What is the difference between Celexa (citalopram) and Lexapro (escitalopram)?

Differences Between Celexa (Citalopram) and Lexapro (Escitalopram)

Lexapro (escitalopram) is more effective than Celexa (citalopram) for treating depression, particularly severe depression, while having a similar safety profile but with fewer drug interactions. 1

Chemical Differences

• Structure: Escitalopram is the S-enantiomer (single isomer) of racemic citalopram, while citalopram contains both S and R enantiomers 2
• Potency: Escitalopram is approximately 30 times more potent than the R-enantiomer at the serotonin transporter 3
• Binding mechanism: Escitalopram has both orthosteric and allosteric binding properties at the serotonin transporter, which may explain its enhanced efficacy compared to citalopram 4

Efficacy Differences

• Overall effectiveness: Escitalopram demonstrates superior efficacy compared to citalopram, especially in severe depression 1
• Speed of onset: Escitalopram shows clinically relevant and statistically significant superiority to placebo treatment earlier than citalopram 3
• Response rates: In severe depression, escitalopram has significantly higher response rates (56%) compared to citalopram (41%) 1

Safety and Tolerability

• QT prolongation: Both medications carry risks of QT prolongation, with specific dosing limitations:

  • Citalopram: FDA boxed warning not to exceed 40 mg per day (20 mg in adults over 60) 5
  • Escitalopram: Also associated with QT prolongation but without the same strict dosing limitations 5

• Sexual side effects: Both medications can cause sexual dysfunction, but escitalopram shows a trend toward increased risk compared to some other antidepressants 5

• Common side effects: For escitalopram, the most common adverse events include nausea, insomnia, ejaculation disorder, diarrhea, dry mouth, and somnolence, with only nausea occurring in >10% of patients 3

Pharmacokinetic Differences

• Half-life: Escitalopram has a half-life of 27-33 hours, consistent with once-daily dosing 6
• Drug interactions: Escitalopram has fewer drug interaction issues compared to citalopram 4
• Metabolism: Both are metabolized by CYP2C19, CYP2D6, and CYP3A4, but escitalopram has negligible inhibitory effects on CYP isoenzymes, suggesting a lower potential for drug-drug interactions 6

Dosing Considerations

• Citalopram dosing: 20-40 mg per day, with dose limitations due to QT prolongation risk 5
• Escitalopram dosing: 10-20 mg per day 5
• Renal/hepatic impairment:
  • Citalopram: Dose adjustment recommended in hepatic impairment 5
  • Escitalopram: No dosage adjustment necessary in hepatic impairment or elderly patients 6

Clinical Selection Factors

• For severe depression: Escitalopram is preferred due to demonstrated superior efficacy 1
• For patients with multiple medications: Escitalopram may be preferred due to fewer drug interactions 4
• For elderly patients: Both medications require caution, but escitalopram may have fewer pharmacokinetic changes in elderly patients 6

Special Populations

• Breastfeeding: Both medications transfer into breast milk, but potential adverse effects in infants have been documented more often with citalopram than with some other SSRIs 5
• Pregnancy: Both medications carry similar risks during pregnancy, including potential association with persistent pulmonary hypertension of the newborn when used after the 20th week of gestation 5

Cost Considerations

• Generic availability: Both medications are available as generics, with citalopram typically being less expensive 5
• Cost-effectiveness: Despite higher acquisition costs, pharmacoeconomic models suggest escitalopram's greater efficacy may offset the price difference compared to generic citalopram 7

When choosing between these medications, consider the patient's depression severity, potential for drug interactions, and specific risk factors for side effects such as QT prolongation.