In:
European Psychiatry, Cambridge University Press (CUP), Vol. 41, No. S1 ( 2017-04), p. s238-s238
Abstract:
Antidepressants are the first-line treatment of major depressive disorder, but response rates following the first antidepressant medication are moderate. Objectives Clinical efficacy requires to overcome the blood-brain barrier where p-gp molecules are located. If they recognize and bind an antidepressant, they pump it back into the circulation. If the antidepressant is not recognized, the passage is not impaired by p-glycoproteins. Aims We studied whether variants in the ABCB1 gene that encodes the p-glycoprotein have an effect on blood-brain passage of antidepressants and as consequence on their clinical benefit. Methods ABCB1 gene variants were determined with sequencing (Illumina Bead), substrate property analysis employed mice with deletion of ABCB1-analog genes. Clinical protocols followed those of the MARS-project. Results – The SNPs rs2032583 and rs2235015 provide the best clinical information about blood-brain-penetrance, with CC/CT and TT/GT being the favourable gene variants whereas TT and GG are less favourable. This distinction holds only true if antidepressants are p-glycoprotein substrates; – in the presence of the favourable gene-variant patients treated with an antidepressant that is a p-glycoprotein substrate are more likely to remit in shorter time; – in the presence of the less favourable gene-variant treatment with a substrate, higher dosages and augmentation strategies, or switch to non-substrates are recommended. Conclusion From these data, a treatment algorithm was developed that maximizes treatment benefit and minimizes adverse effects. Disclosure of interest The authors have not supplied their declaration of competing interest.
Type of Medium:
Online Resource
ISSN:
0924-9338
,
1778-3585
DOI:
10.1016/j.eurpsy.2017.02.002
Language:
English
Publisher:
Cambridge University Press (CUP)
Publication Date:
2017
detail.hit.zdb_id:
2005377-0
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