Antidepressants: clinically relevant drug interactions to be considered

Pharmacology. 2010;86(4):203-15. doi: 10.1159/000319744. Epub 2010 Sep 8.


Drug interactions in clinical practice are common and have developed into an increasing challenge for the medical profession. Specifically antidepressant drugs (ADs), which are among the 5 most frequently prescribed drugs, are predestined for adverse drug interactions because of their multiple mechanisms of action and/or their influence on drug-metabolizing cytochrome P450 (CYP) enzymes. Although selective serotonin reuptake inhibitors (SSRIs) and other new-generation ADs have an overall improved safety profile, their potential for drug interactions is to be considered. A review of the current literature has been performed, and selected examples of clinically relevant interactions with ADs have been chosen. With regard to pharmacodynamic interactions, the serotonin syndrome, the risk of bleeding under SSRI therapy, and the corrected Q-T interval prolongation are discussed in this review. The inhibitory effects of new-generation ADs on CYP enzymes show great variability and might be relevant for prescription recommendations in elderly patients and in patients with polypharmacy. The CYP-enzyme-inducing effect of St. John's wort, a popular over-the-counter herbal drug, may lead to decreased plasma levels of CYP substrates. When comparing prescription data and observed adverse drug events, there is fortunately a safety gap between the number of potential drug-drug interactions and the number of clinically observed side effects due to drug-drug interactions.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / pharmacokinetics
  • Antidepressive Agents / pharmacology*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug Interactions
  • Enzyme Induction / drug effects
  • Enzyme Inhibitors / pharmacology
  • Hemorrhage / chemically induced
  • Humans
  • Long QT Syndrome / chemically induced
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / pharmacokinetics
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin Syndrome / chemically induced


  • Antidepressive Agents
  • Enzyme Inhibitors
  • Serotonin Uptake Inhibitors
  • Cytochrome P-450 Enzyme System