Bup Feeds

Buprenorphine Response as a Function of Neurogenetic Polymorphic Antecedents: Can Dopamine Genes Affect Clinical Outcomes in Reward Deficiency Syndrome (RDS)?

Buprenorphine Research (PubMed) - Wed, 02/11/2015 - 8:00am
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Buprenorphine Response as a Function of Neurogenetic Polymorphic Antecedents: Can Dopamine Genes Affect Clinical Outcomes in Reward Deficiency Syndrome (RDS)?

J Addict Res Ther. 2014;5

Authors: Blum K, Oscar-Berman M, Jacobs W, McLaughlin T, Gold MS

Abstract
There is a plethora of research indicating the successful treatment of opioid dependence with either buprenorphine alone or in combination with naloxone (Suboxone®). However, we encourage caution in long-term maintenance with these drugs, albeit, lack of any other FDA approved opioid maintenance compound to date. Our concern has been supported by severe withdrawal (even with tapering of the dosage of for example Suboxone® which is 40 times more potent than morphine) from low dose of buprenorphine (alone or with naloxone). In addition our findings of a long-term flat affect in chronic Suboxone® patients amongst other unwanted side effects including diversion and suicide attempts provides impetus to reconsider long-term utilization. However, it seems prudent to embrace genetic testing to reveal reward circuitry gene polymorphisms especially those related to dopaminergic pathways as well as opioid receptor(s) as a way of improving treatment outcomes. Understanding the interaction of reward circuitry involvement in buprenorphine effects and respective genotypes provide a novel framework to augment a patient's clinical experience and benefits during opioid replacement therapy.

PMID: 25664200 [PubMed - as supplied by publisher]

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Determination of Buprenorphine, Norbuprenorphine and Naloxone in Fingernail Clippings and Urine of Patients Under Opioid Substitution Therapy.

Buprenorphine Research (PubMed) - Wed, 02/11/2015 - 8:00am
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Determination of Buprenorphine, Norbuprenorphine and Naloxone in Fingernail Clippings and Urine of Patients Under Opioid Substitution Therapy.

J Anal Toxicol. 2015 Feb 7;

Authors: Tzatzarakis MN, Vakonaki E, Kovatsi L, Belivanis S, Mantsi M, Alegakis A, Liesivuori J, Tsatsakis AM

Abstract
The aim of this study was to develop and validate a method for the determination of buprenorphine (BUP), norbuprenorphine (NBUP) and naloxone (NAL) in fingernails and urine samples collected from former heroin users under suboxone substitution therapy. The analytes were extracted by solid-liquid or solid-phase extraction and were analyzed by liquid chromatography-mass spectrometry. The validation of the analytical methods developed included linearity, recovery, accuracy, precision, ion suppression, sensitivity of interfaces and limits of determination and quantification. The validated methods were applied to samples from 46 individuals. The majority of the urine samples were positive for all analytes (93.5% for BUP, 95.7% for NBUP and 84.8% for NAL). In nails, a higher detection rate was observed for NBUP and BUP (89.1%), compared with NAL (10.9%). The median values of the NBUP/BUP and the NAL/BUP ratio were 2.5 and 0.3 in urine and 0.8 and 0.3 in nails, respectively. A statistically significant correlation was found between the BUP, NBUP and total BUP (BUP and NBUP) concentrations in urine and those in nails. A weak correlation was observed between the daily dose (mg/day) and total BUP (P = 0.069), or NBUP (P = 0.072) concentrations in urine. In contrast, a strong correlation was found between the total amount of BUP administered during the last 12 months and total BUP (P = 0.038), or NBUP (P = 0.023) concentrations in urine. Moreover urine BUP, NBUP and total BUP concentrations correlated significantly. Our study demonstrated successfully the application of the developed method for the determination of the three analytes in urine and nails.

PMID: 25663675 [PubMed - as supplied by publisher]

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Sources of prescription opioids among diagnosed opioid abusers.

Buprenorphine Research (PubMed) - Wed, 02/11/2015 - 8:00am
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Sources of prescription opioids among diagnosed opioid abusers.

