What is the best Selective Serotonin Reuptake Inhibitor (SSRI) for treating Post-Traumatic Stress Disorder (PTSD)?

Best SSRI for PTSD

Sertraline and paroxetine are the first-line SSRIs for treating PTSD, as they are the only FDA-approved medications for this condition. 1, 2, 3

Evidence-Based Recommendation

The selection between sertraline and paroxetine should be guided by:

1. Efficacy: Both medications have demonstrated significant efficacy in reducing PTSD symptoms in multiple clinical trials

   • Sertraline has shown a 60% response rate compared to 38% for placebo 4
   • Paroxetine has demonstrated superiority over placebo in multiple studies 3

2. FDA Approval Status: Both sertraline and paroxetine have received FDA approval specifically for PTSD treatment 1, 2, 3

3. Side Effect Profile:

   • Sertraline: Common side effects include insomnia (35%), diarrhea (28%), nausea (23%), fatigue (13%), and decreased appetite (12%) 4
   • Paroxetine: May have more pronounced sedative effects and discontinuation symptoms

Treatment Algorithm

1. First choice: Start with sertraline

   • Initial dose: 25-50 mg daily
   • Target dose: 50-200 mg daily
   • Rationale: Generally better tolerated with fewer discontinuation symptoms 1

2. Alternative first choice: Paroxetine

   • Initial dose: 20 mg daily
   • Target dose: 20-40 mg daily
   • Consider when sleep disturbance is a prominent symptom due to more sedating properties

3. If inadequate response after 8-12 weeks of optimal dosing:

   • Switch to the alternative SSRI (paroxetine if started with sertraline, or vice versa)
   • OR consider venlafaxine as a second-line option (starting at 37.5 mg daily, target dose 225 mg daily) 1

Special Considerations

• For PTSD with prominent nightmares: Consider adding prazosin (starting at 1 mg at bedtime, average dose 3 mg) 5, 1

• For treatment-resistant cases: Consider augmentation with atypical antipsychotics 1, 6

• Duration of treatment: Continue medication for at least 12-24 months after achieving remission to prevent relapse 1

  • Relapse rates of 26-52% when medication is discontinued versus 5-16% when maintained on medication 5

Important Caveats

• Avoid benzodiazepines in PTSD as they may worsen outcomes 5, 6

• Monitor closely during the initial weeks of treatment for potential worsening of symptoms or suicidal ideation

• Recent research suggests that patient factors such as gender, trauma type, and time since trauma may influence treatment response 7

• While fluoxetine and citalopram have shown promise in some studies 6, 8, they lack the robust evidence base and FDA approval that sertraline and paroxetine have for PTSD treatment

By following this evidence-based approach, clinicians can optimize outcomes for patients with PTSD while minimizing adverse effects.