Best SSRI for PTSD
Sertraline and paroxetine are the first-line SSRIs for PTSD treatment, as they are the only FDA-approved medications for this indication and have the strongest evidence base from large-scale controlled trials. 1, 2, 3
First-Line SSRI Recommendations
Sertraline should be initiated at 25 mg daily for one week, then increased to 50 mg daily, with the option to titrate further based on response 1. Sertraline is FDA-approved for PTSD treatment in adults and demonstrated efficacy in two 12-week placebo-controlled trials, with 53-85% of participants classified as treatment responders 1, 2. The medication has proven efficacy in maintaining response during continuation treatment, with relapse rates of 26-52% upon discontinuation 1.
Paroxetine should be started at 20 mg daily 1, 3. It is also FDA-approved for PTSD and demonstrated superiority over placebo in multiple 12-week controlled trials, with doses of 20 mg and 40 mg both showing significant efficacy 3. In PTSD trials, 20 mg was effective without clear additional benefit from higher doses 3.
Why These Two Stand Out
Both sertraline and paroxetine are the only SSRIs with FDA approval specifically for PTSD, based on rigorous placebo-controlled trials demonstrating efficacy across all three PTSD symptom clusters: reexperiencing/intrusion, avoidance/numbing, and hyperarousal 2, 3, 4. They have been the most extensively studied SSRIs for PTSD with the largest number of double-blind, placebo-controlled trials 4, 5.
Alternative SSRI Options
Fluoxetine has a dose range of 5-60 mg/day with evidence supporting efficacy at doses as low as 5 mg daily, though common dosing includes increasing to 40-60 mg/day after 1 week for optimal effect 1. However, fluoxetine should generally be avoided in older adults due to higher rates of adverse effects 1. While fluoxetine has been studied for PTSD, it lacks FDA approval for this indication 4.
Citalopram has limited but favorable data suggesting a potential role in PTSD treatment 1, 6. An 8-week open-label trial showed significant reduction in all core PTSD symptoms with doses of 20-40 mg daily, with 9 of 11 completers classified as responders 6. However, daily doses should not exceed 40 mg due to risk of QT prolongation, Torsade de Pointes, and sudden death 1.
Escitalopram (the S-enantiomer of citalopram) showed promise in a 12-week open-label trial with doses of 10-20 mg daily, demonstrating significant improvements in CAPS scores and 45% of patients much or very much improved 7. However, it lacks controlled trial data and FDA approval for PTSD 7.
Treatment Duration and Response Assessment
Evaluate treatment response after 8 weeks of SSRI therapy 1. The best-fitting model for SSRI response shows clinically significant improvement by week 6 and maximal improvement by week 12 or later 8. Continue acute treatment for at least 6-12 months after symptom remission to prevent relapse 1.
Critical Considerations Before Starting SSRIs
Trauma-focused psychotherapy should be considered first-line treatment, with Prolonged Exposure, Cognitive Processing Therapy, or EMDR showing 40-87% of patients no longer meeting PTSD criteria after 9-15 sessions 1. This is important context when deciding whether to initiate pharmacotherapy.
Common Pitfalls and Adverse Effects
Sexual dysfunction can occur with SSRIs, including erectile dysfunction, delayed ejaculation, and anorgasmia 1. Gastrointestinal disturbances are the most common adverse effects, with nausea and vomiting being the most common reasons for discontinuation 1.
Discontinuation syndrome is particularly associated with paroxetine, but also affects sertraline, characterized by dizziness, fatigue, nausea, and sensory disturbances 1. Taper slowly when discontinuing, especially with paroxetine.
Serotonin syndrome risk exists when combining SSRIs with MAOIs or multiple serotonergic agents, requiring at least 14 days washout between medications 1.
Medications to Absolutely Avoid
Benzodiazepines are contraindicated in PTSD, particularly in patients with substance use history, due to high abuse potential and evidence of worsening outcomes 1, 4. Despite encouraging case reports, they were ineffective in controlled trials and may promote or worsen PTSD 4.
Cannabis and cannabis-derived products should not be used for PTSD treatment 1.