Curr Med Res Opin. 2015 Feb 7;:1-19

Authors: Shei A, Rice JB, Kirson NY, Bodnar K, Birnbaum HG, Holly P, Ben-Joseph R

Abstract
Abstract Objective: Diversion and abuse of prescription opioids are important public health concerns in the U.S. This study examined possible sources of prescription opioids among patients diagnosed with opioid abuse. Methods: Commercially-insured patients aged 12-64 diagnosed with opioid abuse/dependence ("abuse") were identified in OptumHealth Reporting and Insights medical and pharmacy claims data, 2006-2012, and required to have continuous eligibility over an 18-month study period surrounding the first abuse diagnosis. We examined whether abusers had access to prescription opioids through their own prescriptions and/or to diverted prescription opioids through family members' prescriptions obtained prior to the abuser's first abuse diagnosis. For comparison, we examined access to prescription opioids of a reference population of non-abusers. Sensitivity analyses focused on patients initially diagnosed with opioid dependence and, separately, abusers not previously treated with buprenorphine. Results: Of the 9,291 abusers meeting the selection criteria, 79.9% had an opioid prescription prior to their first abuse diagnosis. 20.1% of abusers did not have an opioid prescription prior to their first abuse diagnosis, of which approximately half (50.8%) had a family member who had an opioid prescription prior to the abuser's first abuse diagnosis (compared to 42.2% of non-abusers). Similar results were found among patients initially diagnosed with opioid dependence and among abusers not previously treated with buprenorphine. Limitations: The study relied on the accuracy of claims data to identify abusers, but opioid abuse is often undiagnosed. In addition, only prescription claims that were reimbursed by a health plan were included in the analysis. Conclusions: While most abusers had access to prescription opioids through their own prescriptions, many abusers without their own opioid prescriptions had access to prescription opioids through family members and may have obtained prescription opioids that way. Given the study design and data source, this is likely a conservative estimate of prescription opioid diversion.

PMID: 25661018 [PubMed - as supplied by publisher]

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Morphine and buprenorphine do not alter leukocyte cytokine production capacity, early apoptosis, or neutrophil phagocytic function in healthy dogs.

Buprenorphine Research (PubMed) - Wed, 02/11/2015 - 8:00am
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Morphine and buprenorphine do not alter leukocyte cytokine production capacity, early apoptosis, or neutrophil phagocytic function in healthy dogs.

Res Vet Sci. 2015 Jan 21;

Authors: Monibi FA, Dodam JR, Axiak-Bechtel SM, Amorim J, Zhang Y, Tsuruta K, Mann FA, DeClue AE

Abstract
Opioids have immunomodulatory properties in many species, but there is little information pertaining to these properties in dogs. Our objective was to compare the in vivo effects of morphine, buprenorphine, and control solution on innate immune system function and apoptosis in healthy dogs. Six adult dogs received a 24-hour infusion of morphine, buprenorphine, or control solution (saline) in a randomized, controlled, crossover block design. Leukocyte apoptosis, phagocytosis, and oxidative burst were evaluated using flow cytometry. Lipopolysaccharide, lipoteichoic acid, and peptidoglycan-stimulated leukocyte production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 were determined using canine specific multiplex assays. No significant treatment effects were detected among groups. These data suggest that healthy dogs could be less sensitive to the immunomodulatory effects of acute opioid administration compared with other species. Larger investigations in healthy and immunologically challenged dogs are recommended prior to application of these results in clinical patients.

PMID: 25660046 [PubMed - as supplied by publisher]

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Adolescents at Risk: Pain Pills to Heroin: Part II.

Buprenorphine Research (PubMed) - Fri, 02/06/2015 - 7:30am

Adolescents at Risk: Pain Pills to Heroin: Part II.

