What is the recommended sertraline dosing regimen for adult patients with post‑traumatic stress disorder, including starting dose, titration schedule, maximum dose, and dose adjustments for elderly or hepatic impairment?

Sertraline Dosing for PTSD

Starting Dose and Initial Titration

For adult patients with PTSD, initiate sertraline at 25 mg once daily for the first week, then increase to 50 mg once daily. This approach allows assessment of tolerability before reaching the therapeutic dose 1, 2.

• Sertraline can be administered at any time of day (morning or evening), though consistency in timing is recommended 1
• The 25 mg starting dose serves as a "test dose" to minimize initial anxiety or agitation that SSRIs can sometimes cause 1
• After 3–7 days at 25 mg, increase to 50 mg daily, which represents the minimum effective dose for PTSD 1, 2

Therapeutic Dose Range and Titration Schedule

The therapeutic range for PTSD is 50–200 mg/day, with most patients responding to 100–150 mg daily 1, 2.

• If inadequate response after 2–4 weeks at 50 mg, increase by 25–50 mg increments every 1–2 weeks 1
• In the pivotal PTSD trial, flexible dosing of 50–200 mg/day produced a 60% responder rate versus 38% for placebo 2
• Maximum dose is 200 mg/day; doses above this threshold do not provide additional benefit 1, 2
• Allow at least 8 weeks at the optimal dose before concluding treatment failure 1

Expected Timeline for Response

Statistically significant improvement may occur within 2 weeks, with clinically meaningful response typically evident by week 6, and maximal benefit by week 12 or later 1.

• The CAPS-2 (Clinician-Administered PTSD Scale) showed significantly steeper improvement slopes for sertraline versus placebo starting early in treatment 2
• Quality of life improvements are progressive and sustained over more than 1 year of treatment 3
• Continue treatment for at least 4–12 months after achieving response to prevent relapse 1

Dose Adjustments for Special Populations

Elderly Patients (≥60 years)

No age-based dose reduction is required for elderly patients unless hepatic impairment is present 1, 4.

• Standard adult dosing (50–200 mg/day) applies to elderly patients 1, 4
• Sertraline is particularly well-suited for elderly patients due to lack of anticholinergic effects and minimal cytochrome P450 interactions 1, 4
• Pharmacokinetics in elderly patients are similar to younger adults, eliminating the need for routine dose adjustment 4, 5

Hepatic Impairment

Reduce the dose and slow titration in patients with hepatic disease 1.

• Consider starting at 25 mg and titrating more cautiously than in patients with normal hepatic function 1
• Monitor closely for adverse effects, as sertraline undergoes hepatic metabolism 5

Renal Impairment

No dose adjustment is needed for renal impairment 1, 5.

• Sertraline pharmacokinetics are not significantly altered by renal dysfunction 5

Critical Safety Monitoring

Monitor closely for suicidal thinking and behavior, especially during the first months of treatment and following dose adjustments 1.

• The pooled absolute rate for suicidal ideation is 1% for antidepressants versus 0.2% for placebo (Number Needed to Harm = 143) 1
• All SSRIs carry a boxed warning for suicidal thinking and behavior through age 24 years 1
• Weekly monitoring during dose adjustments is recommended, particularly in younger patients 1

Watch for serotonin syndrome, especially when combining with other serotonergic agents 1.

• Symptoms include mental status changes, neuromuscular hyperactivity, and autonomic instability 1
• Monitor particularly within the first 24–48 hours after starting or increasing the dose 1
• Sertraline is contraindicated with MAOIs; allow at least 14 days between discontinuing an MAOI and starting sertraline 1

Common Adverse Effects

The most frequently reported adverse events in PTSD trials were insomnia (35%), diarrhea (28%), nausea (23%), fatigue (13%), and decreased appetite (12%) 2.

• Most adverse effects emerge within the first few weeks and are dose-related 1
• Sertraline was well tolerated with only a 9% discontinuation rate due to adverse events versus 5% for placebo 2
• Other common effects include headache, dizziness, sweating, and sexual dysfunction 1, 4

Discontinuation Protocol

Never stop sertraline abruptly; taper gradually over a minimum of 2–4 weeks for short-term therapy, or several months for long-term therapy 1.

• Sertraline is associated with discontinuation syndrome characterized by dizziness, fatigue, myalgias, headaches, nausea, insomnia, and sensory disturbances 1
• If moderate to severe withdrawal symptoms occur, reinstate the previous dose and slow the taper rate 1
• Hold at the current dose for an additional 1–2 weeks before attempting further reduction 1

Common Pitfalls to Avoid

Do not increase the dose too rapidly – allow adequate trial duration (2–4 weeks minimum) at each dose level before escalating 1.

Do not underdose – many patients require 100–150 mg/day for optimal PTSD symptom control, not just the 50 mg starting dose 1, 2.

Do not discontinue prematurely – an adequate trial requires 8 weeks at the optimal dose before concluding ineffectiveness 1.

Do not combine with MAOIs or use within 14 days of MAOI discontinuation – this combination is absolutely contraindicated due to serotonin syndrome risk 1.