Best SSRI for PTSD
Sertraline is the best SSRI for PTSD, with the strongest evidence base and FDA approval specifically for this indication. 1, 2
First-Line Recommendation: Sertraline
Sertraline should be initiated at 25 mg daily for one week, then increased to 50 mg daily, with a target range of 50-200 mg/day. 1 This medication has:
- FDA approval specifically for PTSD 2
- The most extensive evidence base with multiple large placebo-controlled trials showing 60% responder rates compared to 38% for placebo 3
- Superior efficacy across all three PTSD symptom clusters: re-experiencing, avoidance/numbing, and hyperarousal 4, 5
- Favorable tolerability with only 9% discontinuation due to adverse events 3
- Lower adverse effect rates in older adults compared to paroxetine and fluoxetine 1
Second-Line Option: Paroxetine
Paroxetine at 20 mg daily is an alternative first-line choice if sertraline is not tolerated. 1, 6 However, it has important limitations:
- FDA-approved for PTSD with demonstrated efficacy in multiple trials 6
- Higher risk of discontinuation syndrome characterized by dizziness, fatigue, nausea, and sensory disturbances 1
- Should be avoided in older adults due to higher adverse effect rates 1
- No clear benefit for doses above 20 mg/day 6
Off-Label Alternative: Fluoxetine
Fluoxetine (5-60 mg/day) has favorable evidence but lacks FDA approval for PTSD 1. This medication should generally be avoided in older adults due to higher rates of adverse effects. 1
Treatment Duration and Monitoring
Evaluate treatment response after 8 weeks of SSRI therapy. 1 Expected outcomes show 53-85% of participants classified as treatment responders in controlled trials 1.
Continue acute treatment for at least 6-12 months after symptom remission, as discontinuation leads to 26-52% relapse rates with sertraline 1. This relapse rate is substantially higher than after completing trauma-focused psychotherapy 7.
Critical Integration with Psychotherapy
Trauma-focused psychotherapy (Prolonged Exposure, Cognitive Processing Therapy, or EMDR) should be considered first-line treatment, with 40-87% of patients no longer meeting PTSD criteria after 9-15 sessions 1, 7. These therapies show:
- Lower relapse rates compared to medication discontinuation 7
- Equal effectiveness regardless of trauma type, childhood abuse history, or comorbidities 7
- No increased dropout rates even in complex presentations 7
Medication should be reserved for when psychotherapy is unavailable, refused by the patient, or residual symptoms persist after psychotherapy. 7
Medications to Absolutely Avoid
Benzodiazepines are contraindicated in PTSD, particularly in patients with substance use history, with evidence showing 63% of patients receiving benzodiazepines developed PTSD at 6 months compared to only 23% receiving placebo 7. Cannabis and cannabis-derived products should also not be used 1.
Common Adverse Effects and Management
Most common adverse events with sertraline include 3:
- Insomnia (35% vs 22% placebo)
- Diarrhea (28% vs 11% placebo)
- Nausea (23% vs 11% placebo)
- Fatigue (13% vs 5% placebo)
- Decreased appetite (12% vs 1% placebo)
Sexual dysfunction can occur in adolescents and adults, including erectile dysfunction, delayed ejaculation, and anorgasmia 1. Serotonin syndrome risk requires at least 14 days washout when switching from MAOIs and caution when combining with other serotonergic agents 1.
Special Populations
For patients with comorbid depression, sertraline remains the preferred choice as 44% of PTSD patients in sertraline trials who had secondary depressive disorder showed significant improvement on both PTSD and depression measures 1.
For patients with substance use history, SSRIs (sertraline, paroxetine, or fluoxetine) are the exclusive pharmacological options, with benzodiazepines absolutely contraindicated 7.