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.

Use of SSRI, But Not SNRI, Increased Upper and Lower Gastrointestinal Bleeding

Selective serotonin receptor inhibitors (SSRIs) are usually used as the first line medications to treat depression and other psychogenic disorders. The main concerns of using SSRIs is the increased risk of internal bleeding including gastrointestinal, genitourinary, and intracranial bleeding. This article is about the nationwide study that was done in Taiwan to discover whether SSRI or serotonin- noradrenaline reuptake inhibitors (SNRIs) usage causes increased risk of internal bleeding.

The subjects were randomly picked from Taiwan National Health Insurance Research Database.  The study group consists of 8809 SSRI users and 944 SNRI users. Patients with alcohol related disease, inflammatory bowel disease, bleeding of GI tract before January 1, 2000 were excluded from the study. The control group consists of 39,012 subjects who had not taken SSRI or SNRI. Both groups were followed from 2000 to 2010.

The results showed that the SSRI group users had a much higher incidence of upper gastrointestinal bleeding (UGIB) and lower gastrointestinal bleeding (LGIB) than the control group. The results also showed that SSRI are more likely to cause LGIB than UGIB. The possible reason behind this is that SSRI decreases serotonin availability which is an important factor in platelet aggregation. SSRIs also increases gastric acid secretion and aggravation of NSAID-induced gastric mucosal injury. The study also noticed that male are more likely to experience UGIB and LGIB than female.

This study is very interesting to me. SSRIs and SNRIs are relatively new classes of medications so this study shows that researchers are still trying to find out possible side effects of these medications. Now that there is strong evidence that there is a strong link between SSRIs and GI bleeding, I am interested in whether SSRIs will still continue to be the first line medications used to treat depression and other psychogenic disorders. I am also interested in other differences between SSRIs and SNRIs.


Cheng Yuan-Lung, Hu Hsiao-Yun, Lin Xi-Hsuan, Luo Jiing-Chyuan, Peng Yen-Ling, Hou Ming-Chih, Lin Han0chien,Lee Fa-Yauh. Use of SSRI, But Not SNRI, Increased Upper and Lower Gastrointestinal Bleeding: A Nationwide Population-Based Cohort Study in Taiwan. Medicine.10.1097/MD.0000000000002022. (published 20 November 2015).