Citalopram vs Escitalopram

## Overview

Citalopram and escitalopram are parent compound and active enantiomer, respectively. Escitalopram (the S-enantiomer of citalopram) is approximately twice as potent per milligram and has been extensively compared to citalopram in clinical trials.

## Mechanism of Action

Both inhibit SERT via the primary binding site. Escitalopram additionally occupies an allosteric secondary binding site on SERT, potentially slowing dissociation from the primary site and enhancing net SERT occupancy at equivalent doses. The R-enantiomer in citalopram is pharmacologically inactive at SERT but may interfere with escitalopram's allosteric binding.

## Pharmacokinetics

Citalopram: half-life ~35 h, CYP2C19 (major) + CYP3A4, CYP2D6 (minor), minimal inhibitor. Escitalopram: half-life 27–32 h, similar metabolism. Both have ~80% bioavailability and minimal food effects. Both subject to 2011 FDA QTc restriction (citalopram 40 mg; escitalopram 20 mg).

## Pharmacodynamics and Clinical Efficacy

Escitalopram 10 mg is approximately equivalent to citalopram 20 mg for SERT occupancy. Head-to-head trials (e.g., Moore et al., 2005) generally show escitalopram superior to citalopram in response and remission rates, though effect sizes are modest. Escitalopram ranked higher in Cipriani 2018.

## Key Takeaways

- Escitalopram is the isolated active S-enantiomer; twice as potent per mg
- Escitalopram has allosteric SERT binding advantage
- Both have QTc limitations (20 mg escitalopram ≈ 40 mg citalopram limit)
- Escitalopram preferred for its slightly superior efficacy and tolerability
- Cost: citalopram may be cheaper; both widely generic