Potentially addictive substances among patients in opioid agonist therapy : - dispensations, use, and fatigue -
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Background The current opioid epidemic is a major cause of suffering and overdose deaths globally. It can interact with patients’ general well-being and causes fatigue. Opioid agonist therapy (OAT) is a well-documented effective treatment for patients with severe opioid dependence. It protects against opioid overdose deaths and harms from injecting opioids. Over the past decade, reports from several countries indicate a high prevalence of other potentially addictive substances, involving benzodiazepines, z-hypnotics, gabapentinoids, centrally acting stimulants, and opioids, used alongside dispensed OAT opioids. Although potentially addictive substances may increase the risk of fatal and non-fatal overdoses, they can also be essential in treating underlying mental and physical disorders. No studies have evaluated the extent of all potentially addictive substances for the OAT population in Norway and Sweden and how they affect patients’ self-reported feeling of fatigue. Methods This thesis consists of four papers. Papers I-II evaluated the dispensation rates and dispensed doses of benzodiazepines or z-hypnotics, gabapentinoids, and medications used for attention deficit hyperactivity disorder (ADHD) for 10,371 OAT patients in Norway in 2013-2017 using the Norwegian Prescription Database (NorPD). Paper III compared dispensation rates and dispensed doses of benzodiazepines, z-hypnotics, gabapentinoids, centrally acting substances, strong non-OAT opioids, weak non-OAT opioids among 7176 Norwegian OAT patients and 3591 Swedish OAT patients using data from the NorPD and the Swedish Prescribed Drug Register (SPDR) from 2015 to 2017. The aim of paper IV was three-folded; 1) investigating the extent of some non-dispensed potentially addictive substances (benzodiazepines/z-hypnotics, stimulant substances (amphetamines and cocaine), and opioids), cannabis, and alcohol, 2) measuring fatigue using the nine-item Fatigue Severity Scale (FSS-9), and 3) evaluating how the non-dispensed potentially addictive substances, cannabis, and alcohol were associated with fatigue among substance use disorder (SUD) patients in Bergen and Stavanger, Norway. We defined frequent use of a non-dispensed substance, cannabis, or alcohol as those using a substance at least weekly during the past 12 months. Patients who did not use substances/cannabis/alcohol or use them less than weekly during the past 12 months were categorized as having ‘no frequent use’ of these substances. To reduce confounding between substance use and fatigue, we adjusted for various sociodemographic and clinical factors. We included 954 FSS-9 measurements from 654 SUD patients, involving 82 % OAT patients, using the INTRO-HCV cohort data in 2016-2020. Results In papers I-III, 59 % of the Norwegian OAT patients and 55 % of the Swedish OAT patients were dispensed potentially addictive substances in 2017. In Norway, 46 % of the OAT patients were dispensed a benzodiazepine, 14 % a z-hypnotic, 12 % a weak non-OAT opioid, 10 % a gabapentinoid, 6 % a strong non-OAT opioid, and 4 % a centrally acting stimulant. Among the Swedish OAT population, 26 % were dispensed a z-hypnotic, 19 % a gabapentinoid, 18 % a centrally acting stimulant, 15 % a benzodiazepine, 10 % a strong non-OAT opioid, and 5 % a weak non-OAT opioid. Besides centrally acting stimulants, the mean daily dosages of the dispensed substances were within recommendations. The mean daily dosages of four out of five substances slightly exceeded the recommendations for centrally acting stimulants. Substantial similar results were seen for the period 2013-2016. In addition, being dispensed one benzodiazepine, z-hypnotic, gabapentinoid, non-OAT opioid, or centrally acting stimulant increased the odds of being dispensed several potentially addictive substances. The use of non-dispensed potentially addictive substances, cannabis, and alcohol for SUD patients, mainly OAT patients, in Bergen and Stavanger was substantial. Fifty-two percents were frequent users of cannabis, 39 % benzodiazepines or z-hypnotics, 29 % stimulant substances, 26 % alcohol, and 16 % opioids. Sixty-seven percent of patients exceeded the threshold of severe fatigue (above 36 points). The mean FSS-9 sum score was 43 (standard deviation: 16) on a scale ranging from nine (no fatigue) to 63 points (worst fatigue). A considerable intra-individual variation in fatigue level from first to second fatigue measurement was found. Frequent use of benzodiazepines (adjusted mean difference of FSS-9 sum score: 5.7, 95 % CI: 3.0;8.4) or stimulants (-5.0, -8.0;-2.9) were associated with changes in the FSS-9 sum score compared with less frequent or no use of these substances. Furthermore, females had more fatigue than males (4.1, 1.3;7.0), and having debt difficulties was associated with more fatigue than not having debt difficulties (2.9, 0.4;5.3). In addition, frequent use of benzodiazepines compared with less frequent or no use of these substances over time (-4.4, -8.2;-0.7), and liver fibrosis or cirrhosis compared with healthy liver over time (-5.5, -9.9;-1.0) were associated with slightly less fatigue per year from the first fatigue measurement. Conclusion There was extensive use of different dispensed and non-dispensed potentially addictive substances among OAT patients in Norway and Sweden. In addition, substantial fatigue symptoms were widespread. Considering the high prevalence of polysubstance use in the population, it has been paid relatively little attention to OAT research and national guidelines. Focusing on how polysubstance use can be handled in OAT and its impact on health outcomes is of particular interest in further research.
Has partsPaper I: Vold JH, Skurtveit S, Aas C, Chalabianloo F, Kloster PS, Johansson KA, Fadnes LT: Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients receiving opioid agonist therapy; a prospective cohort study in Norway from 2013 to 2017. BMC health services research 2020, 20(1):352. The article is available at: https://hdl.handle.net/11250/2736871
Paper II: Vold JH, Aas C, Skurtveit S, Odsbu I, Chalabianloo F, Halmøy A, Johansson KA, Fadnes LT: Dispensation of attention deficit hyperactivity disorder (ADHD) medications in patients receiving opioid agonist therapy; a national prospective cohort study in Norway from 2015 to 2017. BMC psychiatry 2020, 20(1):119. The article is available at: https://hdl.handle.net/11250/2730886
Paper III: Vold JH, Aas C, Skurtveit S, Odsbu I, Chalabianloo F, Reutfors J, Halmøy A, Johansson KA, Fadnes LT: Potentially addictive drugs dispensing to patients receiving opioid agonist therapy: a register-based prospective cohort study in Norway and Sweden from 2015 to 2017. BMJ Open 2020, 10(8):e036860. The article is available at: https://hdl.handle.net/11250/2735771
Paper IV: Vold JH, Gjestad R, Aas CF, Chalabianloo F, Skurtveit S, Løberg E-M, Johansson KA, Fadnes LT: Impact of clinical and sociodemographic factors on fatigue among patients with substance use disorder: a cohort study from Norway for the period 2016-2020. Substance Abuse Treat Prev and Policy 2020, 15(1):93. The article is available at: https://hdl.handle.net/11250/2755615