title: Antidepressants and platinum drugs.
abstract: OBJECTIVE
  Antidepressants are frequently prescribed concurrently with anti-cancer drugs and may have synergistic, additive or antagonistic effects. The present work investigated the effect of antidepressants on the cytotoxicity of platinum agents cisplatin, carboplatin and oxaliplatin.
  
  
  METHODS
  The cytotoxicity of platinum drugs alone or in combination with antidepressants was measured in HCT116 wild-type (wt), HCT116 (p53 -/-), HT-29, SKOV3 and A2780 cells using an apoptosis-based assay.
  
  
  RESULTS
  The effect of antidepressants on platinum cytotoxicity is both cell type- and drug dependent. Mostly additive effects were observed. Desipramine and fluoxetine caused the greatest effects, with cisplatin in general being most sensitive to their presence. There is little effect of p53 status on the drug-drug interaction while the calmodulin inhibitor W7 augmented cisplatin cytotoxicity relative to carboplatin and oxaliplatin.
  
  
  CONCLUSIONS
  The drug-drug interaction between antidepressants and platinum anti-cancer agents requires detailed evaluation for optimization of patient care.
authors.affiliation: Department of Chemistry, 1001 W. Main St., Richmond VA 23284, U.S.A. npfarrell@vcu.edu.
authors.forename: Brigitte J
authors.initials: BJ
authors.lastname: Engelmann
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Farrell
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D000077150:Oxaliplatin; D014407:Tumor Cells, Cultured
chemical_list: D000928:Antidepressive Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016190:Carboplatin; D002945:Cisplatin
keywords: Antidepressants; cancer; chemotherapy; platinum