CYP3A subfamily activity affects the equilibrium concentration of Phenazepam® in patients with anxiety disorders and comorbid alcohol use disorder

2020 ◽  
Vol 21 (7) ◽  
pp. 449-457
Author(s):  
Mikhail Sergeevich Zastrozhin ◽  
Valentin Yurievich Skryabin ◽  
Alexander Sergeevich Sorokin ◽  
Aleksey Evgenievich Petukhov ◽  
Valery Valerievich Smirnov ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Anxiety Disorders ◽  
Alcohol Use Disorder ◽  
Equilibrium Concentration ◽  
Inverse Correlation ◽  
Cyp3a Activity ◽  
Dose Ratio ◽  
Significant Inverse Correlation ◽  
Safety And Efficacy ◽  
Cortisol Ratio

Phenazepam® is prescribed to relieve anxiety and sleep disorders during alcohol withdrawal, although it is associated with undesirable side effects. Aim: To demonstrate changes in the safety and efficacy profiles of Phenazepam in patients with anxiety disorders and comorbid alcohol use disorder. Materials & methods: A total of 94 Russian patients with alcohol use disorder received 4.0 mg of Phenazepam per day in tablets. We used a urinary 6-beta-hydroxycortisol/cortisol ratio to evaluate CYP3A activity. Results: A statistically significant inverse correlation between Phenazepam plasma concentration and CYP3A activity was found (r = -0.340 and p = 0.017). Correlation between the concentration/dose ratio and phenotyping results was also statistically significant (r = 0.301 and p = 0.026). Conclusion: The safety and efficacy of Phenazepam depend on CYP3A genetic polymorphisms.

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

2019 ◽  
Vol 97 (8) ◽  
pp. 781-785 ◽  
Author(s):  
M.S. Zastrozhin ◽  
V.Y. Skryabin ◽  
V.V. Smirnov ◽  
E.A. Grishina ◽  
K.A. Ryzhikova ◽  
...  
Keyword(s):  
Alcohol Use ◽  
High Performance ◽  
Alcohol Use Disorder ◽  
Depressive Disorders ◽  
Rating Scale ◽  
Correlation Coefficients ◽  
Inverse Correlation ◽  
Efficacy And Safety ◽  
Cyp2d6 Activity ◽  
Scale Scores

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 < 0.001), and for the The UKU Side Effects Rating Scale (UKU): (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p < 0.001). The calculation of correlation coefficients between the differences in scale scores and metabolic rate showed the presence of statistically significant weak inverse correlation with the efficacy indicator evaluated by HAMD (r = −0.278, p < 0.05), but not by UKU (r = 0.274, p > 0.05). This study demonstrated that an increased CYP2D6 activity reduces the efficacy of treatment with mirtazapine.

scholarly journals Shared genetic factors influence risk for bipolar disorder and alcohol use disorders

2014 ◽  
Vol 29 (5) ◽  
pp. 282-287 ◽  
Author(s):  
N. Carmiol ◽  
J.M. Peralta ◽  
L. Almasy ◽  
J. Contreras ◽  
A. Pacheco ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Alcohol Use ◽  
Anxiety Disorders ◽  
Nicotine Dependence ◽  
Alcohol Use Disorder ◽  
Genetic Factors ◽  
Alcohol Use Disorders ◽  
Costa Rican ◽  
High Rate ◽  
Shared Genetic

AbstractBipolar disorder and alcohol use disorder (AUD) have a high rate of comorbidity, more than 50% of individuals with bipolar disorder also receive a diagnosis of AUD in their lifetimes. Although both disorders are heritable, it is unclear if the same genetic factors mediate risk for bipolar disorder and AUD. We examined 733 Costa Rican individuals from 61 bipolar pedigrees. Based on a best estimate process, 32% of the sample met criteria for bipolar disorder, 17% had a lifetime AUD diagnosis, 32% met criteria for lifetime nicotine dependence, and 21% had an anxiety disorder. AUD, nicotine dependence and anxiety disorders were relatively more common among individuals with bipolar disorder than in their non-bipolar relatives. All illnesses were shown to be heritable and bipolar disorder was genetically correlated with AUD, nicotine dependence and anxiety disorders. The genetic correlation between bipolar and AUD remained when controlling for anxiety, suggesting that unique genetic factors influence the risk for comorbid bipolar and AUD independent of anxiety. Our findings provide evidence for shared genetic effects on bipolar disorder and AUD risk. Demonstrating that common genetic factors influence these independent diagnostic constructs could help to refine our diagnostic nosology.

Genotyping and phenotyping of CYP2D6 and CYP3A isoenzymes in patients with alcohol use disorder: correlation with haloperidol plasma concentration

2017 ◽  
Vol 32 (3) ◽  
Author(s):  
Dmitry A. Sychev ◽  
Mikhail S. Zastrozhin ◽  
Igor I. Miroshnichenko ◽  
Natalia V. Baymeeva ◽  
Valery V. Smirnov ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Equilibrium Concentration ◽  
Primary Objective ◽  
Plasma Drug ◽  
Metabolism Rate ◽  
Genes Encoding ◽  
Allele Specific ◽  
Male Patients ◽  
Contradictory Data

AbstractBackground:Haloperidol is used for the treatment of alcohol use disorders in patients with signs of alcohol-related psychosis. Haloperidol therapy poses a high risk of adverse drug reactions (ADR). Contradictory data, which include the effects of genetic polymorphisms in genes encoding the elements of haloperidol biotransformation system on haloperidol metabolism rate and plasma drug concentration ratio, are described in patients with different genotypes. The primary objective of this study was to investigate the effects ofMethods:The study included 69 male patients with alcohol use disorder. Genotyping was performed using the allele-specific real-time PCR.Results:Results indicated that both C/D indexes and equilibrium concentration levels depend onConclusions:The study demonstrates that

scholarly journals Explaining the association between anxiety disorders and alcohol use disorder: A twin study

2019 ◽  
Vol 36 (6) ◽  
pp. 522-532 ◽  
Author(s):  
Fartein Ask Torvik ◽  
Tom Henrik Rosenström ◽  
Kristin Gustavson ◽  
Eivind Ystrom ◽  
Kenneth S. Kendler ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Anxiety Disorders ◽  
Twin Study ◽  
Alcohol Use Disorder

Agreement between DSM-IV and DSM-5 criteria for alcohol use disorder among outpatients suffering from depressive and anxiety disorders

2016 ◽  
Vol 26 (1) ◽  
pp. 53-56 ◽  
Author(s):  
Francesco Bartoli ◽  
Giuseppe Carrà ◽  
Enrico Biagi ◽  
Cristina Crocamo ◽  
Antonios Dakanalis ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Anxiety Disorders ◽  
Alcohol Use Disorder ◽  
Dsm 5 ◽  
Dsm Iv

DSM-5 alcohol use disorder features among treatment-seeking older adults

2018 ◽  
Vol 64 (4) ◽  
pp. 185-196 ◽  
Author(s):  
Silke Behrendt ◽  
Barbara Braun ◽  
Randi Bilberg ◽  
Gerhard Bühringer ◽  
Michael Bogenschutz ◽  
...  
Keyword(s):  
Older Adults ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
The Elderly ◽  
Treatment Seeking ◽  
Controlled Clinical Trial ◽  
Dsm 5 ◽  
Wide Range ◽  
And Gender ◽  
International Multicenter

Abstract. Background: The number of older adults with alcohol use disorder (AUD) is expected to rise. Adapted treatments for this group are lacking and information on AUD features in treatment seeking older adults is scarce. The international multicenter randomized-controlled clinical trial “ELDERLY-Study” with few exclusion criteria was conducted to investigate two outpatient AUD-treatments for adults aged 60+ with DSM-5 AUD. Aims: To add to 1) basic methodological information on the ELDERLY-Study by providing information on AUD features in ELDERLY-participants taking into account country and gender, and 2) knowledge on AUD features in older adults seeking outpatient treatment. Methods: baseline data from the German and Danish ELDERLY-sites (n=544) were used. AUD diagnoses were obtained with the Mini International Neuropsychiatric Interview, alcohol use information with Form 90. Results: Lost control, desired control, mental/physical problem, and craving were the most prevalent (> 70 %) AUD-symptoms. 54.9 % reported severe DSM-5 AUD (moderate: 28.2 %, mild: 16.9 %). Mean daily alcohol use was 6.3 drinks at 12 grams ethanol each. 93.9 % reported binging. More intense alcohol use was associated with greater AUD-severity and male gender. Country effects showed for alcohol use and AUD-severity. Conclusion: European ELDERLY-participants presented typical dependence symptoms, a wide range of severity, and intense alcohol use. This may underline the clinical significance of AUD in treatment-seeking seniors.

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