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Validation of a three-item Fatigue Severity Scale for patients with substance use disorder: a cohort study from Norway for the period 2016–2020

Background: Little attention has been paid to customising fatigue questionnaires for patients with Substance Use Disorders (SUDs). The present study aims to validate and shorten the nine-item Fatigue Severity Scale (FSS-9) and Visual Analogue Fatigue Scale (VAFS) for use with this population. Methods: We used data from a nested cohort with annual health assessments with responses on the FSS-9 and VAFS. During the period 2016–2020, 917 health assessments were collected from 655 patients with SUD in Bergen and Stavanger, Norway. A total of 225 patients answered the health assessment at least twice. We defined baseline as the first annual health assessment when the health assessments were sorted chronologically per patient. We checked for internal consistency, and we used longitudinal confirmatory factor analysis (CFA) and linear mixed model (LMM) analysis to validate and shorten the FSS-9 and VAFS. Results: The internal consistency of the FSS-9 was excellent with a Cronbach’s α of 0.94 at baseline and 0.93 at the second annual health assessment. When shortening the FSS-9 to a three-item FSS (FSS-3, items 5–7), the Cronbach’s α was 0.87 at baseline and 0.84 at the second health assessment. The internal consistency was not affected when the VAFS was added to the FSS-3 and the FSS-9. The longitudinal CFA model showed a well-fitting model for the FSS-3 (χ2 = 13.33, degree of freedom = 8, P = 0.101). The LMM analysis showed equal linear changes at the individual level for the FSS-3 (slope: 0.00, P > 0.05) and FSS-9 (slope: 0.01, P > 0.05) between the health assessments. Conclusion: The FSS-9 could be shortened to the FSS-3 with high validity and reliability for patients with SUDs and the addition of VAFS did not provide much added variability.publishedVersio

Changes in substance use during outpatient treatment for substance use disorders: a prospective Norwegian cohort study from 2016 to 2020

Background Continuous use of amphetamines, alcohol, benzodiazepines, cannabis, cocaine, or opioids contributes to health impairments, increased morbidity, and overdose deaths among patients with substance use disorders (SUDs). This study evaluates the impact of inpatient detoxification, injecting substance use, age, and gender on substance use over time among patients undergoing outpatient SUD treatment. Methods We used data from a cohort of SUD patients in Norway obtained from health assessments of self-reported substance use and sociodemographic and clinical factors. A total of 881 substance use measurements, including substances and frequency of use, were assessed for 708 SUD patients in 2016–2020. Of those, 171 patients provided two or more substance use measurements. The total substance use was calculated, creating a substance use severity index (SUSI), ranging from zero (no use) to one (daily use of all substances). We defined baseline as the first substance use measurement when the measurements were listed chronologically. Time was defined as years from baseline. We used a linear mixed model to analyze the SUSI at baseline and over time, and its associations with inpatient detoxification, injecting substance use, gender, and age, presented with coefficients and 95% confidence intervals (CI). Results No longitudinal changes in the SUSI were found compared with baseline (change in SUSI (cSUSI): 0.04, 95% CI: − 0.05;0.13, p = 0.397). Likewise, “inpatient detoxification” was not associated with changes in the SUSI compared with “no inpatient detoxification” (cSUSI: 0.00, 95% CI: − 0.04;0.04, p = 0.952). However, injecting substances were associated with a higher SUSI than not injecting substances at baseline (difference in SUSI: 0.19, 95% CI: 0.16;0.21, p = < 0.001), and starting to inject substances was associated with increasing SUSI over time compared with not starting to inject substances (cSUSI: 0.11, 95% CI: 0.07;0.15, p = < 0.001). Gender was not significantly associated with changes in the SUSI (cSUSI: − 0.04, 95% CI: − 0.07;0.00, p = 0.052), while patients over 60 years of age had a lower SUSI than those under the age of 30 at baseline (difference in SUSI: − 0.08, 95% CI: − 0.14;− 0.01, p = 0.018), with no change over time (cSUSI: − 0.05, 95% CI: − 0.16;0.05, p = 0.297). Conclusion The present study demonstrates that inpatient detoxification was not associated with substance use changes over time for patients undergoing outpatient SUD treatment. Otherwise, injecting substance use was a particular risk factor for a high level of substance use. Future research needs to evaluate the impact of other treatment approaches on substance use, ideally in randomized controlled trials.publishedVersio

