Combination of mirtazapine and paroxetine: possible clinically demonstrated interaction?

Cas Lek Cesk. 2019 Winter;158(7-8):310-313.


We currently have a wide range of antidepressants available. However, the mechanisms of action are different, giving a theoretical justification for their combination in the failure of monotherapy. However, the combination of drugs entails, in addition to benefits, an increase in the risk of, for example, drug interactions. Many drug interactions in psychiatry are due to the pharmacokinetic interactions between drugs, where their plasma concentrations are altered by inhibiting or inducing cytochrome P450 isoenzymes, especially CYP2D6 and CYP3A4 and P-glycoprotein. When treating depression, we should consider the risks and benefits of combination therapy in individual patients and take measures to minimize the side effects of medicines. The case report describes a case of a patient who reported significant depression after adding paroxetine and mirtazapine to psychiatric medication. As a theoretical cause, it discusses the possible clinically demonstrated interaction between paroxetine and mirtazapine, which has been clinically manifested by fatigue and pronounced daytime sleepiness.

Keywords: P450; SSRI; antidepressants; cytochrome; depression; mirtazapine; pharmacokinetics interactions.

Publication types

  • Case Reports

MeSH terms

  • Antidepressive Agents* / administration & dosage
  • Antidepressive Agents* / adverse effects
  • Cytochrome P-450 Enzyme System
  • Depression* / chemically induced
  • Drug Interactions*
  • Humans
  • Mirtazapine* / administration & dosage
  • Mirtazapine* / adverse effects
  • Paroxetine* / administration & dosage
  • Paroxetine* / adverse effects


  • Antidepressive Agents
  • Paroxetine
  • Cytochrome P-450 Enzyme System
  • Mirtazapine