Antidepressants and ABCB1 gene C3435T functional polymorphism: a naturalistic study.
BACKGROUND
Pharmacogenetic factors may explain some of the interindividual variability of response to antidepressants in depressed patients. We focused on P-glycoprotein (P-GP), whose expression depends on a functional polymorphism of the ABCB1 gene (C3435T variants: dbSNP: rs1045642), the 3435CC genotype being linked to a high level of P-GP expression. Acting as an efflux pump at the blood-brain barrier, P-GP reduces the intracellular penetration of many drugs. Little is known about the interaction between P-GP and response to antidepressants. The objective of this study is to assess whether the response to antidepressants in depression differs in patients with the 3435CC genotype as compared to patients with the 3435CT and 3435TT genotypes.


METHODS
117 in-patients with a major depressive episode requiring a new antidepressant treatment were enrolled in this prospective naturalistic 4-week study. Response to antidepressants was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, the Clinician Global Impression Improvement and Therapeutic Index, and weight change. ABCB1 genotyping was performed using the Taqman method. Clinical assessment was performed blind from genotypes.


RESULTS
We failed to show any significant effect of the ABCB1 polymorphism in position 3435 on antidepressant efficacy or tolerance.


CONCLUSIONS
While some in vitro studies showed an influence of P-GP on cerebral concentrations of antidepressants, our results do not support the hypothesis that the C3435T polymorphism is involved in therapeutic response and safety of antidepressants in naturalistic clinical conditions, confirming results of previous studies on efficacy. Nonetheless, some methodological limitations may explain our negative results.
Menu
Patrick
P
INSERM U669, Department of Psychiatry, Bicêtre University Hospital, Le Kremlin-Bicêtre, France. patrickmenu @ hotmail.com
Gressier
Florence
F
Verstuyft
Céline
C
Hardy
Patrick
P
Becquemont
Laurent
L
Corruble
Emmanuelle
E
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000928:Antidepressive Agents