prazosin

General Information

Prazosin is an alpha-1 adrenergic antagonist approved for hypertension and commonly used off label to reduce PTSD-related nightmares and sleep disruption.

Evidence is mixed across populations and trials, so treat it as a symptom-targeted adjunct with explicit reassessment milestones rather than an indefinite prescription.

Prazosin is most useful when nightmares are a prominent driver of sleep disruption and baseline blood pressure can tolerate an alpha-1 blocker; document baseline vitals, define success metrics (nightmare frequency, sleep continuity), and stop rather than continuing indefinitely if benefit is unclear.

The prazosin compare view, prazosin evidence feed, and prazosin print page can support aligning sleep symptom goals with safety planning.

Key early risks are first-dose syncope and orthostatic hypotension; start low at bedtime and titrate slowly, especially when combined with other blood-pressure-lowering medications. Because evidence is mixed, build in a reassessment milestone (for example after titration to a tolerated target dose) and taper off if nightmares do not clearly improve.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Selective alpha-1 adrenergic receptor antagonism reduces sympathetic tone and peripheral vascular resistance.

Central noradrenergic modulation is the proposed mechanism for nightmare reduction in PTSD.

Alpha-1 blockade can reduce trauma-related adrenergic arousal at night, but clinical response is variable; pair with trauma-focused therapy and sleep interventions rather than using prazosin as a standalone PTSD strategy.

• Alpha-1 antagonism (vasodilation; orthostatic hypotension risk).

Metabolism and Pharmacokinetics

• Peak plasma concentrations occur at ~3 hours after oral administration (label).
• Plasma half-life is ~2–3 hours (label).
• Extensively metabolized; excreted mainly via bile and feces (label).
• Despite a short plasma half-life, hypotension and dizziness can persist, especially early in titration or when combined with other blood-pressure-lowering agents.

Dosing and Administration

• PTSD nightmares (off label): start 1 mg at bedtime; titrate gradually (often in 1 mg increments) based on nightmare frequency and tolerability.
• If doses are missed for several days, consider restarting at a low dose and retitrating to reduce first-dose syncope risk.
• Do not “catch up” missed doses; prioritize safety, retitrate as needed, and reassess alternative nightmare/sleep strategies if titration is limited by hypotension.
• Daytime dosing may be used for hyperarousal symptoms, but increases hypotension risk and requires close monitoring.
• If daytime dosing is used, start even lower and monitor standing blood pressure and falls risk; many patients tolerate bedtime-only dosing more safely.

Monitoring & Labs

• Check blood pressure (including orthostatic vitals) during initiation and after dose increases; counsel hydration and slow positional changes.
• Reassess falls risk and co-prescribed sedatives/antihypertensives; adjust titration speed accordingly.
• Define a reassessment milestone for nightmare response; taper and stop if benefit is unclear after an adequate trial.
• If doses are missed for several days, restart low and retitrate to reduce first-dose syncope risk.

Sources: FDA/DailyMed label; meta-analyses and guideline reviews.

Adverse Effects

Interactions

• Additive hypotension with other antihypertensives, nitrates, or PDE5 inhibitors (sildenafil/tadalafil).
• Antipsychotics with orthostatic liability (clozapine, quetiapine) can compound dizziness and falls.
• Alcohol, sedatives, and dehydration can compound dizziness and syncope; provide harm-reduction counseling and reassess during intercurrent illness.

Other Useful Information

• Define the target symptom and document a titration and reassessment plan.
• Pair with PTSD-first-line treatments and sleep interventions; avoid treating prazosin as a standalone PTSD strategy.
• If the response is unclear after a reasonable titration window, taper and discontinue rather than continuing indefinitely.
• Track nightmares and sleep quality with brief check-ins (sleep diary or weekly rating); if there is clear benefit, periodically reassess whether the dose can be reduced while maintaining symptom control.

References

1. Prazosin hydrochloride prescribing information — DailyMed (2025)
2. Trial OF Prazosin FOR Post Traumatic Stress Disorder IN Military Veterans — The New England Journal of Medicine (2018)
3. Prazosin FOR Treatment OF Post Traumatic Stress Disorder — CNS Spectrums (2021)
4. Treatment Guidelines for PTSD — Journal of Clinical Medicine (2021)