What is the recommended dose of prazosin (Prazosin) for treating anxiety, particularly in post-traumatic stress disorder (PTSD)?

Prazosin Dosing for Anxiety in PTSD

For PTSD-related nightmares and anxiety symptoms, start prazosin at 1 mg at bedtime and titrate by 1-2 mg every few days until clinical response is achieved, with target doses of 3-4 mg/day for civilians and 9.5-15.6 mg/day for military veterans. 1

Initial Dosing Strategy

• Begin with 1 mg at bedtime to minimize first-dose hypotension risk 2, 1
• Increase by 1-2 mg every few days based on nightmare response and tolerability 2, 1
• Monitor blood pressure after the initial dose and with each significant dose increase 1, 3
• Use lower starting doses in elderly patients or those on concurrent antihypertensive medications 1

Target Dose Ranges by Population

Civilian PTSD patients:

• Average effective dose is 3-4 mg/day (mean 3.1 ± 1.3 mg) 2, 1
• Doses as low as 1 mg daily can provide therapeutic benefit 4
• Effective range documented from 1-15 mg 2

Military veterans with combat-related PTSD:

• Require substantially higher doses: 9.5-15.6 mg/day on average 2, 1
• One study showed mean doses of 13 ± 3 mg/day for treatment-resistant nightmares 2
• Maximum doses up to 20 mg have been studied in large trials 2

Gender-specific dosing for active-duty military:

• Men: mean effective dose 15.6 ± 6.0 mg 2, 1
• Women: mean effective dose 7.0 ± 3.5 mg 2, 1

Administration Schedule

• Single bedtime dose is the standard initial approach for nightmare management 1
• For severe cases, particularly in military personnel, divided dosing (bedtime plus mid-morning) may be considered 2
• Clinical response typically occurs within one week of initiation 4

Important Clinical Considerations

Drug interactions:

• Patients taking SSRIs may have diminished response to prazosin for PTSD symptoms 2, 1, 3
• In one study, CAPS scores decreased by 30.1 ± 3.8 in non-SSRI users versus only 9.6 ± 6.8 in SSRI users 2
• Consider this interaction when planning treatment, though do not necessarily discontinue effective antidepressant therapy

Monitoring parameters:

• Assess nightmare frequency and intensity using standardized measures (CAPS distressing dreams item, PSQI) when possible 1
• Watch for orthostatic hypotension, particularly after initial doses 2
• Dizziness and lightheadedness are common but usually transient 2, 1

Discontinuation effects:

• Nightmares frequently return to baseline intensity when prazosin is stopped 2, 1, 3
• This suggests ongoing treatment is necessary for sustained benefit

Evidence Quality and Caveats

The American Academy of Sleep Medicine downgraded their recommendation for prazosin after a large 2018 VA study of 304 patients showed no benefit at mean doses of 14.8 mg over 26 weeks 2. However, this contradictory finding occurred in a population where 78% were on concurrent antidepressants, which may explain the negative result 2.

Despite this, prazosin remains the first-choice pharmacologic agent because multiple prior RCTs demonstrated clear efficacy, and clinicians consistently observe robust responses in many patients 2. The mechanism—blocking alpha-1 adrenergic receptors to reduce elevated CNS noradrenergic activity—directly targets the pathophysiology of PTSD-related arousal symptoms 2, 3.

Practical Titration Algorithm

1. Start 1 mg at bedtime 1
2. Check blood pressure after first dose 1
3. If tolerated, increase to 2 mg after 3-5 days 2
4. Continue increasing by 1-2 mg every 3-5 days 2, 1
5. For civilians: target 3-4 mg and assess response 1
6. For military veterans: continue titrating to 10-16 mg as needed 2
7. If partial response at standard doses, consider higher doses (up to 20 mg has been studied) 2
8. Monitor for orthostatic symptoms throughout titration 2