Serotonin transporter polymorphism and response to SSRIs in major depression and relevance to anxiety disorders and substance abuse

Pharmacogenomics. 2000 Aug;1(3):335-41. doi: 10.1517/14622416.1.3.335.


The selective serotonin re-uptake inhibitors (SSRIs) which modulate serotonergic activity are effective in the treatment of serotonin-related mental disorders, such as depression and anxiety. These agents bind to the serotonin transporter (5-HTT) and inhibit its capacity to transport serotonin (5-hydroxytryptamine; 5-HT). A functional polymorphism in the promoter region of 5-HTT (5-HTTLPR) has been described. The insertion variant of this polymorphism (long allele) is associated with higher expression of brain 5-HTT compared to the deletion variant (short allele). An association between the 5-HTTLPR polymorphism and mental disorders has been reported by some, but not all, investigators. In addition, the 5-HTT gene polymorphisms were found to be associated with a better and faster response to SSRIs with or without pindolol augmentation in depressed patients. Further studies are needed to clarify the relationship between the 5-HTT genotype, the susceptibility to mental disorders, the response to serotonergic agents and the side effect profile.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / genetics*
  • Carrier Proteins / genetics*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / genetics*
  • Humans
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Pharmacogenetics
  • Polymorphism, Genetic / genetics*
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Substance-Related Disorders / drug therapy*
  • Substance-Related Disorders / genetics*


  • Antidepressive Agents
  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors