Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder

The objective of the study was to investigate the effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder who received mirtazapine. The study included 109 Russian patients who received mirtazapine at a dose of 30.0 [15.0; 45.0] mg per day. Genotyping of CYP2D6*4 (1846G > A, rs3892097) was performed using real-time polymerase chain reaction with allele-specific hybridization. The activity of CYP2D6 was evaluated by determining the concentration of endogenous substrate of the enzyme and its urinary metabolite — pinoline to 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline ratio, using high-performance liquid chromatography – mass spectrometry. The statistically significant differences between the scores on the Hamilton Depression Rating Scale (HAMD) in patients with different genotypes were revealed by day 16: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.2] (p 0.05). This study demonstrated that an increased CYP2D6 activity reduces the efficacy of treatment with mirtazapine.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

How do CYP2C19*2 and CYP2C19*17 genetic polymorphisms affect the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome?

© 2020 Walter de Gruyter GmbH, Berlin/Boston.Background: Diazepam is one of the most commonly prescribed tranquilizers for therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on its efficacy and safety. The objective of our study was to investigate the effect of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy and safety of diazepam in patients with AWS. Methods: The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 681G>A (CYP2C19*2, rs4244285) genotypes: (CYP2C19*1/*1) -8.5 [-15.0; -5.0], (CYP2C19*1/*2 and CYP2C19*2/*2) -12.0 [-13.0; -9.0], p = 0.021. The UKU scale scores, which were used to evaluate the safety of therapy, were also different: (CYP2C19*1/*1) 7.0 [6.0; 12.0], (CYP2C19*1/*2 and CYP2C19*2/*2) 9.5 [8.0; 11.0], p = 0.009. Patients carrying different CYP2C19 -806C>T (CYP2C19*17, rs12248560) genotypes also demonstrated differences in therapy efficacy and safety rates. Conclusions: Thus, the effects of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy of diazepam were demonstrated.info:eu-repo/semantics/publishedVersio

The Association between the Alcohol Biomarker Phosphatidylethanol (PEth) and Self-Reported Alcohol Consumption among Russian and Norwegian Medical Patients

Abstract Aims Valid measures to identify harmful alcohol use are important. Alcohol Use Disorders Identification Test (AUDIT) is a validated questionnaire used to self-report harmful drinking in several cultures and settings. Phosphatidylethanol 16:0/18:1 (PEth) is a direct alcohol biomarker measuring alcohol consumption levels. The aim of this study was to investigate how PEth levels correlate with AUDIT-QF and weekly grams of alcohol consumed among patients in two urban hospitals. In addition, we wanted to investigate the predictive value of PEth in identifying harmful alcohol use as defined by AUDIT-QF and weekly grams of alcohol cutoffs. Methods A cross-sectional study comprising acute medically ill patients with measurable PEth levels (≥0.030 μM) admitted to two urban hospitals in Oslo, Norway (N = 931) and Moscow, Russia (N = 953) was conducted using PEth concentrations in whole blood, sociodemographic data and AUDIT-QF questionnaires. Results PEth levels from patients with measurable PEth were found to be positively correlated with AUDIT-QF scores, with PEth cutpoints of 0.128 μM (Oslo) and 0.270 μM (Moscow) providing optimal discrimination for harmful alcohol use defined by AUDIT-QF (the difference between cities probably reflecting different national drinking patterns in QF). When converting AUDIT-QF into weekly grams of alcohol consumed, the predictive value of PEth improved, with optimal PEth cutpoints of 0.327 (Oslo) and 0.396 (Moscow) μM discriminating between harmful and non-harmful alcohol use as defined in grams (≥350 grams/week). Conclusions By using PEth levels and converting AUDIT-QF into weekly grams of alcohol it was possible to get an improved rapid and sensitive determination of harmful alcohol use among hospitalized patients

Prevalence of psychoactive substance use among acutely hospitalised patients in Oslo and Moscow: a cross-sectional, observational study

Objectives The use of psychoactive prescription medication is increasing in the general population. This is a cause for concern, particularly among the elderly, where physiological changes related to senescence increase the risk for adverse effects. While previous studies regarding psychoactive substance use have generally been population based, we sought to determine the frequency of such use among acutely hospitalised patients. Setting Two emergency departments (EDs), one in Oslo and one in Moscow, admitting patients to Departments of Internal Medicine. Participants 5583 patients aged ≥18 years participated, distributed evenly between genders and study locations. Patients unable to give informed consent were excluded. The study sites did not admit patients with surgical conditions and/or injuries. Primary and secondary outcomes The presence of psychoactive substances was determined through blood analysis using liquid chromatography-mass spectrometry. Secondary outcomes comprised demographic data (including age, gender, employment and marital status), degree of psychological distress, concurrent alcohol use, and self-reported alcohol, psychoactive drug and illicit substance use. Results 32.3% in Oslo and 12% in Moscow were positive for one or more psychoactive medicinal drugs (benzodiazepines, z-hypnotics, opioids or barbiturates). In Oslo, medicinal drug use was associated with being aged 61 to 70 years (OR 2.40, 95% CI 1.61 to 3.58) compared with 18 to 40 years, and psychological distress (OR 2.61, 95% CI 2.06 to 3.30). In Moscow, psychoactive medicinal drug use was also associated with psychological distress (OR 1.68, 95% CI 1.18 to 2.39), and was less common among patients aged 41 to 60 years (OR 0.62, 95% CI 0.43 to 0.88) than among patients aged 18 to 40 years. Conclusion A significant proportion of admitted patients used one or more psychoactive medicinal drugs, in particular benzodiazepines (Oslo and Moscow) and opiates (Oslo). We suggest formalised screening for inappropriate prescription drug use and increased adherence to clinical prescription guidelines

sj-docx-1-nad-10.1177_14550725231183236 - Supplemental material for Translating and adapting the Alcohol Use Disorders Identification Test (AUDIT) for use in the Russian Federation: A multicentre pilot study to inform validation procedures

Supplemental material, sj-docx-1-nad-10.1177_14550725231183236 for Translating and adapting the Alcohol Use Disorders Identification Test (AUDIT) for use in the Russian Federation: A multicentre pilot study to inform validation procedures by Maria Neufeld, Anna Bunova, Eugenia Fadeeva, Alexey Nadezhdin, Elena Tetenova, Konstantin Vyshinsky, Carina Ferreira-Borges, Elena Yurasova, Andrey Allenov and Boris Gornyi in Nordic Studies on Alcohol and Drugs</p

sj-docx-2-nad-10.1177_14550725231183236 - Supplemental material for Translating and adapting the Alcohol Use Disorders Identification Test (AUDIT) for use in the Russian Federation: A multicentre pilot study to inform validation procedures

Supplemental material, sj-docx-2-nad-10.1177_14550725231183236 for Translating and adapting the Alcohol Use Disorders Identification Test (AUDIT) for use in the Russian Federation: A multicentre pilot study to inform validation procedures by Maria Neufeld, Anna Bunova, Eugenia Fadeeva, Alexey Nadezhdin, Elena Tetenova, Konstantin Vyshinsky, Carina Ferreira-Borges, Elena Yurasova, Andrey Allenov and Boris Gornyi in Nordic Studies on Alcohol and Drugs</p