Polymorphisms in the drug transporter gene ABCB1 in treatment resistant depression: clinical practice

Polymorphisms in the drug transporter gene ABCB1 account for differences in the clinical efficiency of antidepressants, most likely by influencing their access to the brain. The abcb1a and abcb1b genes are two homologues in mice, whereas P-glycoprotein (P-gp) is encoded by a single gene in humans (ABCB1). Although abcb1a and abcb1b are not always expressed in the same organs, their overall distribution in the mouse tissue is very similar to that of the single ABCB1 gene in humans, indicating that abcb1a together with abcb1b function in the same manner in the mouse as the single gene ABCB1 does in humans. P-gp at the blood-brain barrier acts as an active efflux pump for a wide range of compounds, including several antidepressants. It has been shown that some antidepressants are substrates of P-gp in mice after both single dose and repeated administration of an antidepressant. The aim of this presentation is to show two possible approaches of pharmacological therapies for treatment resistant depression, after determing the P-gp status as „T-carrier“ which is associated with low remission rates. The clinician may, in case of a T-carrier: 1) increase the dosage in order to compensate for the hyperactive drug-export out of the brain by P-gp, or 2) switch the medication to non-substrates of P-gp. P-gp genotyping may be helpful for the clinician to determine the drug's bioavailability in the brain and may even predict the response of an individual patient to a certain drug.