What is the best medication for a patient with post-traumatic stress disorder (PTSD) and anxiety?

Best Medication for PTSD and Anxiety

Sertraline is the recommended first-line medication for patients with both PTSD and anxiety, starting at 25 mg daily for one week, then increasing to 50 mg daily, with a target therapeutic dose of 50-200 mg/day. 1, 2

Why Sertraline is the Optimal Choice

• Sertraline is FDA-approved for both PTSD and panic disorder, making it uniquely positioned to address both conditions simultaneously in patients with comorbid presentations 2, 3

• The American Psychiatric Association specifically recommends sertraline as first-line treatment for both panic disorder and PTSD, with response rates of 53-85% in controlled trials, significantly outperforming placebo (32-62% response rate) 1

• Sertraline demonstrates superior relapse prevention compared to other SSRIs, with only 5-16% relapse when maintained on medication versus 26-52% when shifted to placebo 1

Dosing Strategy

• Start at 25 mg daily for the first week to minimize initial anxiety or agitation, which is particularly important in anxious patients 1, 4

• Increase to 50 mg daily after week 1, with flexible titration up to 200 mg/day based on response and tolerability 1, 2

• Single daily dosing is sufficient due to sertraline's 24-hour half-life 1

• Allow adequate time for response: statistically significant improvement may begin by week 2, but clinically significant improvement typically requires 6 weeks, with maximal benefit by week 12 4

Alternative First-Line Options

• Paroxetine (20-60 mg/day) is a reasonable second-line choice due to FDA approval for both PTSD and panic disorder, though it carries higher discontinuation syndrome risk 1, 3

• Venlafaxine (SNRI) has evidence for anxiety disorders and PTSD but ranks lower than SSRIs in overall tolerability and lacks FDA approval for panic disorder 1, 5

• Escitalopram (10-20 mg/day) or fluoxetine (20-40 mg/day) are reasonable third-line alternatives if both sertraline and paroxetine fail or are not tolerated 1

Critical Implementation: Combination with Psychotherapy

• Combining sertraline with cognitive behavioral therapy (CBT) provides superior outcomes to either treatment alone for both panic disorder and PTSD 1, 4

• A structured course of 12-20 CBT sessions targeting anxiety-specific cognitive distortions and exposure techniques is recommended 1, 4

• Individual CBT is preferred over group therapy for superior clinical and health-economic effectiveness 4

Treatment Duration

• Continue sertraline for at least 9-12 months after achieving remission to prevent relapse 1, 2

• The efficacy of sertraline in maintaining response has been demonstrated in placebo-controlled trials for up to 28 weeks following initial treatment response 2

• Taper gradually when discontinuing to avoid withdrawal symptoms 1

Critical Monitoring and Side Effects

• Monitor for suicidal thinking and behavior, especially in the first months and after dose changes, with a pooled risk of 1% versus 0.2% placebo (NNH = 143) 4

• Common early side effects include nausea, headache, insomnia, nervousness, and initial anxiety/agitation, which most often resolve with continued treatment 4

• Sexual dysfunction may persist as a long-term side effect 4

Pitfalls to Avoid

• Do not escalate doses too quickly—allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window 4

• Do not abandon treatment before 12 weeks, as full response requires patience due to the logarithmic response curve of SSRIs 4

• Do not discontinue abruptly—taper gradually to avoid withdrawal symptoms 4

• Avoid benzodiazepines for long-term management despite their rapid anxiolytic effects, as they carry risks of tolerance, dependence, and paradoxically may worsen long-term outcomes—one study found 63% of trauma patients on benzodiazepines developed PTSD versus only 23% on placebo 4

Supporting Evidence from Guidelines

• The World Federation of Societies of Biological Psychiatry (WFSBP) identifies SSRIs and the SNRI venlafaxine as first-line treatments for PTSD, with CBT as the psychotherapy modality with the best body of evidence 5

• Multiple systematic reviews and meta-analyses support SSRIs and SNRIs as first-line agents for most anxiety disorders, particularly given frequent comorbidity with mood disorders 6, 7