What is the recommended starting dose and titration schedule of prazosin for hypertension, PTSD-related nightmares, and benign prostatic hyperplasia, including adjustments for elderly patients?

Prazosin Dosing Across Indications

Hypertension

Start prazosin at 0.5–1 mg at bedtime to minimize first-dose hypotension, then titrate to 1 mg three times daily over the first 4 days, with further increases up to 20–30 mg/day in divided doses as needed for blood pressure control. 1, 2

• Initial dosing protocol for hypertension: Give 0.5 mg on day 1, then 0.5 mg three times daily on days 2–4, followed by 1 mg three times daily thereafter 2
• Titrate gradually up to a maximum of 30 mg/day in divided doses for resistant hypertension 2
• The bedtime-only initial dose strategy reduces syncope risk to 0.15% (1 in 667 patients) 1
• Withhold diuretics for 1 day before starting prazosin to further reduce first-dose hypotension 1
• Monitor for orthostatic hypotension after the first dose and with each significant increase 1, 2

Special Populations in Hypertension

• Prazosin is particularly useful in patients with renal impairment, diabetes, hyperlipidemia, or bronchospasm 1
• Fluid retention may develop with long-term use, requiring addition of a diuretic 1

---

PTSD-Related Nightmares

For PTSD nightmares, start prazosin at 1 mg at bedtime and increase by 1–2 mg every few days until nightmares improve, targeting 3–4 mg/day in civilians or 9.5–15.6 mg/day in military veterans, with most patients responding below 10–20 mg/day. 3, 4

Civilian Populations

• Average effective dose is 3.1 ± 1.3 mg/day (range 3–4 mg) 3
• Controlled trials have evaluated doses up to 10 mg/day in civilian PTSD 3
• Initiate at 1 mg at bedtime, then increase by 1–2 mg every few days based on nightmare frequency 3, 4

Military Veterans and Combat-Related PTSD

• Veterans require substantially higher doses: mean effective range 9.5–15.6 mg/day 3
• Active-duty men require mean doses of 15.6 ± 6.0 mg/day, while women require 7.0 ± 3.5 mg/day 3
• Studies in military populations have used 10–16 mg at night 4
• Divided dosing may be considered for severe cases in military personnel 3

Dosing Algorithm for PTSD Nightmares

1. Start 1 mg at bedtime (single dose) 3, 4
2. Increase by 1–2 mg every few days based on response 3
3. Target 3–4 mg/day for civilians or 9.5–15.6 mg/day for veterans 3
4. Maximum recommended: 10–20 mg/day for most patients 3
5. Monitor blood pressure with each dose increase 3
6. Track nightmare frequency using CAPS distressing-dreams score (target ≥4/8 for treatment indication) 5

Critical Drug Interactions

• SSRIs/SNRIs significantly attenuate prazosin efficacy: CAPS score improvement drops from 30.1 points to only 9.6 points when SSRIs are co-administered 5
• In the 2018 VA trial showing no benefit, 78% of participants were on maintenance antidepressants 5
• Consider this interaction when deciding whether to prescribe prazosin in patients already on antidepressants 5

Evidence Nuances

• The American Academy of Sleep Medicine maintains prazosin as "first choice for pharmacologic therapy" despite a large 2018 VA trial (304 veterans, 26 weeks) showing no benefit over placebo 5, 6
• Early positive RCTs in civilians and veterans demonstrated significant reductions in nightmare frequency 5
• The recommendation was downgraded but not withdrawn because "many patients respond very well" 5, 6
• Prazosin is not curative: nightmares return to baseline when discontinued 3, 6

---

Benign Prostatic Hyperplasia (BPH)

For BPH, initiate prazosin at 1 mg twice daily and titrate to typical maintenance doses of 2–6 mg/day in divided doses, monitoring for orthostatic hypotension. 4, 7

• Start at 1 mg twice daily rather than the bedtime-only dosing used for PTSD 4
• Maintenance range is typically 2–6 mg/day in divided doses 4
• Monitor for orthostatic hypotension, especially early in therapy 7

---

Elderly Patients and High-Risk Populations

Use lower initial doses in elderly patients, those on concurrent antihypertensives, or patients with recent stroke, as first-dose hypotension can be severe even at 0.5 mg. 3, 8

• The American Academy of Sleep Medicine recommends lower initial doses in elderly or those on antihypertensives 3
• Caution in recent stroke: Three cases of hemorrhagic stroke patients developed severe hypotension with consciousness disturbance even at 0.5 mg 8
• Consider starting at 0.5 mg or lower in high-risk elderly patients 8

---

Monitoring and Safety

• First-dose phenomenon: Monitor blood pressure and orthostatic vitals after initial dose 3, 1, 7
• Dizziness and lightheadedness are common but usually transient 3
• Orthostatic hypotension typically resolves during continued treatment 3
• Sexual dysfunction is uncommon compared to other antihypertensives 1
• Prazosin is well-tolerated even at doses up to 20 mg/day 3

---

Common Pitfalls

• Don't use prazosin as a general anxiolytic—it only works for trauma-related nightmares, not generalized anxiety 5
• Don't expect sustained benefit if SSRIs are co-prescribed—the interaction is substantial 5
• Don't assume civilian dosing applies to veterans—military populations need 3–5 times higher doses 3
• Don't forget to withhold diuretics for 1 day before starting in hypertensive patients 1
• Don't overlook stroke history—even 0.5 mg can cause severe hypotension in recent hemorrhagic stroke 8