Serotonin Transporter Gene Polymorphism Associated with Short-Term Treatment Response to Venlafaxine

Abstract

Background: Polymorphisms of serotonin transporter, especially serotonin transporter linked promoter region (5- HTTLPR) and serotonin transporter intron 2 variable number tandem repeat (5-HTTVNTR), have been suggested to be associated with treatment response to selective serotonin reuptake inhibitors. However, there have been only few reports of the association between 5-HTTLPR or 5-HTTVNTR and treatment response to venlafaxine. Methods: 84 Korean major depressive disorder patients were included in this study. They were administered 75 mg of venlafaxine XR (extended release) for 1 week and then took 150 mg for the next 3 weeks. All patients were evaluated at baseline and week 4 by the Hamilton Depression Rating Scale (HAM-D), Montgomery-Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), and Beck Anxiety Inventory (BAI). Results: (1) Treatment response of depressive symptoms (BDI, HAM-D, MADRS) to venlafaxine at week 4 was associated with the non-s/s (l/l and l/s) genotype of 5-HTTLPR; (2) in repeated measures ANOVA, the BDI, MADRS and HAM-A scores decreased more significantly in patients with the non-s/s genotype than in those with the s/s genotype, and (3) multiple regression analyses suggested that the 5-HTTLPR polymorphism is a predictive factor for short-term treatment response to venlafaxine. However, 5-HTTVNTR showed no significant association with treatment response to venlafaxine. Both 5-HTTLPR and 5-HTTVNTR were not associated with side effects of venlafaxine. Conclusion: The 5-HTTLPR non-s/s genotype can be associated with venlafaxine treatment responses. However, further large-scale studies are warranted to confirm this finding.

A Prospective Study of Serotonin and Norepinephrine Transporter Genes and the Response to Desvenlafaxine Over 8 Weeks in Major Depressive Disorder

“…However this was in contrast to the finding by Proft et al [4], which showed a significant association between SLC6A4 genotype (l A l A ) and poor response to venlafaxine. Our results are however in alignment with another prospective study [11] involving 84 Korean MDD patients given a titrated daily dose of 75-150 mg of venlafaxineXR for 4 weeks. That study revealed that 5-HTTLPR L/L and L/S genotype patients had MADRS and HAM-A score reductions significantly greater than those patients with an S/S genotype.…”

Pharmacogenetics of antidepressant drugs: An update after almost 20 years of research

“…Meta‐analytic results further suggested an opposite effect of the variant in Caucasians versus Asians, but results remained contradictory with evidence of high heterogeneity among studies [Kato and Serretti, ]. Similarly, no association was found between STin2 and antidepressant induced side effects [Takahashi et al, ; Popp et al, ; Smits et al, ; Higuchi et al, ; Wilkie et al, ; Lee et al, ] (Supplementary Table I), and a meta‐analysis confirmed the result [Kato and Serretti, ].…”

“…Available studies mainly suggested the S allele as risk factor [Perlis et al, ; Murphy et al, ; Popp et al, ; Hu et al, ; Smits et al, ; Maron et al, ], while only one study found an opposite result for sexual dysfunction in females taking oral contraceptives [Bishop et al, ]. On the other hand, studies reporting no association between 5‐HTTLPR and antidepressant side effects were mainly performed in non‐Caucasian samples [Takahashi et al, ; Ng et al, ; Hougardy et al, ; Higuchi et al, ; Lee et al, ; Strohmaier et al, ], further suggesting a population‐specific effect of the polymorphism (Supplementary Table I). Some recent findings made the picture even more complex: (i) rs25531 may lay within the 5‐HTTLPR sequence and influence the functional effect of 5‐HTTLPR itself [Hu et al, ]; and (ii) novel even if rare 5‐HTTLPR alleles were identified (17, 18. and 11 repeats) [Ehli et al, ].…”

SLC6A2 and SLC6A4 Variants interact with Venlafaxine Serum Concentrations to Influence Therapy Outcome

“…These inconsistent results from the only 2 available studies controlling for serum levels on the other hand are in line with the ambiguous picture provided by the numerous studies not controlling for serum levels. Studies showing a better response to antidepressants in patients with the l-allele [14][15][16][29][30][31] are balanced by studies showing no effect of the genotype [26,[32][33][34] or a worse response in patients with the l-allele [35,36]. However, as it is the case in our study and the study by Dreimüller et al in all these studies different antidepressants, time points, outcome parameters and genotype definitions were used rendering a comparison nearly impossible.…”