Are Citalopram and Escitalopram the Same?
No, citalopram and escitalopram are not the same medication—escitalopram is the isolated S-enantiomer of citalopram and demonstrates superior efficacy, faster onset of action, and fewer drug interactions than the racemic mixture. 1, 2
Chemical Relationship
- Citalopram is a racemic mixture containing equal amounts (1:1) of both S-enantiomer (escitalopram) and R-enantiomer (R-citalopram). 1, 3
- Escitalopram is the pure S-enantiomer extracted from citalopram, containing only the therapeutically active isomer. 1, 4
- The molecular formula for escitalopram oxalate is C20H21FN2O • C2H2O4 with a molecular weight of 414.40. 1
Why Escitalopram Performs Better
The R-enantiomer present in citalopram actively counteracts the therapeutic effects of the S-enantiomer through an allosteric interaction at the serotonin transporter. 3, 5
Mechanism of R-Enantiomer Interference:
- R-citalopram binds to an allosteric (secondary) site on the serotonin transporter and decreases escitalopram's binding effectiveness at the primary orthosteric site. 5
- In microdialysis studies, escitalopram increased extracellular serotonin levels in the frontal cortex and ventral hippocampus, but this effect was prevented by concomitant R-citalopram administration. 5
- Escitalopram was four times more potent than citalopram in suppressing firing activity of serotonin neurons in the dorsal raphe nucleus. 5
Clinical Efficacy Differences
Pooled analysis of three randomized controlled trials demonstrated that escitalopram separated from placebo after 1 week of treatment, while citalopram required 4-6 weeks to show statistical separation from placebo. 6
Key Clinical Advantages of Escitalopram:
- Higher response rates: More patients achieved ≥50% improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) scores with escitalopram versus citalopram. 6
- Faster onset: Escitalopram showed statistically significant improvements in all efficacy measures after 1 week, compared to 4-6 weeks for citalopram. 6
- Greater magnitude of effect: Escitalopram demonstrated superior efficacy at multiple time points throughout treatment. 6
Drug Interaction Profile
Escitalopram has the lowest propensity for drug-drug interactions among all SSRIs due to minimal effects on CYP450 isoenzymes, while citalopram has moderate interaction potential. 7, 8
- Citalopram/escitalopram may have the least effect on CYP450 isoenzymes compared with other SSRIs. 7
- Both medications can interact with drugs that prolong the QT interval, but citalopram carries a specific FDA boxed warning not to exceed 40 mg/day (or 20 mg/day in adults >60 years) due to dose-dependent QT prolongation risk. 7
Practical Prescribing Implications
When choosing between these medications, escitalopram offers approximately twice the potency of citalopram at equivalent S-enantiomer doses, with better tolerability and faster therapeutic response. 2, 4
Dosing Equivalence:
- Escitalopram 10 mg contains the same amount of active S-enantiomer as citalopram 20 mg. 6
- Escitalopram 20 mg is equivalent to citalopram 40 mg in S-enantiomer content. 6
Common Pitfall to Avoid:
- Do not assume these medications are interchangeable at the same milligram dose—escitalopram requires half the dose of citalopram to deliver equivalent amounts of the active S-enantiomer. 6