J Psychosoc Nurs Ment Health Serv. 2015 Feb 1;53(2):27-30

Authors: Fogger S, McGuinness TM

Abstract
Casually exposing adolescents to prescription opioid agents may escalate to daily use. A trend exists for adolescents using prescription opioid agents to substitute heroin because it is significantly cheaper than pills (approximately half of the cost) and is often more readily available. Additionally, it is more potent than most prescription opioid agents and carries increased risks of overdose and death. Although treatment for substance use disorders has traditionally centered on total abstinence, opioid replacement therapy (ORT) is an option that saves lives and prevents overdose deaths. In the United States, ORT is based on two medicines: methadone and buprenorphine. These drugs can be substituted for other opiate agents and have much lower overdose risks. Nursing implications and web-based resources for teaching are presented. [Journal of Psychosocial Nursing and Mental Health Services, 53(2), 27-30.].

PMID: 25654572 [PubMed - as supplied by publisher]

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Analysis of barriers to adoption of buprenorphine maintenance therapy by family physicians.

Buprenorphine Research (PubMed) - Thu, 02/05/2015 - 8:00am
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Analysis of barriers to adoption of buprenorphine maintenance therapy by family physicians.

Rural Remote Health. 2015 Jan-Mar;15(1):3019

Authors: DeFlavio JR, Rolin SA, Nordstrom BR, Kazal Jr LA

Abstract
INTRODUCTION: Opioid abuse has reached epidemic levels. Evidence-based treatments such as buprenorphine maintenance therapy (BMT) remain underutilized. Offering BMT in primary care settings has the potential to reduce overall costs of care, decrease medical morbidity associated with opioid dependence, and improve treatment outcomes. However, access to BMT, especially in rural areas, remains limited. This article will present a review of barriers to adoption of BMT among family physicians in a primarily rural area in the USA.
METHODS: An anonymous<b> </b>survey of family physicians practicing in Vermont or New Hampshire, two largely rural states, was conducted. The survey included both quantitative and qualitative questions, focused on BMT adoption and physician opinions of opioids. Specific factors assessed included physician factors, physicians' understanding of patient factors, and logistical issues.
RESULTS: One-hundred and eight family physicians completed the survey. Approximately 10% were buprenorphine prescribers. More than 80% of family physicians felt they regularly saw patients addicted to opiates. The majority (70%) felt that they, as family physicians, bore responsibility for treating opiate addiction. Potential logistical barriers to buprenorphine adoption included inadequately trained staff (88%), insufficient time (80%), inadequate office space (49%), and cumbersome regulations (37%). Common themes addressed in open-ended questions included lack of knowledge, time, or interest; mistrust of people with addiction or buprenorphine; and difficult patient population.
CONCLUSIONS: This study aims to quantify perceived barriers to treatment and provide insight expanding the community of family physicians offering BMT. The results suggest family physicians are excellent candidates to provide BMT, as most report regularly seeing opioid-addicted patients and believe that treating opioid addiction is their responsibility. Significant barriers remain, including inadequate staff training, lack of access to addiction experts, and perceived efficacy of BMT. Addressing these barriers may lower resistance to buprenorphine adoption and increase access to BMT in rural areas.

PMID: 25651434 [PubMed - as supplied by publisher]

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Pharmacokinetics of Sustained-Release and Transdermal Buprenorphine in Göttingen Minipigs (Sus scrofa domestica).

Buprenorphine Research (PubMed) - Thu, 02/05/2015 - 8:00am
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Pharmacokinetics of Sustained-Release and Transdermal Buprenorphine in Göttingen Minipigs (Sus scrofa domestica).

