Zoloft (Sertraline) Dosing for Anxiety and Depression
Start sertraline at 50 mg once daily for depression and obsessive-compulsive disorder; for panic disorder, PTSD, and social anxiety disorder, begin at 25 mg daily for one week, then increase to 50 mg daily. 1
Standard Adult Dosing
Depression and OCD
- Initial dose: 50 mg once daily (morning or evening) 1
- Therapeutic range: 50–200 mg/day 1
- Increase dose in 50 mg increments at intervals of at least 1 week (due to sertraline's 24-hour elimination half-life) 1
- 50 mg/day is the optimal dose when balancing efficacy and tolerability for most patients 2
Panic Disorder, PTSD, and Social Anxiety Disorder
- Initial dose: 25 mg once daily for 1 week 1
- Then increase to 50 mg once daily 1
- Maximum dose: 200 mg/day 1
- For panic disorder specifically, effective dosing ranges from 50–175 mg/day 3
Elderly Patients (≥60 Years)
No dose reduction is required for elderly patients based solely on age. 4, 5, 2
- Start at the same initial dose as younger adults: 50 mg/day for depression/OCD or 25 mg/day for anxiety disorders 1, 2
- Sertraline clearance is approximately 40% lower in elderly patients, but steady-state is achieved after 2–3 weeks 1
- Unlike other SSRIs, sertraline does not require altered dose recommendations in the elderly 2
- Sertraline is well-tolerated in elderly patients and lacks the marked anticholinergic effects of tricyclic antidepressants 5
Hepatic Impairment
Use a lower or less frequent dose in patients with liver disease. 1
- In patients with mild hepatic impairment (Child-Pugh 5–8), sertraline clearance is reduced, resulting in approximately 3-fold greater exposure 1
- Start at a reduced dose and increase cautiously 1
- Effects in moderate-to-severe hepatic impairment have not been studied; approach with extreme caution 1
Renal Impairment
No dose adjustment is needed for renal impairment, including patients on hemodialysis. 1
- Sertraline pharmacokinetics are unaffected by renal impairment (including CLcr 10–60 mL/min and hemodialysis) 1
- Excretion of unchanged drug in urine is a minor route of elimination 1
Titration and Monitoring
Dose Escalation
- Wait at least 1 week between dose increases due to sertraline's 24-hour half-life 1
- Patients not responding to 50 mg/day may benefit from increases up to maximum 200 mg/day 1
- Steady-state plasma concentrations are reached after approximately 7 days of once-daily dosing 6
Time to Clinical Effect
- Allow 4–8 weeks at therapeutic dose before determining treatment adequacy 4
- A full therapeutic trial requires at least 4–8 weeks 4
Maintenance Treatment
- For major depressive disorder, continue treatment for several months or longer beyond acute episode response 1
- In relapse-prevention studies, sertraline demonstrated statistically significantly lower relapse rates compared to placebo over 44 weeks 1
Administration Considerations
- Administer once daily, morning or evening (timing does not affect efficacy) 1
- Sertraline is slowly absorbed with peak plasma concentrations at 6–8 hours 6
- Highly protein-bound (98%) but does not displace warfarin or propranolol 1
Tolerability Profile
- Most common adverse events: dry mouth, headache, diarrhea, nausea, insomnia, somnolence 5
- Minimal anticholinergic activity and essentially devoid of cardiovascular effects 7
- Does not impair psychomotor performance or potentiate alcohol effects 6
- Lower potential for drug interactions compared to paroxetine, fluoxetine, and fluvoxamine (weak CYP450 inhibitor) 5, 6
Critical Clinical Pearls
- Sertraline has the least effect on metabolism of other medications compared to other SSRIs 4
- No dosage adjustments needed based on age alone, making it particularly suitable for elderly patients 2
- When discontinuing, taper over 10–14 days minimum to limit withdrawal symptoms 4
- Plasma concentrations are linearly related to dose 6