Combination of intravenous S-ketamine and oral tranylcypromine in treatment-resistant depression: A report of two cases

Eur Neuropsychopharmacol. 2015 Nov;25(11):2183-4. doi: 10.1016/j.euroneuro.2015.07.021. Epub 2015 Aug 6.


Ketamine, a rapid-acting antidepressant and anti-suicidal agent, is thought to increase brain monoamine levels by enhancing monoamine release or inhibiting presynaptic monoamine-reuptake. Here we present two female inpatients suffering from treatment-resistant depression with recurrent severe suicidal crises receiving a combination of intravenous S-ketamine and oral tranylcypromine, which is a well-known irreversible monoamine oxidase (MAO) inhibitor. Since inhibition of monoamine-reuptake with concurrent blockade of MAO might trigger sympathomimetic crisis, this combination is considered hazardous. Nonetheless, cardiovascular parameters remained stable in both patients, while good anti-suicidal effects were observed. Hence, we put serious doubt on whether monoamine-reuptake inhibition is a relevant pharmacological effect of ketamine in humans.

Keywords: Irreversible monoamine oxidase inhibition; Ketamine; Monoamine-reuptake inhibition; Tranylcypromine; Treatment-resistant depression.

Publication types

  • Case Reports

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Adult
  • Aged
  • Antidepressive Agents / administration & dosage*
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Female
  • Humans
  • Inpatients
  • Ketamine / administration & dosage*
  • Monoamine Oxidase Inhibitors / administration & dosage
  • Suicide Prevention
  • Tranylcypromine / administration & dosage*


  • Antidepressive Agents
  • Monoamine Oxidase Inhibitors
  • Tranylcypromine
  • Ketamine