The Effect of Cyp2d6 Gene Polymorphism on the Efficacy and Safety of Mirtazapine in Patients with Depressive Disorders Comorbid with Alcohol

Cover Page
  • Authors: Zastrozhin M.S.1,2, Smirnov V.V.3,4, Sorokin A.S.1, Grishina E.A.2, Ryzhikova K.A.2, Shipitsyn V.V.1, Savchenko L.M.2, Buzik O.Z.1,2, Koporov S.S.1, Bryun E.A.1,2, Sychev D.A.2
  • Affiliations:
    1. Moscow Research and Practical Centre for Narcology of the Department of Public Health
    2. Russian Medical Academy of Continuous Professional Education
    3. National Research Center-Institute of Immunology Federal Medical-Biological Agency of Russia
    4. I.M. Sechenov First Moscow State Medical University (Sechenov University)
  • Issue: Vol 74, No 3 (2019)
  • Pages: 185-191
  • Section: PSYCHOLOGY AND PSYCHIATRY: CURRENT ISSUES
  • URL: https://vestnikramn.spr-journal.ru/jour/article/view/1075
  • DOI: https://doi.org/10.15690/vramn1075
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Abstract


Background: Alcohol dependence is often combined with affective disorders, in particular, depressive disorder, which adversely affects the prognosis of the course of both diseases. For the treatment of a depressive disorder, drugs from the group of tetracyclic antidepressants, of which mirtazapine is a representative, are used. Therapy with mirtazapine is associated with the risk of undesirable drug reactions and pharmacoresistance. Aim: To study the effect of CYPD6 isoenzyme activity on the efficacy and safety of mirtazapine therapy in patients with depressive disorders comorbid with alcoholism. Methods: The study was conducted on 109 Russian patients with a depressive disorder, comorbid with alcohol dependence. For the correction of depressive disorders within the framework of cyclothymia, mirtazapine was prescribed to patients at a dosage of 15−45 mg/day. CYP2D6*4 genotyping (1846G> A, rs3892097) was carried out using Real-time polymerase chain reaction with allele-specific hybridization. Efficacy and safety were assessed using validated psychometric scales and an assessment of the severity of adverse drug reactions. Results: By the 9th day of the study, the severity of depressive symptoms on the HAMD scale was significantly different in patients with different genotypes: (GG) 7.0 [6.0; 8.0], (GA) 4.0 [3.8; 5.0] (p<0.001), safety indicator, estimated on a UKU scale: (GG) 3.0 [3.0; 3.0], (GA) 4.0 [4.0; 5.0] (p<0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [0.8; 3.2] (p<0.001), safety indicator, estimated on a UKU scale: (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p<0.001). Conclusion: In this study, the effect of CYP2D6 gene polymorphism on the efficacy and safety of therapy with mirtazapine was demonstrated. Carrying a minor allele A is associated with an increased risk of adverse drug reactions, but improving performance profile performance.


Mikhail S. Zastrozhin

Moscow Research and Practical Centre for Narcology of the Department of Public Health; Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: mszastrozhin@gmail.com
ORCID iD: 0000-0003-0607-4812

Russian Federation

MD, PhD.

37/1 Lyublinskaya street, 109390 Moscow; tel.: +7 (495) 709-64-04.

SPIN-код: 5681-4767

Valery V. Smirnov

National Research Center-Institute of Immunology Federal Medical-Biological Agency of Russia; I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: vvsmirnov@gmal.com
ORCID iD: 0000-0002-8232-6682

Russian Federation

PhD.

Moscow.

SPIN-код: 4171-3871

Alexander S. Sorokin

Moscow Research and Practical Centre for Narcology of the Department of Public Health

Email: assorokin@gmal.com
ORCID iD: 0000-0002-0053-8252

Russian Federation

Moscow.

SPIN-код: 5874-3924

Elena A. Grishina

Russian Medical Academy of Continuous Professional Education

Email: eagrishina@gmail.com
ORCID iD: 0000-0002-5621-8266

Russian Federation

PhD.

Moscow.

SPIN-код: 3357-3591

Kristina A. Ryzhikova

Russian Medical Academy of Continuous Professional Education

Email: karyzhikova@gmail.com
ORCID iD: 0000-0003-3505-8520

Russian Federation

Moscow.

SPIN-код: 2604-1922

Valery V. Shipitsyn

Moscow Research and Practical Centre for Narcology of the Department of Public Health

Email: vvshiptsyn@gmail.com

Russian Federation

MD.

Moscow.

SPIN-код: 2261-1516

Ludmila M. Savchenko

Russian Medical Academy of Continuous Professional Education

Email: lmsavchenko@gmai.com
ORCID iD: 0000-0002-2411-3494

Russian Federation

MD, PhD, Professor.

Moscow.

SPIN-код: 6638-6651

Oleg Z. Buzik

Moscow Research and Practical Centre for Narcology of the Department of Public Health; Russian Medical Academy of Continuous Professional Education

Email: ozhbuzik@gmail.com

Russian Federation

MD, PhD, assistant professor.

37/1 Lyublinskaya street, 109390 Moscow.

SPIN-код: 2747-6209

Sergey S. Koporov

Moscow Research and Practical Centre for Narcology of the Department of Public Health

Email: sgkoporov@gmail.com

Russian Federation

MD, PhD.

Moscow.

SPIN-код: 2747-6209

Evgeny A. Bryun

Moscow Research and Practical Centre for Narcology of the Department of Public Health; Russian Medical Academy of Continuous Professional Education

Email: eabryn@gmail.com
ORCID iD: 0000-0002-8366-9732

Russian Federation

MD, PhD, Professor.

37/1 Lyublinskaya street, 109390 Moscow.

SPIN-код: 6736-7656

Dmitry A. Sychev

Russian Medical Academy of Continuous Professional Education

Email: dasychev@gmai.com
ORCID iD: 0000-0002-4496-3680

Russian Federation

MD, PhD, Professor.

Moscow.

SPIN-код: 4525-7556

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