Prazosin Dosing for PTSD-Associated Nightmares
Start prazosin at 1 mg at bedtime and titrate by 1-2 mg every few days until nightmares resolve, targeting 3-4 mg/day for civilians and 10-16 mg/day for military veterans, with women generally requiring lower doses than men. 1
Initial Dosing Strategy
- Begin with 1 mg at bedtime to minimize first-dose orthostatic hypotension, which is the most common side effect 1, 2
- Monitor blood pressure after the first dose and with each significant dose increase 2
- Increase by 1-2 mg every few days based on nightmare response 1, 2
- Lower initial doses should be used in elderly patients or those on concurrent antihypertensive medications 2
Target Dose Ranges by Population
The effective dose varies dramatically based on the patient population, which is a critical consideration:
Civilian Trauma Victims
- Target dose: 3-4 mg/day (mean effective dose 3.1 ± 1.3 mg) 1, 2
- This lower dose range is typically sufficient for non-military PTSD patients 1
Military Veterans
- Target dose: 9.5-15.6 mg/day (range can extend to 20 mg) 1
- One study showed mean doses of 13 ± 3 mg/day for veterans with treatment-resistant nightmares 1
- Higher doses are consistently needed in combat-related PTSD 3, 4
Gender-Specific Dosing in Active-Duty Military
- Men: 15.6 ± 6.0 mg at bedtime 1, 2
- Women: 7.0 ± 3.5 mg at bedtime 1, 2
- This represents a clinically significant sex difference that should guide titration 1
Administration Schedule
- Single bedtime dose is the standard approach for most patients 2, 5
- For severe cases in military personnel, divided dosing (bedtime plus mid-morning dose) may be considered 1
- One study used bedtime dosing with a repeated mid-morning dose, both titrated based on response 1
Critical Monitoring and Adjustments
What to Monitor
- Assess nightmare frequency and intensity using standardized measures when possible (CAPS distressing dreams item is the gold standard) 1, 2
- Monitor for orthostatic hypotension, particularly dizziness and lightheadedness 1, 2
- Most orthostatic symptoms are transient and resolve during continued treatment 1, 5
Important Drug Interaction
- Concurrent SSRI use may significantly diminish prazosin response 1, 2, 5
- In one study, patients not taking SSRIs had CAPS score reductions of 30.1 ± 3.8 versus only 9.6 ± 6.8 in those on SSRIs 1
- Consider this interaction when titrating dose or evaluating treatment failure 1
Common Pitfalls to Avoid
Underdosing military veterans: The most common error is stopping at civilian doses (3-4 mg) when treating combat veterans who typically require 10-16 mg 1, 3
Expecting sustained benefit after discontinuation: Nightmares frequently return to baseline intensity when prazosin is stopped, so this is maintenance therapy, not curative 1, 5
Using as a general anxiolytic: Prazosin is specifically for trauma-related nightmares, not general anxiety—it won't work for non-trauma anxiety 5
Ignoring the SSRI interaction: If a patient on an SSRI isn't responding, the issue may be the drug interaction rather than prazosin inefficacy 1, 2
Evidence Quality Considerations
While the American Academy of Sleep Medicine previously gave prazosin a Level A recommendation for PTSD-associated nightmares 1, this was downgraded based on a large 2018 VA study of 304 participants showing no benefit at mean doses of 14.8 ± 6.1 mg over 26 weeks 1. Notably, 78% of participants in this negative study were on maintenance antidepressants, which may explain the lack of response 1.
Despite this contradictory evidence, prazosin remains the first-choice pharmacologic therapy because many patients respond very well in clinical practice, and the medication interaction with antidepressants likely explains the negative trial 1. The Task Force acknowledged that clinicians clearly observe robust responses in many patients 1.