Open AccessThe Effect of Cyp2d6 Gene Polymorphism on the Efficacy and Safety of Mirtazapine in Patients with Depressive Disorders Comorbid with Alcohol
Author(s) -
Михаил Сергеевич Застрожин,
Застрожин Михаил Сергеевич,
В. В. Смирнов,
Смирнов Валерий Валериевич,
А. С. Сорокин,
Сорокин Александр Сергеевич,
Elena A. Grishina,
Гришина Елена Анатольевна,
К. А. Акмалова,
Рыжикова Кристина Анатольевна,
В. В. Шипицын,
Шипицын Валерий Валериевич,
Л. М. Савченко,
Савченко Людмила Михайловна,
О. Ж. Бузик,
Бузик Олег Жанович,
Sergey S. Koporov,
Копоров Сергей Георгиевич,
Evgeny А. Bryun,
Брюн Евгений Алексеевич,
Д. А. Сычев,
Сычев Дмитрий Алексеевич
Publication year - 2019
Publication title -
vestnik rossijskoj akademii medicinskih nauk
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.122
H-Index - 15
eISSN - 2414-3545
pISSN - 0869-6047
DOI - 10.15690/vramn1075
Subject(s) - mirtazapine , hamd , major depressive disorder , medicine , genotyping , adverse effect , alcohol use disorder , psychiatry , genotype , alcohol , gene , antidepressant , significant difference , biology , genetics , biochemistry , amygdala , hippocampus
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 1545 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] (p0.001), safety indicator, estimated on a UKU scale: (GG) 3.0 [3.0; 3.0], (GA) 4.0 [4.0; 5.0] (p0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [0.8; 3.2] (p0.001), safety indicator, estimated on a UKU scale: (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p0.001).
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.