1. Influence of eight ABCB1 polymorphisms on antidepressant response in a prospective cohort of treatment‐free Russian patients with moderate or severe depression: An explorative psychopharmacological study with naturalistic design
- Author
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Lisanne M Geers, Bob Wilffert, Taichi Ochi, Daniel J. Touw, Innokentiy S. Losenkov, G. G. Simutkin, Nikolay A. Bokhan, Diana Z Paderina, Svetlana A. Ivanova, Natalya M. Vyalova, Anton J. M. Loonen, Ivan V Pozhidaev, PharmacoTherapy, -Epidemiology and -Economics, Reproductive Origins of Adult Health and Disease (ROAHD), Pharmaceutical Analysis, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Medicinal Chemistry and Bioanalysis (MCB), Groningen Research Institute for Asthma and COPD (GRIAC), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
- Subjects
medicine.medical_specialty ,ABCB1 gene ,ATP Binding Cassette Transporter, Subfamily B ,Genotype ,психофармакология ,Affect (psychology) ,Polymorphism, Single Nucleotide ,P-гликопротеин, белок ,депрессии ,генетические вариации ,Internal medicine ,Humans ,Medicine ,SNP ,Pharmacology (medical) ,Prospective Studies ,Гамильтона шкала для оценки депрессии ,Prospective cohort study ,Depression (differential diagnoses) ,chemistry.chemical_classification ,Depressive Disorder, Major ,Depression ,business.industry ,ABCB1, ген ,Mental health ,Antidepressive Agents ,Psychiatry and Mental health ,Neurology ,chemistry ,Antidepressant ,Neurology (clinical) ,business ,Tricyclic - Abstract
Background Many antidepressants are substrates of P-glycoprotein, an efflux transporter in the blood-brain-barrier encoded by the ABCB1 gene. Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response. Method 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton-Depression-Rating-Scale (HAMD-17)-scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene-polymorphisms and reduction in HAMD-17 score were assessed using independent t-test and multiple linear regression. Results Tricyclic antidepressants were associated with a higher reduction of HAMD-17 score when compared to SSRIs. The SNP rs2235040 A-allele had a significant positive influence on the Delta HAMD-17((0 -> 2W)) score but a significant negative influence on the Delta HAMD-17((2 -> 4W)) score. The rs4148739 G-allele had a significant negative influence on the Delta HAMD-17((0 -> 2W)) score but a significant positive influence on the Delta HAMD-17((2 -> 4W)) score. The SNP rs2235015 T-allele is significant negatively related to the Delta HAMD-17((2 -> 4W)) score. Conclusion ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.
- Published
- 2021