What is the preferred medication between trazosin (trazodone) and prazosin for treating post-traumatic stress disorder (PTSD)-related nightmares?

Prazosin vs Trazodone for PTSD-Related Nightmares

Prazosin is the preferred medication for treating PTSD-related nightmares with Level A evidence from the American Academy of Sleep Medicine, while trazodone has more limited supporting evidence. 1

First-Line Treatment Approach

Non-Pharmacological Options

• Image Rehearsal Therapy (IRT) should be attempted first before medication
• If IRT is insufficient after 4-6 weeks, pharmacological treatment should be added

Pharmacological Treatment

Prazosin (First-Line)

• Dosing protocol:

  • Start at 1 mg at bedtime
  • Titrate by 1-2 mg every 3-7 days
  • Target effective dose: 3 mg (range 1-10+ mg)
  • Some patients may require higher doses (up to 30-45 mg in treatment-resistant cases)
  • Consider twice-daily dosing for some patients 1

• Efficacy:

  • Level A evidence (highest recommendation) from American Academy of Sleep Medicine 1
  • Reduces nightmare frequency by over 50% compared to 15% with placebo 2
  • Therapeutic benefit can occur with doses as low as 1 mg daily 3
  • Suppression of nightmare symptoms may occur within one week of initiation 3

• Monitoring:

  • Watch for orthostatic hypotension, especially after first dose
  • Monitor blood pressure during treatment 1

Trazodone (Alternative Option)

• Dosing:

  • Effective dose range: 50-200 mg nightly (for 70% of patients)
  • Mean effective dose: 212 mg/day 2, 4

• Efficacy:

  • Decreased nightmare frequency from 3.3 to 1.3 nights/week in 72% of patients 4
  • Helps with sleep onset (92% of patients) and sleep maintenance (78% of patients) 4
  • Lower level of evidence compared to prazosin 1

• Side effects:

  • 60% of patients experience side effects, particularly daytime sedation or dizziness
  • 12% reported priapism in one study (higher than expected) 4
  • Other side effects include dry mouth/sinuses, muscle pain, and agitation 2

Clinical Decision Algorithm

1. Start with non-pharmacological treatment (IRT)
2. If IRT is insufficient after 4-6 weeks, add pharmacological treatment:
   • First choice: Prazosin (start at 1 mg, titrate as needed)
   • If prazosin is contraindicated or not tolerated: Consider trazodone
3. If combined approach fails:
   • Consider clonidine (0.1-0.6 mg) or atypical antipsychotics as adjunctive therapy 1

Important Considerations and Pitfalls

• Avoid underdosing prazosin - many patients require doses higher than initially prescribed
• Monitor for orthostatic hypotension with prazosin, especially after first dose
• Be vigilant about priapism with trazodone - directly ask male patients about this side effect
• Avoid medications specifically not recommended for nightmare disorder:
  • Clonazepam (ineffective)
  • Venlafaxine (not recommended) 1
• Don't rely solely on pharmacological treatment - combination with behavioral approaches is optimal
• Don't discontinue treatment prematurely - continued therapy may be necessary for sustained benefit

Prazosin demonstrates superior efficacy and safety profile compared to trazodone for PTSD-related nightmares, with stronger evidence supporting its use as first-line pharmacological treatment when medication is needed 1, 5.