Chemsex in Moscow: investigation of the phenomenon in a cohort of men who have sex with men hospitalized due to addictive disorders

The present study was designed to investigate the phenomenon of chemsex among Moscow men who have sex with men (MSM) patients who were hospitalized due to various addictive disorders. It was an observational cohort study which included a total of 30 male patients who underwent inpatient treatment at the Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare due to various addictive disorders. Data on sociodemographic, sexuality-, sexually transmitted infection- (STI-), and drug use-related characteristics obtained in face-to-face interviews were recorded in all patients. Mean (SD) age of the patients was 24.3 (3.5) years. Mephedrone was the drug most commonly reported as being used for chemsex (over half of cases); it was consumed by 16 patients. Gamma-hydroxybutyric acid/gamma-butyrolactone use was reported by 6.7% of patients; 16.7% of patients preferred cocaine; ketamine use was present only in one patient. Five participants (16.7%) reported the use of other stimulants. Overall, 20% of patients reported their HIV serostatus as positive. Self-reported other STI status was positive in 12 patients (40.0%). Our findings revealed that practicing chemsex among MSM can be considered a trend in Moscow. Our study emphasizes the role of collaborative work of sexologists and addictologists in order to develop and evaluate the interventions. </jats:p

The correlation between CYP2D6 isoenzyme activity and haloperidol efficacy and safety profile in patients with alcohol addiction during the exacerbation of the addiction

Dmitry Alekseevich Sychev,1 Mikhail Sergeevich Zastrozhin,1&ndash;3 Valery Valerieevich Smirnov,4 Elena Anatolievna Grishina,1 Ludmila Mikhailovna Savchenko,1 Evgeny Alekseevich Bryun1,2 1Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation, 2Department of Public Health, Moscow Research and Practical Centre for Narcology, 3Peoples&rsquo; Friendship University of Russia, 4National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia Background: Today, it is proved that isoenzymes CYP2D6 and CYP3A4 are involved in metabolism of haloperidol. In our previous investigation, we found a medium correlation between the efficacy and safety of haloperidol and the activity of CYP3A4 in patients with alcohol abuse.Objective: The aim of this study was to evaluate the correlation between the activity of CYP2D6 and the efficacy and safety of haloperidol in patients with diagnosed alcohol abuse.Methods: The study involved 70 men (average age: 40.83&plusmn;9.92 years) with alcohol addiction. A series of psychometric scales were used in the research. The activity of CYP2D6 was evaluated by high-performance liquid chromatography with mass spectrometry using the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline to pinoline. Genotyping of CYP2D6 (1846G&gt;A) was performed using real-time polymerase chain reaction.Results: According to results of correlation analysis, statistically significant values of Spearman correlation coefficient (rs) between the activity of CYP2D6 and the difference of points in psychometric scale were obtained in patients receiving haloperidol in injection form (Sheehan Clinical Anxiety Rating Scale =-0.721 [P&lt;0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.692 [P&lt;0.001]) and in those receiving haloperidol in tablet form (Covi Anxiety Scale =-0.851 [P&lt;0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.797 [P&lt;0.001]).Conclusion: This study demonstrated the correlations between the activity of CYP2D6 isozyme and the efficacy and safety of haloperidol in patients with alcohol addiction. Keywords: haloperidol, biotransformation, CYP2D6, side effects, alcohol addictio

The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction

Mikhail Sergeevich Zastrozhin,1,2 Elena Anatolievna Grishina,1 Kristina Anatolievna Ryzhikova,1 Valery Valerievich Smirnov,3 Ludmila Mikhailovna Savchenko,1 Evgeny Alekseevich Bryun,1,2 Dmitry Alekseevich Sychev1 1Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, 2Moscow Research and Practical Centre on Addictions, Moscow Department of Healthcare, 3National Research Center Institute of Immunology, Federal Medical-Biological Agency, Moscow, Russia Background: Isoenzymes CYP2D6 and CYP3A4, the activity of which varies widely, are involved in metabolism of haloperidol and may influence its profile of efficacy and safety.Objective: The primary aim of this study was to estimate the relationship between CYP3A5 gene polymorphism, activity of the CYP3A isoenzyme, and the risk of development of adverse drug reactions by haloperidol in patients with alcohol abuse.Methods: Sixty-six male alcohol-addicted patients participated in the study. The safety of haloperidol was evaluated by Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU) and Simpson&ndash;Angus Scale for extrapyramidal symptoms (SAS). The activity of CYP3A was evaluated by determining the concentrations of an endogenous substrate of this isoenzyme (cortisol) and its urinary metabolite (6-beta-hydroxycortisol, 6-B-HC). Genotyping of CYP3A5*3 was performed by real-time polymerase chain reaction with allele-specific hybridization.Results: The frequency of A-allele occurrence in Russian population was very poor (2.27%). CYP3A5*3 polymorphism had no influence on safety profile indicators of haloperidol (UKU scale: p=0.55, SAS scale: p=0.64). In addition, there was no statistical significant difference between the values of indexes of the metabolic ratio (6-B-HC/cortisol) in groups with different genotypes of CYP3A5*3: GG 5.00 (3.36; 6.39) vs AG 5.26 (2.10; 6.78) (p=0.902).Conclusion: The frequency of A-allele occurrence of CYP3A5*3 in Russian population is very poor, and it has no high influence on the safety of haloperidol treatment; therefore, there are no reasons to take this polymorphism into account in patients with alcohol addiction who receive haloperidol. Keywords: haloperidol, CYP3A5*, CYP3A, cortisol, alcohol use disorde