Vitamin D status and associations with substance use patterns among people with severe substance use disorders in Western Norway

Chronic and harmful substance use is associated with a cluster of harms to health, including micronutrient deficiencies. Maintaining adequate levels of vitamin D is important for musculoskeletal and other aspects of health. In this prospective longitudinal cohort study, 666 participants drawn from outpatient opioid agonist therapy (OAT) clinics and community care clinics for substance use disorder in Western Norway were assessed annually for determination of serum 25-hydroxyvitamin D [s-25(OH)D] levels. Fifty-seven percent were deficient at baseline (s-25(OH)D < 50 nmol/l), and 19% were severely deficient (s-25(OH)D < 25 nmol/l). Among those deficient/severely deficient at baseline, 70% remained deficient/severely deficient at the last measurement (mean duration 714 days). Substance use patterns and dosage of opioids for OAT were not associated with vitamin D levels. One exception was found for cannabis, where consumption on a minimum weekly basis was associated with lower levels at baseline (mean difference: −5.2 nmol/l, 95% confidence interval [CI]: −9.1, − 1.3), but without clear time trends (mean change per year: 1.4 nmol/l, CI: − 0.86, 3.7). The high prevalence of sustained vitamin D deficiency in this cohort highlights the need for targeted monitoring and supplementation for this and similar at-risk populations.publishedVersio

Dispensations of benzodiazepines, zhypnotics, and gabapentinoids to patients receiving opioid agonist therapy; a prospective cohort study in Norway from 2013 to 2017

Background Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients on opioid agonist therapy (OAT) are common and have pros and cons. The objectives of the current study are to define the dispensation rates of these potentially addictive drugs, and whether the number and the mean daily doses of dispensed OAT opioids and discontinuing OAT, are associated with being dispensed benzodiazepines, z-hypnotics and gabapentinoids among patients on OAT in Norway in the period 2013 to 2017. Methods Information about all dispensed opioids, benzodiazepines, z-hypnotics and gabapentinoids were recorded from the Norwegian Prescription Database (NorPD). A total of 10,371 OAT patients were included in the study period. The dispensation rates were defined as the number of patients who were dispensed at least one of the potentially addictive drugs divided among the number of patients who have dispensed an OAT opioid per calendar year. Mean daily doses were calculated, and for benzodiazepines and z-hypnotics, stated in diazepam equivalents. The association between dispensed potentially addictive drugs, and the number and the type of dispensed OAT opioids were calculated by using logistic regression models. Results Half of the OAT patients received at least one dispensation of a benzodiazepine or z-hypnotic, and 11% were dispensed at least a gabapentinoid in 2017. For dispensed benzodiazepines or z-hypnotics, the mean daily dose was reduced from 21 mg (95% confidence interval (CI): 20–23) diazepam equivalents in 2013 to 17 mg (95% CI: 16–17) in 2017. The mean daily dose of pregabalin increased from 365 mg (95% CI: 309–421) in 2013 to 386 mg (95% CI: 349–423) in 2017. Being dispensed a gabapentinoid (adjusted odds ratio (aOR) = 2.5, 95% CI: 2.1–3.0) or a non-OAT opioid (aOR = 3.0, 95% CI: 2.6–3.5) was associated with being dispensed a benzodiazepine or z-hypnotic. Discontinuing OAT did not affect the number of dispensations and the doses of potentially addictive drugs. Conclusion The dispensation rates of potentially addictive drugs are high in the OAT population. Treatment indications, as well as requirements for prescription authority, need to be debated and made explicit. Randomized controlled trials evaluating the benefits and risks of such co-prescription are required.publishedVersio

