The serotonin transporter promoter polymorphism (5-HTTLPR) affects the relation between antidepressant serum concentrations and effectiveness in major depression

Pharmacopsychiatry. 2012 May;45(3):108-13. doi: 10.1055/s-0031-1291347. Epub 2011 Nov 15.

Abstract

Introduction: Both the serotonin transporter promotor polymorphism (5-HTTLPR) and serum concentrations of SSRIs have been shown to affect response to SSRIs. Results, however, are inconsistent. The aim of this study was to investigate whether remission or response to SSRIs is influenced by an interaction of 5-HTTLPR and SSRI serum concentrations.

Methods: 49 patients with major depression and SSRI treatment were genotyped for the 5-HTTLPR locus including the rs25531. Drug serum concentrations and depression severity were measured weekly.

Results: Logistic regression analysis revealed a significant association between 5-HTTLPR, SSRI serum concentrations and response to treatment. A favourable treatment outcome correlated with SSRI serum concentration in 5-HTTLPR-L(A) allele carriers (r² = 34.3 %; p = 0.001), but not in S/L(G)-allele carriers (p = 0.31).

Discussion: In the group of L(A) allele carriers, those MDD patients with a high antidepressant serum concentrations responded better to treatment than patients with a low serum concentration. We conclude that the 5-HTTLPR might affect reponse to SRRI subject to serum concentrations. If replicated this might be a starting point for prospective clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Antidepressive Agents / blood
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / genetics*
  • Female
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Promoter Regions, Genetic / genetics
  • Selective Serotonin Reuptake Inhibitors / blood
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Young Adult

Substances

  • Antidepressive Agents
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors