An article that will soon appear in the American Journal of Psychiatry suggests that it may be possible to predict who will respond to different antidepressants using a genetic test. The study looked at whether by testing for specific genetic variants of a protein involved in transporting drugs and other potentially toxic substances into and out of cells and across the blood brain barrier (a P-glycoprotein called ABCB1) one could identify who would respond best to a given antidepressant.
The ABCB1 protein is one of a set of active transport proteins located in the cell membrane the transport molecules into and out of the cell. These molecules may play a critical role in determining the levels of medications present in cells of various kinds and therefore the likelihood of a response to those medications.
With newer antidepressants (such as the serotonin reuptake inhibitors) blood levels are not predictive of response. This is probably because what affects the level of the medication in brain cells is not how well it’s absorbed into the blood but whether or not it stays in the brain. In other words how it is transported into and out of the brain across the blood brain barrier. And the P-glycoproteins perform that function.
Earlier studies on this subject were intriguing. Several ABCB1 single-nucleotide polymorphisms (variants) were found to be predictors of antidepressant efficacy or side effects in some but not all of the studies.
This study looked at 10 variants of ABCB1 and treatment response in a very large sample of 683 patients with major depressive disorder who were randomly assigned to treatment with escitalopram, sertraline or venlafaxine. As you can see in the graph to the right, response to treatment with either a pure serotonin reuptake inhibitor (escitalopram or sertraline) or a serotonin norepinephrine reuptake inhibitor (venlafaxine) vary depending on the nature of the ABCB1 gene.
40 to 45% of people with the G/G variant achieved remission of depression with a serotonin reuptake inhibitor (escitalopram or sertraline), whereas only 20% achieved remission with venlafaxine. By contrast, with the T/T variant 35% achieved remission with venlafaxine compared with 15 to 20% with the serotonin reuptake inhibitor.
The importance of the T/T variant predicting remission with venlafaxine was even greater in those with cognitive impairment. In other words, those people with cognitive impairment who had the T/T variant were much less likely to respond to a pure serotonin reuptake inhibitor and much more likely to respond to venlafaxine.
This result, combined with other studies, suggest that genetic tests may be even more important in predicting treatment response in older patients.
Note, although this finding is certainly tantalizing, we were unable to locate a company that is currently doing commercial ABCB1 genotyping. We will keep you posted if we find out more on this topic. Meanwhile if you’re interested in the overall topic of predicting treatment response to antidepressants you may want to read more about the iSPOT-D collaborative trial which has already published a number of tantalizing articles on the subject.
“ABCB1 Genetic Effects on Antidepressant Outcomes: A Report From the iSPOT-D Trial.” Alan F. Schatzberg, M.D.; Charles DeBattista, M.D.; Laura C. Lazzeroni, Ph.D.; Amit Etkin, M.D., Ph.D.;Greer M. Murphy, Jr., M.D., Ph.D.; Leanne M. Williams, Ph.D. American Journal of Psychiatry. epublication ahead of print. January 2015.