Prazosin is the First-Line Drug of Choice for Treating Nightmares in PTSD
Prazosin is the recommended first-line pharmacological treatment for nightmares, particularly those associated with PTSD, due to its demonstrated efficacy and favorable side effect profile. 1
Mechanism and Efficacy
Prazosin is an alpha-1 adrenergic receptor antagonist that reduces CNS sympathetic outflow throughout the brain. It specifically targets the elevated noradrenergic activity that contributes to disruption of normal REM sleep in PTSD patients 1.
Multiple studies demonstrate prazosin's effectiveness:
- Significantly reduces nightmare frequency compared to placebo 1
- Decreases CAPS nightmare scores by 3.1 ± 0.3 vs 1.2 ± 0.3 for placebo 1
- Improves sleep quality measures (PSQI scores) 1
- Shows rapid response, often within 1-2 weeks 2
Dosing Algorithm
- Initial dose: Start at 1 mg at bedtime
- Titration: Increase by 1-2 mg every 3-7 days
- Target dose:
- Civilian patients: Average 3 mg (range 1-10 mg)
- Military veterans: Higher doses (9.5-15.6 mg/day)
- Women may respond to lower doses than men (7.0 mg vs 15.6 mg) 3
- Maximum dose: Up to 20 mg at bedtime and 5 mg midmorning 4
Monitoring
- Check blood pressure after first dose and with each significant dose increase
- Monitor for orthostatic hypotension, especially during initiation
- Track nightmare frequency and intensity using standardized measures (CAPS or sleep diaries)
Important Considerations
- First-dose effect: Initial dose should be taken at bedtime to minimize risk of syncope
- Drug interactions: Use caution with PDE-5 inhibitors due to additive hypotensive effects 3
- Concomitant medications: SSRIs may decrease prazosin efficacy for PTSD treatment 1, 3
- Common side effects: Dizziness, drowsiness, headache, orthostatic hypotension 1
Second-Line Options (When Prazosin Is Ineffective or Contraindicated)
Topiramate
- Most effective medication to add to prazosin for inadequate response 3
- Start at 12.5-25 mg daily, increase by 25-50 mg every 3-4 days
- Most responders require ≤100 mg/day 3
- Reduces nightmare frequency from 3.97 to 2.07 nights/week 3
Clonidine
- Alpha-2 adrenergic receptor agonist with similar mechanism to prazosin
- Dosage: 0.2-0.6 mg in divided doses 1
- Long history of use in traumatized refugees 1
- Monitor for hypotension
Other Options (Limited Evidence)
- Atypical antipsychotics: Risperidone, olanzapine, aripiprazole 1, 3
- Trazodone: Effective but with significant side effects including priapism 1
- Benzodiazepines: Triazolam and nitrazepam may be considered 1
- Not recommended: Clonazepam and venlafaxine have been shown to be ineffective 1
Non-Pharmacological Approaches
Image Rehearsal Therapy (IRT) should be considered as an addition to pharmacological treatment, particularly for patients with partial response to medication 1, 3.
Special Populations
Prazosin has shown efficacy in both combat and non-combat related PTSD, as well as in patients with serious medical illness experiencing nightmares without PTSD diagnosis 5.
Prazosin remains the most well-studied and effective medication for PTSD-related nightmares, with a relatively rapid onset of action and favorable risk-benefit profile compared to alternatives.