Sertraline Half-Life
Sertraline has an elimination half-life of approximately 26 hours (range 22-36 hours), allowing for once-daily dosing. 1, 2
Pharmacokinetic Details
The FDA-approved drug label specifies that the plasma terminal elimination half-life of sertraline ranges from 22 to 36 hours in adults, with steady-state achieved after approximately 1 week (7 days) of daily dosing. 1
Active Metabolite Considerations
- N-desmethylsertraline, the primary metabolite, has a significantly longer half-life of 62 to 104 hours, though it is substantially less pharmacologically active than the parent compound. 1
- This metabolite accumulates to greater concentrations in plasma than sertraline itself at steady state, exhibiting 5 to 9-fold increases in pharmacokinetic parameters between day 1 and day 14. 1
Population-Specific Variations
Pediatric Patients
- Children aged 6-12 years show a mean half-life of 26.2 hours. 1
- Adolescents aged 13-17 years demonstrate a mean half-life of 27.8 hours. 1
- These values are comparable to adults (27.2 hours), though pediatric patients metabolize sertraline with slightly greater efficiency when adjusted for body weight. 1
Elderly Patients
- Sertraline plasma clearance is approximately 40% lower in elderly patients compared to younger individuals, suggesting steady-state is achieved after 2 to 3 weeks rather than the typical 1 week. 1
- Despite reduced clearance, the elimination half-life remains approximately 26 hours, similar to younger adults. 3
Hepatic Impairment
- Patients with mild liver impairment (Child-Pugh scores 5-8) show approximately 3-fold greater sertraline exposure due to reduced clearance, necessitating lower or less frequent dosing. 1
Renal Impairment
- The half-life and pharmacokinetics remain unaltered in patients with mild to severe renal impairment, including those on hemodialysis, as sertraline is extensively metabolized and renal excretion of unchanged drug is minimal. 1
Clinical Implications for Discontinuation
- Due to sertraline's relatively short half-life compared to fluoxetine, it requires careful attention during discontinuation to avoid withdrawal symptoms. 4
- When switching to an MAOI, a washout period of 5-7 days minimum (potentially extending to 2 weeks) is recommended to prevent serotonin syndrome. 5
- At low doses, twice-daily dosing may be required in youth due to the shorter half-life relative to fluoxetine. 4