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Background and aims: Diversion of opioid substitution drugs (OSD) is of public concern. This study examined the prevalence, frequency, and predictors of illicit OSD use in a group of injecting drug users (IDUs) and assessed if such use was associated with non-fatal overdoses.Methods: Semi-annual cross-sectional interviews conducted in Oslo, Norway, (2006Norway, ( -2013, from 1,355 street-recruited IDUs. Hurdle, logistic, and multinomial regression models were employed.Results: Overall, 27% reported illicit OSD use in the past four weeks; 16.8% methadone, 12.5% buprenorphine, and 2.9% both drugs. Almost 1/10 reported at least one non-fatal overdose in the past four weeks, and roughly 1/3 reported such experience in the past year. Use of additional drugs tended to be equally, or more prevalent among illicit OSD users than other IDUs. In terms of illicit OSD use being a risk factor for non-lethal overdoses, our results showed significant associations only for infrequent buprenorphine use (using once or less than once per week). Other factors associated with non-fatal overdoses included age, education, homelessness, as well as the benzodiazepines, stimulants, and heroin use. Conclusions:Users of diverted OSD may represent a high-risk population, as they used more additional drugs and used them more frequently than other IDUs. However, illicit OSD use may be less harmful than previously assumed. After accounting for an extensive set of covariates, only infrequent illicit buprenorphine use, but not methadone use, was associated with non-fatal overdoses.

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“…These results are concerning as other studies have shown that frequent and heavy cocaine use inhibits the pharmacokinetics of buprenorphine, triggering opioid withdrawal symptoms possibly by P-gp induction (236). Further, there have been numerous reports of severe respiratory depression and death from concomitant use of buprenorphine with CNS depressants, particularly benzodiazepines (216,228,(237)(238)(239). However, the role of drug transporters in these dangerous DDIs has yet to be investigated.…”

Section: Buprenorphinementioning

confidence: 99%

Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions

et al. 2015

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Opioid-related deaths, abuse, and drug interactions are growing epidemic problems that have medical, social, and economic implications. Drug transporters play a major role in the disposition of many drugs, including opioids; hence they can modulate their pharmacokinetics, pharmacodynamics and their associated drug-drug interactions (DDIs). Our understanding of the interaction of transporters with many therapeutic agents is improving; however, investigating such interactions with opioids is progressing relatively slowly despite the alarming number of opioids-mediated DDIs that may be related to transporters. This review presents a comprehensive report of the current literature relating to opioids and their drug transporter interactions. Additionally, it highlights the emergence of transporters that are yet to be fully identified but may play prominent roles in the disposition of opioids, the growing interest in transporter genomics for opioids, and the potential implications of opioid-drug transporter interactions for cancer treatments. A better understanding of drug transporters interactions with opioids will provide greater insight into potential clinical DDIs and could help improve opioids safety and efficacy.

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Toxicological and pathological findings in a series of buprenorphine related deaths. Possible risk factors for fatal outcome

Cited by 64 publications

References 46 publications

Diversion of Methadone and Buprenorphine from Opioid Substitution Treatment: A Staff Perspective

Diversion of Methadone and Buprenorphine from Opioid Substitution Treatment: A Staff Perspective

Illicit use of opioid substitution drugs: Prevalence, user characteristics, and the association with non-fatal overdoses

Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions

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