What is the recommended dosing for sertraline (Selective Serotonin Reuptake Inhibitor) in the treatment of Major Depressive Disorder (MDD)?

Sertraline Dosing for Major Depressive Disorder

Start sertraline at 50 mg once daily, which is both the initial and optimal therapeutic dose for most adults with MDD. 1

Initial Dosing

• Begin with 50 mg once daily for adults with major depressive disorder 1
• Administer as a single daily dose, either morning or evening 1
• No titration period is required—start directly at the therapeutic dose 1, 2

The FDA-approved labeling establishes 50 mg/day as the standard starting dose, which differs from panic disorder, PTSD, and social anxiety disorder where a 25 mg starting dose with one-week titration is recommended 1. This 50 mg starting dose represents the optimal balance between efficacy and tolerability for depression specifically 2, 3.

Dose Adjustments

• For patients not responding adequately after 2-4 weeks, increase in 50 mg increments 1
• Maximum dose: 200 mg/day 1
• Wait at least 1 week between dose changes due to sertraline's 24-hour elimination half-life 1

Clinical trials demonstrated effectiveness across the 50-200 mg/day range, though no clear dose-response relationship was established for MDD 1. A fixed-dose study showed that 50 mg once daily was as effective as higher dosages (100 mg or 200 mg) with fewer side effects and discontinuations 3. However, approximately 38% of patients do not achieve treatment response at initial doses, and 54% do not achieve remission, supporting the rationale for dose escalation in non-responders 4.

Special Populations

Elderly Patients (≥60 years)

• Use the same 50 mg starting dose—no age-based adjustment needed 1, 5, 6
• Dose range remains 50-200 mg/day 5, 6
• Sertraline lacks the anticholinergic effects problematic in elderly patients and has low drug interaction potential, making it particularly suitable for this population 5, 6

Pediatric Patients (OCD only, not MDD)

• Ages 6-12: Start 25 mg once daily 1
• Ages 13-17: Start 50 mg once daily 1
• Consider lower body weight when advancing doses 1

Maintenance Treatment

• Continue effective dose for 4-12 months minimum after acute episode response 4
• Sertraline maintains antidepressant efficacy for at least 44 weeks following initial 8-week treatment (mean effective dose 70 mg/day) 1
• For recurrent depression (≥2 prior episodes), consider prolonged or indefinite treatment 4

Clinical Context

The American College of Physicians guidelines confirm that second-generation antidepressants, including sertraline, show no clinically significant differences in efficacy for acute-phase MDD 4. Sertraline demonstrated similar effectiveness to fluoxetine, paroxetine, citalopram, and venlafaxine in head-to-head trials 4. However, limited evidence suggests sertraline may have advantages for patients with melancholia or psychomotor agitation 4.

Common Pitfalls to Avoid

• Do not start at 25 mg for MDD (this lower starting dose is only for panic disorder, PTSD, and social anxiety disorder) 1
• Do not increase doses more frequently than weekly intervals—sertraline's pharmacokinetics require this spacing 1
• Do not assume higher doses are always better—50 mg is often sufficient and better tolerated 2, 3
• Monitor for common adverse effects including nausea, diarrhea, insomnia, and sexual dysfunction, which may warrant dose adjustment 4