What are the evidence‑based selective serotonin reuptake inhibitors (SSRIs) for treating post‑traumatic stress disorder in an adult without contraindications?

Evidence-Based SSRIs for PTSD

Sertraline and paroxetine are the evidence-based SSRIs for PTSD, with both FDA-approved for this indication and supported by the strongest guideline recommendations. 1, 2, 3

First-Line SSRI Recommendations

The 2023 VA/DoD guidelines recommend sertraline, paroxetine, or venlafaxine (an SNRI) as first-line pharmacotherapy for PTSD. 1 These are the only medications with sufficient evidence to warrant recommendation, though psychotherapy remains preferred over pharmacotherapy. 1

Sertraline

• FDA-approved for PTSD treatment with efficacy established in two 12-week placebo-controlled trials 2
• Start at 25 mg daily for one week, then increase to 50 mg daily 4
• Demonstrated 53-85% treatment response rates in controlled trials 4
• Preferred over paroxetine in older adults due to lower adverse effect rates 4
• Continuation for 6-12 months after remission reduces relapse rates (26-52% relapse with discontinuation) 4, 5

Paroxetine

• FDA-approved for PTSD treatment with efficacy established in two 12-week placebo-controlled trials 3
• Initiate at 20 mg daily 4
• Equally effective as sertraline but carries higher risk of discontinuation syndrome (dizziness, fatigue, nausea, sensory disturbances) 4
• Should be avoided in older adults when sertraline is available 4

Critical Treatment Timeline

• Evaluate treatment response after 8 weeks of adequate-dose SSRI therapy 4
• Allow full 8-12 weeks before declaring treatment failure, as maximal benefit may take this long 5, 6
• Continue acute treatment for at least 6-12 months after symptom remission to prevent relapse 4, 5

Second-Line SSRI Options

Fluoxetine

• Not FDA-approved for PTSD but has supportive evidence from open-label and controlled studies 4, 5
• Dose range 5-60 mg/day, commonly increased to 40-60 mg/day after 1 week for optimal effect 4
• Avoid in older adults due to higher adverse effect rates compared to sertraline 4

Citalopram

• Limited but favorable data suggesting potential efficacy 7
• Maximum dose 40 mg daily due to QT prolongation risk, Torsade de Pointes, and sudden death 4
• Should only be considered when first-line agents have failed

Psychotherapy Should Be Prioritized

Trauma-focused psychotherapy (Prolonged Exposure, Cognitive Processing Therapy, or EMDR) is recommended over pharmacotherapy as first-line treatment. 1, 4 These therapies show 40-87% of patients no longer meeting PTSD criteria after 9-15 sessions, potentially superior to medication alone. 4

• Psychotherapy and pharmacotherapy can be initiated concurrently without waiting for stabilization 4
• Even patients with complex trauma and comorbid mood disorders benefit from trauma-focused treatment without prior stabilization 4

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, 5

Cannabis and cannabis-derived products should not be used for PTSD treatment. 1, 4

Common Pitfalls and Management

Sexual Dysfunction

• Occurs with all SSRIs, including erectile dysfunction, delayed ejaculation, and anorgasmia 4
• Consider switching to bupropion or mirtazapine if this becomes treatment-limiting

Gastrointestinal Effects

• Nausea and vomiting are the most common adverse effects and reasons for discontinuation 4
• Typically resolve within 1-2 weeks of continued treatment

Discontinuation Syndrome

• Particularly problematic with paroxetine, but also occurs with fluvoxamine and sertraline 4
• Taper gradually when discontinuing to minimize withdrawal symptoms

Serotonin Syndrome Risk

• Avoid combining SSRIs with MAOIs or multiple serotonergic agents 4
• Require at least 14-day washout period when switching between these medication classes

Treatment-Resistant PTSD

If SSRIs fail after adequate trial (8-12 weeks at therapeutic doses):

• Switch to venlafaxine (SNRI), which is also recommended by VA/DoD guidelines 1
• Consider augmentation with trauma-focused psychotherapy if not already implemented 4
• Prazosin can be added specifically for PTSD-associated nightmares (Level A recommendation) 1