Emotional Eating and Changes in High-Sugar Food and Drink Consumption Linked to Psychological Distress and Worries: A Cohort Study from Norway

Psychological distress is linked to unhealthy eating behaviors such as emotional eating and consumption of high-sugar food and drinks. Cross-sectional studies from early in the COVID-19 pandemic showed a high occurrence of worries and psychological distress, and this was associated with emotional eating. Few larger studies have examined how this coping pattern develops over time. This cohort study with 24,968 participants assessed changes over time in emotional eating, consumption of sugary foods as an example of unhealthy food choices, and consumption of fruits and vegetables as an example of healthy food choices. Further, associations between these and psychological distress, worries, and socio-demographic factors were assessed. Data were collected at three time points (April 2020, initially in the COVID-19 pandemic, then one and two years later). Emotional eating and intake of sugary foods and drinks were high at the start of the pandemic, followed by a reduction over time. High psychological distress was strongly associated with higher levels of emotional eating and high-sugar food intake, and lower levels of healthy eating habits. The strength of this association reduced over time. Our findings indicate the high frequency in unhealthy food choices seen early in the COVID-19 pandemic improved over time.publishedVersio

The association between psychological distress and alcohol consumption and physical activity: a population-based cohort study

Introduction: The COVID-19 pandemic and infection control measures caused changes to daily life for most people. Heavy alcohol consumption and physical inactivity are two important behavioral risk factors for noncommunicable diseases worldwide. The COVID-19 pandemic, with its social distancing measures, home office policies, isolation, and quarantine requirements may have an impact on these factors. This three-wave longitudinal study aims to investigate if psychological distress and worries related to health and economy were associated with levels and changes in alcohol consumption and physical activity during the two first years of the COVID-19 pandemic in Norway. Methods: We used data collected in April 2020, January 2021, and January 2022 from an online longitudinal population-based survey. Alcohol consumption and physical activity status were assessed at all three measuring points via the Alcohol Use Disorder Identification Test (AUDIT-C) and the International Physical Activity Questionnaire (IPAQ-SF). COVID-19-related worries, home office/study, occupational situation, age, gender, children below 18 years living at home, and psychological distress (measured with the Symptom Checklist (SCL-10)) were included as independent variables in the model. A mixed model regression was used and presented with coefficients with 95% confidence intervals (CI). Results: Analysis of data from 25,708 participants demonstrates that participants with substantial symptoms of psychological distress more often reported higher alcohol consumption (1.86 units/week, CI 1.48–2.24) and lower levels of physical activity [−1,043 Metabolic Equivalents of Task (METs) per week, CI −1,257;−828] at baseline. Working/studying from home (0.37 units/week, CI 0.24–0.50) and being male (1.57 units/week, CI 1.45–1.69) were associated with higher alcohol consumption. Working/studying from home (−536 METs/week, CI −609;−463), and being older than 70 years (−503 METs/week, CI −650;−355) were related to lower levels of physical activity. The differences in activity levels between those with the highest and lowest levels of psychological distress reduced over time (239 METs/week, CI 67;412), and similarly the differences in alcohol intake reduced over time among those having and not having children < 18 years (0.10 units/week, CI 0.01–0.19). Conclusion: These findings highlight the substantial increases in risks related to inactivity and alcohol consumption among those with high levels of psychological distress symptoms, and particularly during the COVID-19 pandemic, and increase the understanding of factors associated with worries and health behavior.publishedVersio

On the path towards universal coverage of hepatitis C treatment among people receiving opioid agonist therapy (OAT) in Norway: A prospective cohort study from 2013 to 2017

