Polymorphism Associated with the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depression

Are pharmacogenetics-based strategies the key to effective depression treatment? This study set out to dig deeper into this questions by researching additional polymorphisms affecting the efficacy of SSRIs. Previously, a polymorphism in the serotonin transporter linked promoter region was found to be associated with a difference in SSRI efficacy. This polymorphism, however, only explained a small amount of the differences in efficacy seen in the treatment of those with depression. So this study intended to find additional polymorphisms in the gene coding for the serotonin transporter (SLC6A4) accounting for different responses in SSRI/SNRI treatment. (Remember that the serotonin transporter is the target of serotonin uptake inhibitors)

A 6-week randomized controlled trial of 201 patients with major depressive disorder was performed. Subjects were given paroxetine 20-40 mg/d (SSRI), fluvoxamine 50-150 mg/d (SSRI), or milnacipran 50-75 mg/d (SNRI). Efficacy of the therapy was measured by comparing baseline Hamilton Depression Rating Scale (HAM-D) values with those from the end of the 6 week treatment period. Genomic DNA was gathered from each patient and sequenced so that SLC6A4 mutations could be analyzed. 32 variants were found, and 17 of these were new polymorphisms. One of the polymorphisms, rs3813034, resulted in significantly altered HAM-D scores for each medication administered, suggesting it has an effect on SSRI/SNRI response.

Considering all the treatment hurdles those with depression face (medications take a lot of time for effects to be realized and they may not be effective for many people), I think it is important to research the pharmacogenetics involved with SSRIs. This can help create more individualized treatments for patients who do not have months to spend time putting their well-being on hold while they try numerous antidepressants before finding one that works. Do you think it would be practical and possible to someday have a genotype-based protocol for antidepressant treatments?

Nonen, S et al. Polymorphism of rs3813034 in Serotonin Transporter Gene SLC6A4 Is Associated With the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depressive Disorder: Sequencing Analysis of SLC6A4. J. Clin. Psychopharmacol. 2016; 36(1):27-3.