What are the recommended starting dose, titration schedule, and safety considerations for prazosin in adults for hypertension, benign prostatic hyperplasia, and post‑traumatic stress disorder‑related nightmares?

Prazosin Dosing and Safety Across Indications

Starting Dose and Titration

Start prazosin at 1 mg at bedtime regardless of indication to minimize first-dose orthostatic hypotension, then increase by 1–2 mg every few days until clinical response is achieved. 1, 2

Hypertension

• Initial dose: 1 mg 2–3 times daily
• Maintenance range: typically 6–15 mg/day divided in 2–3 doses
• Monitor blood pressure after initial dose and with each increase 2

Benign Prostatic Hyperplasia (BPH)

• Initial dose: 1 mg at bedtime
• Titrate gradually to 1–9 mg/day based on symptom relief 3
• 60–70% of patients experience significant improvement in obstructive and irritative symptoms, improved flow rates, and decreased urethral pressure 3
• Alpha-1 blockade relaxes smooth muscle contractions in the enlarged prostate 3

PTSD-Related Nightmares

• Initial dose: 1 mg at bedtime 1, 2
• Civilians typically require 3–4 mg/day for adequate response 1, 2
• Military veterans often need substantially higher doses of 9.5–15.6 mg/day 1, 2
• For severe symptoms in military personnel, divided dosing (bedtime plus mid-morning) has been used successfully 4
• Titrate by 1–2 mg every few days until nightmares are controlled 1, 2

Eligibility Criteria for PTSD Nightmare Treatment

Only prescribe prazosin for PTSD nightmares when patients have persistent, frequent nightmares (≥ several times per week) that persist despite adequate trauma-focused psychotherapy and cause marked sleep disruption and functional impairment. 1

• A CAPS distressing-dreams score ≥ 4/8 defines a recurrent, distressing PTSD-associated nightmare that qualifies for prazosin therapy 1
• Track nightmare frequency and distress with standardized instruments such as the CAPS distressing-dreams item and sleep diary to evaluate treatment response 1

Critical Safety Considerations

Orthostatic Hypotension

• The most important safety concern is first-dose orthostatic hypotension, which is why the 1 mg starting dose is mandatory 1, 2, 5
• Monitor blood pressure after initial dose and with each significant dose increase 2, 4
• Elderly patients and those on concurrent antihypertensives are at highest risk 5

Drug Interactions That Reduce Efficacy

Concurrent SSRIs or SNRIs may significantly attenuate prazosin's efficacy for PTSD nightmares—a critical interaction that clinicians often miss. 1

• In a 2013 military trial, patients on SSRIs had much smaller CAPS score reductions (mean decrease ≈ 9.6) versus those not on SSRIs (mean decrease ≈ 30.1) 1
• In the 2018 VA trial where 78% of participants were on maintenance antidepressants, prazosin showed no benefit over placebo 1
• Consider this interaction when planning treatment; you may need to choose between optimizing antidepressant therapy versus prazosin efficacy 1

Evidence Quality and Guideline Strength

Mixed Evidence Base

• Early randomized trials in both civilian and veteran populations demonstrated significant reductions in nightmare frequency and improvements in sleep quality 1
• However, a large 2018 VA randomized controlled trial (304 participants, 26-week follow-up) found no statistically significant difference between prazosin and placebo on nightmare frequency, sleep quality, or other PTSD outcomes 1
• Despite this negative trial, the American Academy of Sleep Medicine affirmed that "many patients respond very well to prazosin and this agent remains the first choice for pharmacologic therapy," though the recommendation was downgraded to conditional 1, 2

Practical Implications

• The American Academy of Sleep Medicine maintains a Level A recommendation for prazosin in PTSD-related nightmares despite mixed evidence 2
• Individual patient response varies widely; some patients experience complete elimination of trauma nightmares and resumption of normal dreaming, while others have minimal or no response 6

Common Pitfalls to Avoid

Do not use prazosin as a general anxiolytic—it targets nightmare-related sleep disruption, not daytime anxiety symptoms. 2

• Prazosin may reduce anxiety symptoms only if they stem from trauma-related nightmares causing sleep deprivation that exacerbates daytime anxiety 2
• The American Academy of Sleep Medicine frames prazosin as treatment for nightmare disorder with secondary benefits on PTSD symptoms, not as primary anxiolytic therapy 2

Nightmares return to baseline intensity when prazosin is discontinued—this is not a curative treatment. 2, 4

• Patients should be informed about the possibility of diminishing effectiveness before starting treatment 4
• Some patients experience initial improvement that becomes minor, short-lived, or reaches an unsatisfactory plateau 4

Alternative Agent When Prazosin Fails or Causes Panic

If prazosin induces panic attacks or proves ineffective, switch to topiramate as the next-line agent for trauma-related nightmares. 1

• Initiate topiramate at 12.5–25 mg daily and titrate by 25–50 mg increments every 3–4 days 1
• 91% of patients who achieved full therapeutic response did so with ≤100 mg/day 1
• Topiramate reduced nightmare frequency in 79% of treated individuals, with complete suppression in 50% 1
• Monitor for cognitive slowing, peripheral tingling, and rare acute angle-closure glaucoma 1
• Topiramate works via GABA-A receptor stimulation and glutamate inhibition, avoiding the alpha-1 blockade that can precipitate panic 1