J Am Assoc Lab Anim Sci. 2014;53(6):692-699

Authors: Thiede AJ, Garcia KD, Stolarik DF, Ma J, Jenkins GJ, Nunamaker EA

Abstract
The opioid buprenorphine has been shown to provide adequate postoperative analgesia in both companion and laboratory animals. However, its use is still hindered by the need for multiple parenteral injections to achieve continuous analgesia. The purpose of the current study was to conduct a pharmacokinetic analysis of 2 new long-acting formulations of buprenorphine-an injectable sustained-release buprenorphine (SRB) and a transdermal buprenorphine (TDB) patch-in healthy Göttingen minipigs by using liquid chromatography-electrospray ionization-tandem mass spectrometry. Administration of 0.18 mg/kg SC SRB and 30 μ g/h TDB achieved AUC0-Tlast of 221.6 ± 26.8 and 25.2 ± 3.9 ng × h/mL, respectively, compared with 9.7 ± 1.4 ng*h/mL for 0.02 mg/kg IV buprenorphine. By using a hypothesized therapeutic plasma buprenorphine concentration threshold of 0.1 ng/mL, therapeutic concentrations were achieved at the first study time point (5 to 30 min) and lasted an average of 8.0 ± 1.3 h for intravenous buprenorphine and 264.0 ± 32.2 h for SRB. TDB achieved therapeutic concentrations in 12 to 24 h after patch application, which lasted until the patch was removed at 72 h. The results of this study suggest that SRB and TDB are long-acting alternatives for pain management, and their use could decrease animal handling and stress, thereby simplifying pain management and improving welfare in laboratory swine.

PMID: 25650977 [PubMed - as supplied by publisher]

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Atipamezole Reverses Ketamine-Dexmedetomidine Anesthesia without Altering the Antinociceptive Effects of Butorphanol and Buprenorphine in Female C57BL/6J Mice.

Buprenorphine Research (PubMed) - Thu, 02/05/2015 - 8:00am
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Atipamezole Reverses Ketamine-Dexmedetomidine Anesthesia without Altering the Antinociceptive Effects of Butorphanol and Buprenorphine in Female C57BL/6J Mice.

J Am Assoc Lab Anim Sci. 2014;53(6):675-683

Authors: Izer JM, Whitcomb TL, Wilson RP

Abstract
Butorphanol and buprenorphine are common analgesics used in laboratory mice. Inadvertent attenuation of the antinociceptive effects of these analgesics via the administration of an anesthetic reversal agent could result in postprocedural pain and distress, with subsequent negative effects on animal welfare, study outcomes, and regulatory compliance. This study was undertaken to determine whether atipamezole reverses ketamine-dexmedetomidine anesthesia and alters the antinociceptive effects of butorphanol and buprenorphine in female C57BL/6J mice. Atipamezole reliably reversed the anesthetic effects of ketamine-dexmedetomidine, and mice were ambulatory 17.4 ± 30.6 min after administration of the α2-adrenoreceptor antagonist. Atipamezole alone had no significant effect on tail-flick latency and did not alter the antinociceptive properties of butorphanol or low-dose (0.05 mg/kg) or high-dose (0.1 mg/kg) buprenorphine in female C57BL/6J mice. After reversal of ketamine-dexmedetomidine anesthesia, tail-flick latency at 30, 60, and 150 min after analgesic treatment differed significantly between mice treated with atipamezole alone and those given atipamezole followed by butorphanol or high-dose buprenorphine. These results suggest that the analgesic effects of butorphanol and buprenorphine are not affected by atipamezole. Buprenorphine (0.1 mg/kg) administered 30 min prior to or at the time of anesthesia resulted in a greater magnitude of antinociception after antagonism of anesthesia than when given at the time of reversal. Given these results, we recommend the use of ketamine-dexmedetomidine anesthesia with buprenorphine administered either preemptively or at the time of anesthetic induction to provide a defined period of surgical anesthesia that is effectively reversed by atipamezole.

PMID: 25650975 [PubMed - as supplied by publisher]

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Primary tumour growth in an orthotopic osteosarcoma mouse model is not influenced by analgesic treatment with buprenorphine and meloxicam.

Buprenorphine Research (PubMed) - Thu, 02/05/2015 - 8:00am
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Primary tumour growth in an orthotopic osteosarcoma mouse model is not influenced by analgesic treatment with buprenorphine and meloxicam.

