Effects of CYP2D64 polymorphism on the steady-state concentration of paroxetine in patients diagnosed with depressive episode and comorbid alcohol use disorder

Introduction: Selective serotonin reuptake inhibitors have a common and increasing use for the treatment of patients diagnosed with depressive disorders. Some of them do not respond adequately to therapy, and numerous previous studies have indicated an increased risk of type A adverse drug reactions...

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Published in:Journal of psychopharmacology (Oxford) 2022-10, Vol.36 (10), p.1146-1150
Main Authors: Zastrozhin, Mikhail, Skryabin, Valentin, Petukhov, Aleksey, Pankratenko, Elena, Pozdniakov, Sergei, Ivanchenko, Valentina, Horyaev, Denis, Vlasovskih, Roman, Bryun, Evgeny, Sychev, Dmitry
Format: Article
Language:English
Subjects:
Adult
Alcohol use
Alcoholism - drug therapy
Antidepressants
Comorbidity
CYP2D6 protein
Cytochrome P-450 CYP2D6 - genetics
Cytochrome P450
Drug dosages
Gene polymorphism
Genotyping
High-performance liquid chromatography
Humans
Mass spectroscopy
Mental disorders
Middle Aged
Paroxetine
Paroxetine - pharmacokinetics
Patients
Polymorphism
Polymorphism, Genetic
Selective Serotonin Reuptake Inhibitors - pharmacokinetics
Serotonin uptake inhibitors
Statistical analysis
Tandem Mass Spectrometry
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Summary:Introduction: Selective serotonin reuptake inhibitors have a common and increasing use for the treatment of patients diagnosed with depressive disorders. Some of them do not respond adequately to therapy, and numerous previous studies have indicated an increased risk of type A adverse drug reactions. Objective: The objective of our study was to evaluate the effect of 1846G>A polymorphism of CYP2D6 on the concentration/dose ratio of paroxetine. Material and methods: The study enrolled 267 patients with depressive episode (average age, 40.3 ± 14.3 years). Therapy included paroxetine in an average daily dose of 25.1 ± 9.5 mg per day. The efficacy and safety rates of treatment were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Therapeutic drug monitoring has been performed using high-performance liquid chromatography mass spectrometry (HPLC-MS/MS). Results: Our study revealed the statistically significant results in terms of treatment efficacy (Hamilton Depression Rating Scale scores): (GG) 2.0 [1.0; 3.0] and (GA) 4.0 [2.0; 5.0], p 
ISSN:0269-8811
1461-7285
DOI:10.1177/02698811221112939