A combat veteran with PTSD is started on a medication targeting hyperarousal symptoms and nightmares. Which agent has the best evidence for reducing trauma-related nightmares via alpha-1 adrenoreceptor blockade in the prefrontal cortex and amygdala?

• A Sertraline
• B Propranolol
• C Prazosin ✓
• D Clonidine

Explanation

Prazosin, a selective alpha-1 adrenoceptor antagonist, is the best-evidenced pharmacological agent for PTSD nightmares. During REM sleep, norepinephrine release in the amygdala and prefrontal cortex is believed to mediate trauma replay; prazosin blocks these alpha-1 receptors, reducing nightmare frequency and intensity. Multiple RCTs support its efficacy specifically for sleep disturbance and nightmares in PTSD. Sertraline and paroxetine are FDA-approved for overall PTSD (first-line), but neither targets nightmares specifically. Propranolol (beta-blocker) and clonidine (alpha-2 agonist) reduce peripheral adrenergic symptoms but have weaker evidence for nightmares.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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