Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment

Roy H. Perlis, David Mischoulon, Jordan W. Smoller, Yu-Jui Yvonne Wan, Stefania Lamon-Fava, Keh Ming Lin, Jerrold F. Rosenbaum, Maurizio Fava

Research output: Contribution to journalArticlepeer-review

165 Scopus citations


Background: The short (S) allele of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been associated with poorer antidepressant response in major depressive disorder (MDD) and with antidepressant-induced mania. This study investigated a possible association with treatment-emergent insomnia or agitation. Methods: Thirty-six outpatients with MDD were genotyped at 5HTTLPR and treated with open-label fluoxetine up to 60 mg/day. Treatment-emergent adverse effects were assessed at each study visit. Results: Of nine subjects homozygous for the "S" allele, seven (78%) developed new or worsening insomnia, versus 6 of 27 (22%) non-"S"-homozygous subjects (Fisher's exact p = .005). Similarly, six of nine subjects homozygous for the "S" allele (67%) developed agitation, versus 2 of 27 (7%) of non-"S"-homozygous subjects (Fisher's exact p = .001). Conclusions: The "S" allele of the 5HTTLPR may identify patients at risk for developing insomnia or agitation with fluoxetine treatment. This preliminary result requires confirmation in larger samples.

Original languageEnglish (US)
Pages (from-to)879-883
Number of pages5
JournalBiological Psychiatry
Issue number9
StatePublished - Nov 1 2003


  • Adverse event
  • Agitation
  • Depression
  • Fluoxetine
  • Insomnia
  • Serotonin transporter

ASJC Scopus subject areas

  • Biological Psychiatry


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