Is it safe to start prazosin for PTSD flashbacks in a 57-year-old woman with inappropriate sinus tachycardia who is already taking metoprolol?

Safety of Adding Prazosin to Metoprolol in Inappropriate Sinus Tachycardia

Yes, it is safe to initiate prazosin for PTSD flashbacks in this patient already taking metoprolol for inappropriate sinus tachycardia, but you must start with 1 mg at bedtime and monitor closely for additive hypotensive effects, particularly orthostatic hypotension. 1

Key Safety Consideration: Additive Hypotension Risk

• The FDA label explicitly warns that hypotension may develop in patients given prazosin who are also receiving a beta-blocker such as propranolol (or metoprolol), though this is manageable with proper dosing and monitoring 1
• The primary concern is additive blood pressure lowering, not a pharmacodynamic interaction that worsens tachycardia or creates dangerous arrhythmias 1
• Syncope occurs in approximately 1% of patients when prazosin is initiated at doses ≥2 mg, but this risk is minimized by starting at 1 mg and titrating slowly 1

Mandatory Dosing Protocol to Minimize Risk

• Always start prazosin at 1 mg at bedtime—the 2 mg and 5 mg capsules are contraindicated for initial therapy per FDA labeling 1
• Titrate slowly over weeks, increasing by 1 mg increments as tolerated, with careful blood pressure monitoring before each dose escalation 1
• For daytime flashbacks, prazosin can be dosed 2-3 times daily after the patient tolerates nighttime dosing, given its 2-3 hour half-life 2

Clinical Monitoring Strategy

• Check orthostatic vital signs before each dose increase: measure blood pressure supine and after 1-3 minutes of standing 1
• Counsel the patient to avoid situations where injury could result if syncope occurs during the first 30-90 minutes after each new dose 1
• If syncope occurs, place the patient recumbent and treat supportively—this adverse effect is self-limiting and typically does not recur after initial titration 1

Why This Combination Is Reasonable

• Metoprolol is already first-line therapy for inappropriate sinus tachycardia and should remain in place for rate control 3, 4
• Prazosin does not worsen tachycardia—in fact, the FDA label notes that syncopal episodes are occasionally preceded by severe tachycardia (120-160 bpm), but this is a reflex response to hypotension, not a direct drug effect 1
• Prazosin is effective for PTSD-related flashbacks when dosed during the day, with therapeutic benefit occurring at doses as low as 1 mg daily and symptom suppression within one week 2, 5, 6

Specific Pitfalls to Avoid

• Do not start prazosin at 2 mg or higher—this dramatically increases syncope risk, especially when combined with a beta-blocker 1
• Do not add prazosin if the patient has uncontrolled hypotension or symptomatic orthostatic hypotension on metoprolol alone—optimize beta-blocker dosing first 1
• Warn the patient about dizziness and lightheadedness, which are more common than syncope and represent the expected blood pressure-lowering effect 1

Evidence for Prazosin in PTSD

• Multiple randomized controlled trials, open-label studies, and retrospective reviews demonstrate that prazosin significantly decreases trauma nightmares, avoidance, hypervigilance, and improves overall PTSD symptoms 6
• Prazosin is well-tolerated, with orthostatic hypotension being the most frequently reported adverse event—no significant difference in blood pressure was observed at the end of trials when properly titrated 6
• The mechanism involves central alpha-1 adrenergic blockade, reducing autonomic arousal caused by PTSD, making it particularly effective for intrusive symptoms like flashbacks 2, 5

Inappropriate Sinus Tachycardia Context

• Beta-blockers remain the cornerstone of IST management, and metoprolol should be continued at the current dose unless the patient develops intolerable side effects 3, 4
• IST treatment is symptom-driven, and the risk of tachycardia-induced cardiomyopathy in untreated patients is likely small, so the focus should be on quality of life—addressing PTSD flashbacks is entirely appropriate 3
• Ensure the diagnosis of IST is confirmed (persistent resting HR >100 bpm with excessive rate increase to activity and nocturnal normalization on 24-hour Holter) to distinguish it from POTS, which would require different management 3, 7