Lab Anim. 2015 Feb 3;

Authors: Husmann K, Arlt MJ, Jirkof P, Arras M, Born W, Fuchs B

Abstract
Little is known about the treatment of bone pain in animal models of bone cancer. In the present study, the orthotopic 143-B human osteosarcoma xenotransplantation model was used to address the following questions: (1) Can repetitive analgesic treatment extend the experimental period by prolonging the time to reach humane endpoints and (2) Does repetitive analgesic treatment affect bone tumour development and metastasis? The analgesics, buprenorphine and meloxicam, were either applied individually or in combination at 12 h intervals as soon as the animals began to avoid using the tumour cell injected leg. While control mice treated with NaCl showed continuous body weight loss, the major criterion previously for terminating the experiments, animals treated with analgesic substances did not. The control mice had to be sacrificed 26 days after tumour cell injection, whereas the groups of animals with the different pain treatments were euthanized after an additional eight days. Importantly, primary intratibial tumour growth was not affected in any of the experimental groups by any of the pain treatment procedures. Between days 26 and 34 after tumour cell injection an increase of about 100% of the number of lung metastases was found for the groups treated with buprenorphine alone or together with meloxicam, but not for the group treated with meloxicam alone. In summary, the results indicated that both buprenorphine and meloxicam are suitable analgesics for prolonging the experimental periods in an experimental intratibial osteosarcoma mouse model.

PMID: 25650386 [PubMed - as supplied by publisher]

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The Choice of General Anesthetics May Not Affect Neuroinflammation and Impairment of Learning and Memory After Surgery in Elderly Rats.

Buprenorphine Research (PubMed) - Thu, 02/05/2015 - 8:00am
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The Choice of General Anesthetics May Not Affect Neuroinflammation and Impairment of Learning and Memory After Surgery in Elderly Rats.

J Neuroimmune Pharmacol. 2015 Feb 4;

Authors: Zhang J, Tan H, Jiang W, Zuo Z

Abstract
Postoperative cognitive dysfunction (POCD) often occurs in elderly patients and may involve neuroinflammation. This study was to determine whether anesthetic choice (intravenous vs. volatile anesthetics) affects cognitive impairment and neuroinflammation in elderly rat. Total 54 twenty-month old male Fischer 344 rats were assigned randomly to control, right carotid exposure under propofol-buprenorphine or isoflurane-buprenorphine anesthesia groups. They were tested by Barnes maze and fear conditioning from 6 days after the surgery. Their brains were harvested 24 h after the surgery for quantifying interleukin (IL) 1β, tumor necrosis factor (TNF)α and ionized calcium binding adaptor molecule 1 (Iba-1). We showed that the heart rates and mean arterial blood pressure were similar during surgery under propofol-buprenorphine or isoflurane-buprenorphine anesthesia. There was no difference in the surgery-induced increase of the plasma IL-1β and TNFα levels under these two types of anesthesia. Rats subjected to surgery took longer than control rats to identify the target hole 8 days after the completion of training sessions in Barnes maze [32 ± 23 s for control, 118 ± 64 s for propofol group (P < 0.05 vs. control), 107 ± 64 s for isoflurane group (P < 0.05 vs. control)] and had less freezing behavior in the fear conditioning test. Surgery and anesthesia increased IL-1β and Iba-1 but did not affect tau phosphorylated at S199/202 and S396 in the cerebral cortex and hippocampus. Our results suggest that surgery under general anesthesia induces neuroinflammation and cognitive impairment. Anesthetic choice may not be a significant modifiable factor for these effects.

PMID: 25649847 [PubMed - as supplied by publisher]

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Drug-drug Interaction Profile of the All-Oral Anti-Hepatitis C Virus Regimen of Paritaprevir/Ritonavir, Ombitasvir and Dasabuvir.

Buprenorphine Research (PubMed) - Wed, 02/04/2015 - 9:00am
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Drug-drug Interaction Profile of the All-Oral Anti-Hepatitis C Virus Regimen of Paritaprevir/Ritonavir, Ombitasvir and Dasabuvir.