Objectives We aimed to calculate cumulative hepatitis C virus (HCV) treatment coverage among individuals enrolled in opioid agonist therapy (OAT) in Norway between 2013 and 2017 and to document the treatment transition to direct-acting antiviral (DAA) agents. Moreover, we aimed to describe adherence to DAAs in the same cohort. Design Prospective cohort, registry data. Setting Specialist healthcare service (secondary) Participants and outcomes This observational study was based on data from The Norwegian Prescription Database. We studied dispensed OAT and HCV treatment annually to calculate the cumulative frequency, and employed secondary sources to calculate prevalence, incidence and HCV treatment coverage from 2013 to 2017, among the OAT population. Factors associated with adherence to DAAs were identified a priori and subject to logistic regression. Results 10 371 individuals were identified with dispensed OAT, 1475 individuals of these were identified with dispensed HCV treatment. Annual HCV treatment coverage increased from 3.5% (95% CI: 3.2 to 4.4) in 2013 to 17% (95% CI: 17 to 20) in 2017, giving a cumulative HCV coverage among OAT patients in Norway of 38.5%. A complete shift to interferon-free treatment regimens occurred, where DAAs accounting for 32% of HCV treatments in 2013 and 99% in 2017. About two-thirds of OAT patients were considered adherent to their DAA regimens across all genotypes. High level of OAT continuity was associated with improved adherence to DAAs (adjusted OR 1.4, 95% CI: 1 to 2, p=0.035). Conclusions A large increase in HCV treatment coverage attributed by a complete shift to interferon-free regimens among the Norwegian OAT population has been demonstrated. However, treatment coverage is inadmissibly too low and a further substantial scale-up in HCV treatment is required to reach the universal targets of controlling and eliminating the HCV endemic.publishedVersio

Effect of fruit smoothie supplementation on psychological distress among people with substance use disorders receiving opioid agonist therapy: protocol for a randomised controlled trial (FruktBAR)

Background: People with substance use disorders generally have unhealthy diets, including limited intake of fruit and vegetables. Evidence shows substantial health benefits from increasing fruit and vegetable consumption on various indicators and possibly also psychological distress. A pilot study has indicated that supplementation with fruit smoothie could be promising also among people receiving opioid agonist therapy for opioid dependence. FruktBAR will compare the efficacy of added fruit smoothie supplementation to people receiving opioid agonist therapy compared to standard treatment without added supplementation. Methods: FruktBAR is a multicentre, randomised controlled trial. The trial will aim to recruit 302 patients receiving opioid agonist therapy. The intervention involves daily supplementation with 250 ml fruit smoothie including a variety of fruits such as apple, pineapple, mango, bananas, orange, blueberries, passion fruit, coconut, lime, and blackcurrant. The main endpoints are 16 weeks after intervention initiation. Participants will be included and followed up during and after the intervention. The target group will be patients with opioid dependence receiving opioid agonist therapy from involved outpatient clinics in Bergen and Stavanger, two of the largest cities in Norway. The main outcome is psychological distress assessed with Hopkins Symptom Checklist (SCL-10) at the end of the intervention period 16 weeks after initiation, and will be compared between the intervention and control arms. Secondary outcome measures are changes in fatigue, physical functioning assessed with a 4-minute step-test, health-related quality of life, biochemical indicators of inflammation, and biochemical indicators of fruit intake. Discussion: This study will inform on the relative advantages or disadvantages of fruit supplementation in addition to the current medically and psychologically oriented treatment of people receiving opioid agonist therapy. If the supplementation is efficacious, it can be considered for further scale-up.publishedVersio

Impact of liver fibrosis and clinical characteristics on dose-adjusted serum methadone concentrations

Background There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements. Objectives We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations. Methods We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016–2020. A possible association between the degree of liver fibrosis and dose-adjusted serum methadone concentration was explored using a linear mixed-model analysis. Results When adjusted for age, gender, body mass index, and genotypes of CYP2B6 and CYP3A5, the concentration-to-dose ratio of methadone did not increase among the participants with liver fibrosis (Coefficient: 0.70; 95% CI: −2.16, 3.57; P: 0.631), even among those with advanced cirrhosis (−0.50; −4.59, 3.59; 0.810). Conclusions Although no correlation was found between the degree of liver stiffness and dose-adjusted serum methadone concentration, close clinical monitoring should be considered, especially among patients with advanced cirrhosis. Still, serum methadone measurements can be considered a supplement to clinical assessments, taking into account intra-individual variations.publishedVersio