A candidate gene study of serotonergic pathway genes and pain relief during treatment with escitalopram in patients with neuropathic pain shows significant association to serotonin receptor2C (HTR2C)

  • Charlotte Brasch-Andersen
  • Malik U. Møller
  • Lene Christiansen
  • Mikael Thinggaard
  • Marit Otto
  • Kim Brøsen
  • Søren H. Sindrup



Previous studies have shown that a small fraction of patients with peripheral neuropathic pain experiences >50% pain relief during treatment with selective serotonin reuptake inhibitors (SSRIs), whereas most patients have no or only slight relief. The aim of this study was to investigate the association between polymorphisms in genes involved in the serotonergic pathway and the effect of escitalopram on peripheral neuropathic pain.


We genotyped 34 participants from a placebo-controlled trial of escitalopram in peripheral neuropathic pain for polymorphisms in five genes: the serotonin receptor 2A (HTR2A) gene, the serotonin receptor 2C (HTR2C) gene, the ABCB1 gene encoding for the P-glycoprotein, the CYP2C19 gene, and the serotonin transporter gene (SLC6A4).


The SNP rs6318 (Cys23Ser) in the HTR2C gene showed significant association with treatment response in men (p = 0.047), with 75% carrying the C allele being responders. The same tendency was seen in women. Similarly, carriership of the C allele at rs6318 was associated with better pain relief during treatment with escitalopram [odds ratio (OR) 15.5, p = 0.014)] Furthermore, there was a tendency of better relief with increasing number of short alleles for the 5-HTTLPR polymorphism of the serotonin transporter (OR 5.7, p = 0.057). None of the other polymorphisms showed a significant association with treatment response to escitalopram.


This study indicates that variation in the HTR2C gene is associated to the pain-relieving effect of escitalopram in patients with painful polyneuropathy.


Pharmacogenetics Neuropathic pain SSRI treatment Treatment response 



The authors thank research nurses M. Sørensen and R. Mitzi Henriksen for collecting blood samples, and lab technician P. Jordan for skillful technical work. We declare no conflict of interest.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Charlotte Brasch-Andersen
    • 1
    • 2
  • Malik U. Møller
    • 1
  • Lene Christiansen
    • 2
    • 3
  • Mikael Thinggaard
    • 3
  • Marit Otto
    • 4
    • 5
  • Kim Brøsen
    • 1
    • 6
  • Søren H. Sindrup
    • 4
  1. 1.Department of Clinical Biochemistry & PharmacologyOdense University HospitalOdenseDenmark
  2. 2.Department of Clinical GeneticsOdense University HospitalOdenseDenmark
  3. 3.Epidemiology, Institute of Public HealthUniversity of Southern DenmarkOdenseDenmark
  4. 4.Department of NeurologyOdense University HospitalOdenseDenmark
  5. 5.Department of NeurophysiologyAarhus University HospitalAarhusDenmark
  6. 6.Clinical Pharmacology, Institute of Public HealthUniversity of Southern DenmarkOdenseDenmark

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