Serotonin transporter gene (5-HTTLPR) polymorphism and efficacy of selective serotonin reuptake inhibitors--do we have sufficient evidence for clinical practice

Abstract

Depression pharmacotherapy can be described with weak predictability of individual response. Antidepressants are prescribed based on trial and error, as it is not possible to determine which patients will respond to antidepressants. It would appear that pharmacogenetics is the most promising path towards achieving the goal of individualized therapy. Today, the most commonly prescribed antidepressants are those from the group of selective serotonin reuptake inhibitors (SSRI). The most investigated genetic variations in the prediction and individualization of antidepressant therapy is the serotonin transporter gene (5-HTTLPR). The objective of this paper is to provide an overview of the research to date on 5-HTTLPR polymorphism in response to SSRI. This paper gives an overview of 35 studies investigating the efficacy of SSRI antidepressants in dependence of 5-HTTLPR polymorphism. The results of three meta-analyses examining this issue are discussed. Briefly, the great majority of studies conducted have shown that L-allele carriers have a faster and better response to SSRI antidepressants, if they are Caucasians. Studies with negative results included ethnically mixed populations, and it is known that there are different allele frequencies among ethnic groups and the consequence of this are the varying results of pharmacogenetic studies. Pharmacogenetic analysis of 5-HTTLPR polymorphism has proven to be economically cost-effective considering the recurrent course of the disease. It would appear that the response to SSRI antidepressants and the development of adverse reactions are associated with 5-HTTLPR polymorphism in Caucasians and this pharmacogenetic analysis could be one of the first in future clinical practice.