What medications are recommended for the treatment of Post-Traumatic Stress Disorder (PTSD)?

Medications for Post-Traumatic Stress Disorder (PTSD)

Selective Serotonin Reuptake Inhibitors (SSRIs), specifically sertraline and paroxetine, are the first-line pharmacological treatments for PTSD as they have FDA approval and strong evidence supporting their efficacy. 1, 2

First-Line Medications

SSRIs

• Sertraline (Zoloft)

  • FDA-approved for PTSD 1, 2
  • Dosing: Start at 25-50 mg daily, titrate to 50-200 mg daily (mean effective dose ~150 mg) 2
  • Efficacy: 60% response rate vs 38% for placebo 3
  • Maintenance: Continued treatment for 24-28 weeks after response significantly reduces relapse rates 2, 4
  • Side effects: Insomnia (35%), diarrhea (28%), nausea (23%), fatigue (13%), decreased appetite (12%) 3

• Paroxetine

  • FDA-approved for PTSD 1
  • Demonstrated efficacy in controlled trials 1

• Fluoxetine

  • Effective in controlled trials but not FDA-approved specifically for PTSD 1, 5

Second-Line Medications

Alpha-1 Adrenergic Antagonists

• Prazosin
  • Strongly recommended for PTSD-associated nightmares (Level A evidence) 1
  • Dosing: Start at 1 mg at bedtime, increase by 1-2 mg every few days until effective
  • Average dose: 3 mg (range 1-10 mg), higher doses (9.5-13.3 mg) may be needed for severe cases 1
  • Mechanism: Reduces elevated CNS noradrenergic activity that contributes to PTSD symptoms 1
  • Monitor for: Orthostatic hypotension 1

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

• Venlafaxine
  • Consider as second-line treatment 6, 5
  • Starting dose: 37.5 mg daily; target dose: 225 mg daily 6
  • Monitor blood pressure due to potential for hypertension 6

Third-Line and Adjunctive Medications

Other Agents for PTSD-Associated Nightmares

• Clonidine (Level C evidence)

  • Alpha-2 adrenergic agonist that suppresses sympathetic outflow
  • Dosing: 0.2-0.6 mg in divided doses 1
  • Monitor for: Hypotension 1

• Trazodone

  • May reduce nightmare frequency (from 3.3 to 1.3 nights/week) 1
  • Dosing: 25-600 mg (mean 212 mg) 1
  • Side effects: Sedation, dizziness, headache, priapism, orthostatic hypotension 1

• Atypical antipsychotics (olanzapine, risperidone, aripiprazole)

  • Consider for PTSD with prominent paranoia or flashbacks 1, 5
  • Can be used as augmentation to SSRIs in refractory cases 5

• Topiramate

  • May reduce nightmare frequency and intensity 1
  • Dosing: Start at 25 mg daily, titrate to effect (typically 100-150 mg/day) 1
  • Side effects: Urticaria, nausea, glaucoma, headaches, cognitive effects 1

Medications to Use with Caution

• Tricyclic antidepressants and MAOIs

  • Consider as third-line options due to side effect profiles 5
  • Higher risk of cardiovascular complications and overdose toxicity 5

• Benzodiazepines

  • Not recommended for PTSD as they may worsen symptoms long-term 1, 5
  • Potential for dependence and possible worsening of PTSD 5

Treatment Algorithm

1. Initial Treatment:

   • Start with sertraline (25-50 mg/day) or paroxetine
   • Titrate dose every 1-2 weeks based on response and tolerability
   • Target dose for sertraline: 50-200 mg/day

2. Evaluate response after 8-12 weeks:

   • If good response: Continue for at least 12 months 2, 4
   • If partial response: Increase dose to maximum tolerated within therapeutic range

3. For inadequate response after 12 weeks of adequate dosing:

   • Switch to another SSRI or venlafaxine
   • Consider adding prazosin specifically for nightmares

4. For treatment-resistant PTSD:

   • Consider augmentation with atypical antipsychotics
   • Consider topiramate or other anticonvulsants, especially with comorbid bipolar disorder or prominent anger/impulsivity 5

Important Clinical Considerations

• Duration of treatment: Continue medication for at least 12-24 months after achieving remission to prevent relapse 2, 4
• Relapse rates: 26-52% of patients relapse when medication is discontinued versus 5-16% when maintained on medication 1
• Delayed response: Some patients (54%) who don't respond to acute treatment may respond with continued therapy beyond 12 weeks 4
• Predictors of delayed response: Higher baseline PTSD severity (CAPS-2 score >75) predicts longer time to response 4

Common Pitfalls to Avoid

1. Premature discontinuation: Maintain treatment for sufficient duration (12-24 months minimum after remission)
2. Inadequate dosing: Many patients require higher doses within the therapeutic range
3. Overlooking nightmares: Consider specific treatment for nightmares with prazosin if they persist despite SSRI therapy
4. Ignoring comorbidities: Adjust treatment approach for comorbid depression, substance use, or bipolar disorder
5. Benzodiazepine use: Avoid long-term use as they may worsen PTSD outcomes

Regular monitoring for side effects, suicidal ideation (especially in patients under 24), and treatment response using standardized measures is essential for optimal management.