Original scientific paper

https://doi.org/10.24869/psyd.2018.157

THE COMBINED EFFECT OF CYP2D6 AND DRD2 Taq1A POLYMORPHISMS ON THE ANTIPSYCHOTICS DAILY DOSES AND HOSPITAL STAY DURATION IN SCHIZOPHRENIA INPATIENTS (OBSERVATIONAL NATURALISTIC STUDY)

Alexey A. Kurylev orcid.org/0000-0003-3031-4572 ; Department of clinical pharmacology, P.P. Kaschenko 1st City Mental Hospital, Saint-Petersburg, Russia; Department of Clinical pharmacology and evidence-based medicine, First Saint-Petersburg state medical university n.a. I.P. Pavlov, Saint-Petersburg, Ru
Vadim M. Brodyansky ; Laboratory of Molecular Genetics, Serbsky National Medical Research Center on Psychiatry and Addictions, Moscow, Russia
Boris V. Andreev orcid.org/0000-0001-5982-5523 ; Department of clinical pharmacology, P.P. Kaschenko 1st City Mental Hospital, Saint-Petersburg, Russia; Depatment of pharmacology, Saint-Petersburg state university, Saint-Petersburg, Russia
Alexander O. Kibitov ; Laboratory of Molecular Genetics, Serbsky National Medical Research Center on Psychiatry and Addictions, Moscow, Russia
Oleg V. Limankin ; Department of clinical pharmacology, P.P. Kaschenko 1st City Mental Hospital, Saint-Petersburg, Russia
Sergey N. Mosolov orcid.org/0000-0002-5749-3964 ; Department of Mental Disorders Therapy, Serbsky National Medical Research Center on Psychiatry and Addictions, Moscow, Russia

Abstract

Background: To assess the correlation between the antipsychotics (AP) mean daily doses, hospital stay duration and CYP2D6,
DRD2 polymorphisms in naturalistic study.
Subjects and methods: CYP2D6 polymorphisms *3, *4, *5, *6, *1XN and DRD2/ANKK1 Taq1A polymorphisms were genotyped
in a cohort of 226 Caucasian schizophrenic inpatients. AP daily doses, hospital stay duration and AP treatment duration were taken
from medical records. To compare mean daily doses of AP among CYP2D6 PMs, EMs, UMs and DRD2/ANKK1 Taq1A carriers the
actual AP doses were converted to chlorpromazine (CPZ) equivalents and DDD (defined daily dose).
Results: Significant correlation (p=0.004) between CYP2D6 metabolic activity and AP mean daily doses was observed only
among DRD2/ANKK1 Taq1A polymorphic allele carriers: 250.53 (95%CI: 154.90-346.17), 473.82 (95%CI: 426.99-520.64) 602.77
(95%CI: 469.65-735.88) CPZ equivalents in PMs, EMs and UMs, consequently. PMs with DRD2/ANKK1 Taq1A CT genotype
received significantly lower doses of AP comparing to CC genotype (p=0.02). Mean hospital stay duration of PMs+UMs was
significantly higher comparing to EMs (66.4 days (95% CI: 56.9-75.8) vs 50.2 days (95%CI: 45.5-54.7); p=0.047).
Conclusions: In a cohort of schizophrenia inpatients CYP2D6 metabolic activity affects mean AP daily dose only in the presence
of DRD2 Taq1A polymorphic allele. CYP2D6 metabolic activity correlates independently from DRD2 Taq1A polymorphism with
hospital stay duration. Subpopulation of schizophrenia inpatients with altered CYP2D6 activity (PMs and UMs) carriers of Taq1A
polymorphisms needs special attention of clinicians in aligning of AP treatment.

Keywords

CYP2D6; DRD2; schizophrenia; antipsychotics; pharmacogenetics; polymorphism

Hrčak ID:

202062

URI

https://hrcak.srce.hr/202062

Publication date:

26.6.2018.

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