Half-Life of Lexapro (Escitalopram)
The elimination half-life of escitalopram (Lexapro) is approximately 27-32 hours, which supports once-daily dosing and results in steady-state plasma concentrations within approximately one week of treatment. 1
Pharmacokinetic Profile
- Terminal elimination half-life: The FDA-approved labeling specifies a mean terminal half-life of about 27-32 hours in young healthy subjects 1
- Time to steady state: With once-daily dosing, steady-state plasma concentrations are achieved within approximately one week (7-10 days) 1, 2
- Accumulation at steady state: The extent of accumulation in plasma is 2.2-2.5 times the plasma concentrations observed after a single dose 1
Age-Related Variations
- Elderly patients (≥65 years): The half-life is increased by approximately 50% compared to younger subjects, though Cmax remains unchanged 1. This pharmacokinetic difference supports the recommended dose reduction to 10 mg/day in elderly patients 1
- Adolescents (12-17 years): Following multiple dosing, the elimination half-life is similar to that in adults, requiring no dosage adjustment 1
Clinical Implications of the Half-Life
- Once-daily dosing: The 27-32 hour half-life is consistent with and supports once-daily administration 2, 3
- Discontinuation considerations: Unlike shorter-acting SSRIs such as paroxetine (which has a moderate half-life and requires gradual tapering over 10-14 days 4), escitalopram's longer half-life may result in a more gradual decline in plasma levels upon discontinuation
- Time to therapeutic effect: The relatively long half-life means that full steady-state concentrations—and potentially maximal therapeutic effects—may not be achieved until 7-10 days of consistent dosing 2
Comparison to Racemic Citalopram
- Citalopram half-life: The racemic mixture has a reported half-life of approximately 33 hours 5, which is similar to escitalopram's 27-32 hour half-life 1
- Metabolite considerations: The principal metabolite S-demethylcitalopram (S-DCT) is present at approximately one-third the level of escitalopram but is a weak inhibitor of serotonin reuptake and does not contribute significantly to therapeutic activity 1, 2
Absorption and Distribution Characteristics
- Time to peak concentration: Maximum plasma concentrations occur at approximately 3-4 hours after oral administration 2, 6, or about 5 hours according to FDA labeling 1
- Bioavailability: Absolute bioavailability is high, with the systemic clearance of approximately 600 mL/min (or 31 L/h after IV administration) 1, 6
- Volume of distribution: The apparent volume of distribution is approximately 1,100 L (or about 20 L/kg), indicating wide tissue distribution 1, 6