Escitalopram vs Citalopram: Key Differences
Escitalopram is the therapeutically active S-enantiomer of citalopram and demonstrates superior efficacy at half the dose, with faster onset of action and better response rates, particularly in severe depression. 1, 2, 3
Pharmacologic Distinction
- Escitalopram is the isolated S-enantiomer that carries the therapeutic potential of citalopram, while citalopram is a racemic mixture containing equal amounts of both S- and R-enantiomers 1, 2
- The R-enantiomer in citalopram is essentially pharmacologically inactive 4
- Escitalopram is the most selective SSRI with almost no significant affinity to other tested receptors 1
Clinical Efficacy Differences
Dose Equivalence and Potency
- Escitalopram 10-20 mg/day is therapeutically equivalent to citalopram 20-40 mg/day, meaning escitalopram achieves the same effect at half the dose 5, 2, 4
Speed of Onset
- Escitalopram separates from placebo statistically at week 1 for all efficacy measures (MADRS, CGI-I, anxiety symptoms), while citalopram requires 4-6 weeks to show statistical separation from placebo 2
- This faster onset translates to earlier symptom relief in clinical practice 2, 6
Magnitude of Effect
- In pooled analysis of 506 severely depressed patients (MADRS ≥30), escitalopram produced significantly greater improvement than citalopram (mean MADRS change: -17.3 vs -13.8, p=0.003) 3
- Response rates were significantly higher with escitalopram (56% vs 41%, p=0.007) 3
- Remission rates showed borderline superiority for escitalopram (43% vs 33%, p=0.07) 3
Anxiety Symptoms
- Escitalopram demonstrates significant improvement in anxiety symptoms (MADRS inner tension item) as early as week 1 (p<0.05), with even greater significance by week 2 (p<0.001) 6
- Both medications improve anxiety, but escitalopram's earlier onset is clinically meaningful for patients with comorbid anxiety 2, 6
Guideline Recommendations
- Both escitalopram and citalopram are listed as preferred first-line agents by the American Family Physician guidelines due to favorable adverse effect profiles 5
- The American College of Physicians recommends escitalopram as preferred initial treatment for patients with depression and anxiety 7
- Escitalopram is FDA-approved for major depressive disorder in both adults and adolescents (ages 12-17), as well as generalized anxiety disorder 8
Dosing Considerations
Escitalopram
- Starting dose: 10 mg daily 5, 8
- Maximum dose: 20 mg daily 5, 8
- No dose adjustment needed for renal impairment; no adjustment for hepatic impairment 5
Citalopram
- Starting dose: 20 mg daily 5
- Maximum dose: 40 mg daily (lower in elderly and hepatic impairment due to QTc concerns) 5
- Consider dose reduction in hepatic disease 5
Safety Profile
- Both medications share similar tolerability profiles with mild, transient nausea and potential ejaculatory dysfunction 1, 4
- Citalopram has greater QTc prolongation concerns at higher doses, which led to FDA dose restrictions 5
- Escitalopram is generally better tolerated compared to other antidepressants 1
Clinical Bottom Line
For treatment-naive patients with major depressive disorder, especially those with severe depression (MADRS ≥30) or comorbid anxiety, escitalopram offers superior efficacy at lower doses with faster onset of action compared to citalopram. 2, 3 The evidence supporting escitalopram's advantages is strongest in severe depression, where the magnitude of benefit is clinically meaningful, not just statistically significant 3. While both are acceptable first-line options per guidelines 5, the pharmacologic and clinical data favor escitalopram when choosing between these two specific agents 1, 2, 3.