What is the difference between escitalopram (Lexapro) and citalopram (Celexa) in terms of efficacy and side effects?

Escitalopram vs Citalopram: Clinical Comparison

Escitalopram is the preferred choice over citalopram for most patients with depression and anxiety disorders due to its superior efficacy, faster onset of action, lower drug interaction potential, and reduced cardiac risk. 1, 2, 3

Efficacy Differences

Escitalopram demonstrates statistically and clinically superior efficacy compared to citalopram, though the American College of Physicians notes the effect size is modest (relative benefit 1.14,95% CI 1.04-1.26). 1 However, this statistical advantage translates into meaningful clinical differences:

• Escitalopram separates from placebo by week 1, while citalopram requires 4-6 weeks to demonstrate statistical superiority over placebo. 1, 4, 5
• Response rates at 2 weeks are 58% for escitalopram (10mg) versus 49% for citalopram (20mg), with remission rates at 4 weeks of 74% versus 65% respectively. 6
• The therapeutic activity of citalopram resides primarily in the S-enantiomer (escitalopram), while the R-enantiomer is approximately 30-fold less potent. 7, 8

Drug Interaction Profile

Escitalopram has the lowest propensity for drug-drug interactions among all SSRIs due to minimal effects on cytochrome P450 isoenzymes, making it the safest choice for patients on multiple medications. 1, 2, 3

• Citalopram has moderate CYP450 interactions, particularly affecting drugs metabolized by CYP2D6. 1
• This advantage is particularly important in elderly patients and those with medical comorbidities requiring polypharmacy. 1, 3

Cardiac Safety Considerations

Citalopram carries significantly higher cardiac risk than escitalopram:

• The FDA issued a 2012 boxed warning limiting citalopram to maximum 40 mg/day (20 mg/day in adults >60 years) due to dose-dependent QT prolongation. 1
• Citalopram is associated with QT prolongation leading to Torsade de Pointes, ventricular tachycardia, and sudden death at higher doses. 1
• Escitalopram has lower risk of QT prolongation and presents a safer cardiac profile. 1, 3
• Avoid citalopram entirely in patients with long QT syndrome, cardiac disease, or those taking QT-prolonging medications. 1, 3

Tolerability and Side Effects

Both medications share common SSRI side effects (nausea, diarrhea, headache, insomnia, sexual dysfunction), but differ in their tolerability profiles:

• Escitalopram has lower discontinuation rates due to adverse events (45% reported adverse experiences versus 58% with citalopram). 6
• Escitalopram demonstrates lower risk of discontinuation syndrome compared to citalopram. 2, 3
• Only nausea occurs in >10% of escitalopram-treated patients, with no statistically significant difference from placebo in discontinuation rates at 10mg/day. 8

Dosing Considerations

Escitalopram requires half the dose of citalopram for equivalent therapeutic effect:

• Escitalopram: 10-20 mg/day (start 10mg) 1, 3
• Citalopram: 20-40 mg/day (start 20mg), with maximum 20mg/day in elderly 1, 3
• Both maintain once-daily dosing with half-lives of 27-32 hours. 8
• No dose adjustment needed for escitalopram in renal or hepatic disease, while citalopram requires consideration in hepatic impairment. 1

Special Populations

For elderly patients, escitalopram is the preferred agent due to its superior tolerability profile, lack of dose adjustment requirements, and absence of cardiac concerns at therapeutic doses. 1, 3

• Both medications are considered appropriate first-line agents, but paroxetine and fluoxetine should be avoided in elderly due to anticholinergic effects and agitation risk respectively. 1
• Both carry boxed warnings for suicidal thinking/behavior through age 24 (pooled absolute rate 1% versus 0.2% placebo). 2

Clinical Algorithm for Selection

Choose escitalopram as first-line unless:

1. Cost is prohibitive (citalopram is less expensive: $4 vs $10 monthly for generics) 1
2. Patient has previously responded well to citalopram specifically
3. Patient requires doses >20mg equivalent (then consider switching to different SSRI class)

Mandatory citalopram avoidance:

• Cardiac disease or QT prolongation risk factors 1, 3
• Age >60 years requiring doses >20mg 1
• Concomitant QT-prolonging medications 1
• Multiple drug interactions via CYP2D6 1

Monitoring Requirements

• Assess therapeutic response within 1-2 weeks of initiation (escitalopram should show early response). 3, 4
• Modify treatment if inadequate response by 6-8 weeks. 3
• Monitor for suicidality closely in first 1-2 months and after dose changes. 1, 2
• Baseline ECG recommended for citalopram in at-risk patients; not routinely required for escitalopram. 1