Effects of CYP2D6 genetic polymorphisms on the efficacy and safety of fluvoxamine in patients with depressive disorder and comorbid alcohol use disorder

Mikhail Sergeevich Zastrozhin,1,2 Elena Anatolievna Grishina,3 Nataliya Petrovna Denisenko,3 Valentin Yurievich Skryabin,2 Dmitry Dmitrievich Markov,3 Ludmila Mikhailovna Savchenko,1 Evgeny Alekseevich Bryun,1,2 Dmitry Alekseevich Sychev4 1Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia; 2Department of Addictology, Moscow Research and Practical Center on Addictions, Moscow, Russia; 3Research Centre, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Research Centre, Moscow, Russia; 4Department of Clinical Pharmacology and Therapy, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia Background: Fluvoxamine therapy is used for treatment of patients with depressive disorder, but it is often ineffective, and some patients suffer from dose-dependent undesirable side effects such as vertigo, headache, indigestion, xerostomia, increased anxiety, etc. CYP2D6 is involved in the biotransformation of fluvoxamine. Meanwhile, the genes encoding these isoenzymes have a high level of polymorphism, which may affect the protein synthesis. Objective: The primary objective of our study was to investigate the effects of CYP2D6 genetic polymorphisms on the efficacy and safety of fluvoxamine in patients with depressive disorder and comorbid alcohol use disorder, in order to develop the algorithms of optimization of fluvoxamine therapy for reducing the risk of dose-dependent undesirable side effects and pharmacoresistance. Methods: The study involved 45 male patients (average age: 36.44&plusmn;9.96 years) with depressive disorder and comorbid alcohol use disorder. A series of psychometric scales was used in the research. Genotyping of CYP2D6 (1846G&gt;A) was performed using real-time polymerase chain reaction. Results: According to results of Mann&ndash;Whitney U-test, statistically significant differences between the efficacy and safety of fluvoxamine were obtained on 9th and 16th days of therapy in patients with GG and GA genotypes (The Hamilton Rating Scale for Depression: 10.0 [10.0; 23.0] vs 25.0 [24.0; 16.0] (P&lt;0.001) on the 9th day and 4.0 [2.0; 5.0] vs 6.0 [6.0; 7.0] on the 16th day; The UKU Side Effect Rating Scale: 6.0 [4.0; 6.0] vs 9.0 [9.0; 10.0] (P&lt;0.001) on the 9th day and 5.0 [1.0; 9.0] vs 19.0 [18.0; 22.0] on the 16th day). Conclusion: This study demonstrated the lower efficacy and safety of fluvoxamine in patients with depressive disorder and comorbid alcohol use disorders with GA genotype in CYP2D6 1846G&gt;A polymorphic marker. Keywords: pharmacogenetics, SSRIs, fluvoxamine, biotransformation, personalized medicine, CYP2D6, depressive disorders, alcohol addictio

Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder

Mikhail Sergeevich Zastrozhin,1,2 Vadim Markovich Brodyansky,3 Valentin Yurievich Skryabin,4 Elena Anatolievna Grishina,5 Dmitry Vladimirovich Ivashchenko,5 Kristina Anatolievna Ryzhikova,5 Ludmila Mikhaylovna Savchenko,1 Alexander Olegovich Kibitov,3 Evgeny Alekseevich Bryun,1,4 Dmitry Alekseevich Sychev6 1Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia; 2Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Center for the Prevention of Dependent Behavior, Moscow, Russia; 3Federal Medical Research Centre of Psychiatry and Addictology, Laboratory of Molecular Genetics, Moscow, Russia; 4Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Department of Addictology, Moscow, Russia; 5Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Research Centre, Moscow, Russia; 6Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Department of Clinical Pharmacology and Therapy, Moscow, Russia Background: Antipsychotic action of haloperidol is due to blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptor blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-methyltransferase [COMT], glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane) are described.Objective: The objectives of this study were to evaluate the correlation between DRD2, SLC6A3 (DAT) and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol-use disorder who received haloperidol.Patients and methods: The study included 64 male patients (average age 41.38 &plusmn; 10.14&nbsp;years, median age 40&nbsp;years, lower quintile [LQ] 35&nbsp;years, upper quintile [UQ] 49&nbsp;years). Bio-Rad CFX Manager&trade; software and &ldquo;SNP-Screen&rdquo; sets of &ldquo;Syntol&rdquo; (Russia) were used to determine polymorphisms rs4680, rs1800497, rs1124493, rs2242592, rs2298826 and rs2863170. In every &ldquo;SNP-Screen&rdquo; set, two allele-specific hybridizations were used, which allowed to determine two alleles of studied polymorphism separately on two fluorescence channels.Results: Results of this study detected a statistically significant difference in the adverse drug reaction intensity in patients receiving haloperidol with genotypes 9/10 and 10/10 of polymorphic marker SLC6A3 rs28363170. In patients receiving haloperidol in tablets, the increases in the UKU Side-Effect Rating Scale (UKU) score of 9.96 &plusmn; 2.24 (10/10) versus 13 &plusmn; 2.37 (9/10; p&nbsp;&lt;&nbsp;0.001) and in the Simpson-Angus Scale (SAS) score of 5.04 &plusmn; 1.59 (10/10) versus 6.41 &plusmn; 1.33 (9/10; p = 0.006) were revealed.Conclusion: Polymorphism of the SCL6A3 gene can affect the safety of haloperidol, and this should be taken into account during the choice of drug and its dosage regimen. Keywords: haloperidol, pharmacogenetics, DRD2, COMT, DAT, alcohol addiction, alcohol-use disorde