, Volume 174, Issue 2, pp 163–176 | Cite as

Escitalopram versus citalopram: the surprising role of the R-enantiomer

  • Connie Sánchez
  • Klaus P. Bøgesø
  • Bjarke Ebert
  • Elin Heldbo Reines
  • Claus Braestrup



Citalopram is a racemate consisting of a 1:1 mixture of the R(−)- and S(+)-enantiomers. Non-clinical studies show that the serotonin reuptake inhibitory activity of citalopram is attributable to the S-enantiomer, escitalopram. A series of recent non-clinical and clinical studies comparing escitalopram and citalopram to placebo found that equivalent doses of these two drugs, i.e. containing the same amount of the S-enantiomer, showed better effect for escitalopram. These results suggested that the R-citalopram in citalopram inhibits the effect of the S-enantiomer.


To review the pharmacological and non-clinical literature that describes the inhibition of escitalopram by R-citalopram, as well as the implications of this inhibition for the clinical efficacy of escitalopram compared to citalopram.


The information in this review was gathered from published articles and abstracts.


In appropriate neurochemical, functional, and behavioural non-clinical experiments, escitalopram shows greater efficacy and faster onset of action than comparable doses of citalopram. The lower efficacy of citalopram in these studies is apparently due to the inhibition of the effect of the S-enantiomer by the R-enantiomer, possibly via an allosteric interaction with the serotonin transporter. Data from randomised clinical trials consistently show better efficacy with escitalopram than with citalopram, including higher rates of response and remission, and faster time to symptom relief.


The R-enantiomer present in citalopram counteracts the activity of the S-enantiomer, thereby providing a possible basis for the pharmacological and clinical differences observed between citalopram and escitalopram.


Escitalopram Citalopram R-citalopram Enantiomers Stereochemistry SSRI Serotonin transporter Depression Panic disorder Antidepressant 



The authors acknowledge Yaron Y. Levy for assistance in preparing the manuscript.


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Connie Sánchez
    • 1
    • 2
  • Klaus P. Bøgesø
    • 1
  • Bjarke Ebert
    • 1
  • Elin Heldbo Reines
    • 1
  • Claus Braestrup
    • 1
  1. 1.Research and DevelopmentH. Lundbeck A/SValby CopenhagenDenmark
  2. 2.Neuropharmacological ResearchH. Lundbeck A/SValby CopenhagenDenmark

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