Tryptophan hydroxylase gene associated with paroxetine antidepressant activity

Alessandro Serretti, Raffaella Zanardi, Cristina Cusin, David Rossini, Cristina Lorenzi, Enrico Smeraldi

Research output: Contribution to journalArticlepeer-review


The possible association of the A218C tryptophan hydroxylase (TPH) gene variant with the antidepressant activity of paroxetine was investigated in a sample of 121 inpatients affected by a major depressive episode and treated with paroxetine 20-40 mg with either placebo or pindolol in a double blind design for 4 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. TPH allelic variants were determined in each subject using a PCR-based technique. TPH*A/A and TPH*A/C variants were associated with a poorer response to paroxetine treatment when compared to TPH*C/C (P=0.005); this difference was not present in the pindolol augmented group. Other variables, such as sex, diagnosis, presence of psychotic features, severity of depressive symptomatology at baseline and paroxetine plasma level, were not associated with the outcome. TPH gene variants are therefore a possible modulator of paroxetine antidepressant activity.

Original languageEnglish
Pages (from-to)375-380
Number of pages6
JournalEuropean Neuropsychopharmacology
Issue number5
Publication statusPublished - 2001


  • Antidepressant treatment
  • Mood disorders
  • Pharmacogenetics
  • Pindolol

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Neurology
  • Pharmacology
  • Psychology(all)


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