J Hepatol. 2015 Jan 31;

Authors: Menon R, Badri P, Wang T, Polepally A, Zha J, Khatri A, Wang H, Hu B, Coakley E, Podsadecki T, Awni W, Dutta S

Abstract
BACKGROUND AND AIM: Paritaprevir (administered with ritonavir, PTV/r), ombitasvir (OBV), and dasabuvir (DSV) are direct-acting antiviral agents (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection. Thirteen studies were conducted to characterize drug-drug interactions for the 3D regimen of OBV, PTV/r, and DSV and various medications in healthy volunteers to inform dosing recommendations in HCV-infected patients.
METHODS: Mechanism-based drug-drug interactions were evaluated for gemfibrozil, ketoconazole, carbamazepine, warfarin, omeprazole, digoxin, pravastatin, and rosuvastatin. Drug-drug interactions with medications commonly used in HCV-infected patients were evaluated for amlodipine, furosemide, alprazolam, zolpidem, duloxetine, escitalopram, methadone, buprenorphine/naloxone, and oral contraceptives. Ratios of geometric means with 90% confidence intervals for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were used to determine the magnitude of interaction.
RESULTS: Coadministration with the 3D regimen of OBV, PTV/r, and DSV resulted in a < 2-fold change in mean Cmax and AUC for most medications and the DAAs, indicating minimal to modest interactions. Carbamazepine decreased PTV, ritonavir, and DSV exposures substantially, while gemfibrozil increased DSV exposures substantially. Although coadministration with ethinyl estradiol-containing contraceptives resulted in elevated alanine aminotransferase levels, coadministration with a progestin-only contraceptive did not.
CONCLUSIONS: The majority of medications can be coadministered with the 3D regimen of OBV, PTV/r, and DSV without dose adjustment, or with clinical monitoring or dose adjustment. Although no dose adjustment is necessary for the 3D regimen when coadministered with 17 of the 20 medications, coadministration with gemfibrozil, carbamazepine, or ethinyl estradiol-containing contraceptives is contraindicated.

PMID: 25646891 [PubMed - as supplied by publisher]

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Fatal poisoning in drug addicts in the Nordic countries in 2012.

Buprenorphine Research (PubMed) - Wed, 02/04/2015 - 9:00am
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Fatal poisoning in drug addicts in the Nordic countries in 2012.

Forensic Sci Int. 2015 Jan 13;248C:172-180

Authors: Simonsen KW, Edvardsen HM, Thelander G, Ojanperä I, Thordardottir S, Andersen LV, Kriikku P, Vindenes V, Christoffersen D, Delaveris GJ, Frost J

Abstract
This report is a follow-up to a study on fatal poisoning in drug addicts conducted in 2012 by a Nordic working group. Here we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on sex, number of deaths, places of death, age, main intoxicants and other drugs detected in the blood were recorded. National data are presented and compared between the Nordic countries and with data from similar studies conducted in 1991, 1997, 2002 and 2007. The death rates (number of deaths per 100,000 inhabitants) increased in drug addicts in Finland, Iceland and Sweden but decreased in Norway compared to the rates in earlier studies. The death rate was stable in Denmark from 1991 to 2012. The death rate remained highest in Norway (5.79) followed by Denmark (5.19) and Iceland (5.16). The differences between the countries diminished compared to earlier studies, with death rates in Finland (4.61) and Sweden (4.17) approaching the levels in the other countries. Women accounted for 15-27% of the fatal poisonings. The median age of the deceased drug addicts was still highest in Denmark, and deaths of addicts >45 years old increased in all countries. Opioids remained the main cause of death, but medicinal opioids like methadone, buprenorphine, fentanyl and tramadol mainly replaced heroin. Methadone was the main intoxicant in Denmark and Sweden, whereas heroin/morphine caused the most deaths in Norway. Finland differed from the other Nordic countries in that buprenorphine was the main intoxicant with only a few heroin/morphine and methadone deaths. Deaths from methadone, buprenorphine and fentanyl increased immensely in Sweden compared to 2007. Poly-drug use was widespread in all countries. The median number of drugs per case varied from 4 to 5. Heroin/morphine, medicinal opioids, cocaine, amphetamines, benzodiazepines and alcohol were the main abused drugs. However, less widely used drugs, like gamma-hydroxybutyric acid (GHB), methylphenidate, fentanyl and pregabalin, appeared in all countries. New psychotropic substances emerged in all countries, with the largest selection, including MDPV, alpha-PVP and 5-IT, seen in Finland and Sweden.

PMID: 25645132 [PubMed - as supplied by publisher]

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