Evaluation of cytogenetic and DNA damage induced by the antidepressant drug-active ingredients, trazodone and milnacipran, in vitro

Drug Chem Toxicol. 2017 Jan;40(1):57-66. doi: 10.1080/01480545.2016.1174870. Epub 2016 May 4.


Trazodone and milnacipran are the active antidepressant drugs that are being used in the treatment of psychiatric disorders. In this study, the in vitro genotoxic effects of trazodone and milnacipran have been determined in human peripheral blood lymphocytes by using chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN), and comet assays. 3.13; 6.25; 12.50; 25.00; 50.00; and 75.00 μg/mL concentrations of trazodone and 2.50; 5.00; 10.00; 20.00; 30.00; and 40.00 μg/mL concentrations of milnacipran were used. Trazodone and milnacipran significantly increased the frequency of CAs and SCEs compared with the control. Both of the active ingredients raised the MN frequency in a dose-dependent manner. Mitotic index was significantly decreased, but replication and nuclear division indices were not affected at all treatments. Trazodone was statistically increased the mean comet tail intensity, tail length, and tail moment at three concentrations (6.25; 12.50; and 25.00 μg/mL) compared with control. Two highest concentrations (50 and 75 μg/mL) of trazodone were toxic in the comet assay. Milnacipran increased the comet tail intensity, tail length, and tail moment at all concentrations. It is concluded that trazodone and milnacipran have clastogenic, mutagenic, and cytotoxic effects on human lymphocytes in vitro.

Keywords: DNA damage; Trazodone; genotoxicity; human lymphocytes; milnacipran.

MeSH terms

  • Adult
  • Antidepressive Agents / toxicity*
  • Cells, Cultured
  • Chromosome Aberrations / chemically induced*
  • Comet Assay
  • Cyclopropanes / toxicity*
  • DNA Damage*
  • Dose-Response Relationship, Drug
  • Female
  • Healthy Volunteers
  • Humans
  • Lymphocytes / drug effects
  • Lymphocytes / pathology
  • Male
  • Micronuclei, Chromosome-Defective / chemically induced
  • Milnacipran
  • Mutagenicity Tests / methods
  • Sister Chromatid Exchange / drug effects*
  • Sister Chromatid Exchange / genetics
  • Trazodone / toxicity*
  • Young Adult


  • Antidepressive Agents
  • Cyclopropanes
  • Milnacipran
  • Trazodone