When do we use clonidine (antihypertensive medication) versus prazosin (alpha-blocker) for treating nightmares, particularly in patients with Post-Traumatic Stress Disorder (PTSD)?

Pharmacotherapy for Nightmares in PTSD

Prazosin is the first-line medication for PTSD-associated nightmares with Level A evidence, while clonidine may be considered as a second-line option with Level C evidence when prazosin is not tolerated or effective. 1

First-Line Treatment: Prazosin

• Prazosin, an alpha-1 adrenergic antagonist, is recommended as first-line therapy for PTSD-associated nightmares based on multiple placebo-controlled trials 2, 1
• The mechanism involves reducing elevated CNS noradrenergic activity that contributes to disruption of normal REM sleep and arousal symptoms including nightmares 2, 1
• Multiple Level 1 studies with military veterans and civilian trauma victims demonstrated significant reduction in trauma-related nightmares 2, 3

Dosing Protocol for Prazosin:

• Start at 1 mg at bedtime and increase by 1-2 mg every few days until effective 2
• Average effective dose is approximately 3 mg, though doses up to 13.3 mg/day have been used in military veterans 2, 4
• Treatment duration in studies ranged from 3-9 weeks with maintained improvement 2
• Monitor for orthostatic hypotension, the main side effect of concern 2, 5

Second-Line Treatment: Clonidine

• Clonidine may be considered for PTSD-associated nightmares with Level C evidence when prazosin is not effective or tolerated 2
• Clonidine is an α2-adrenergic receptor agonist that suppresses sympathetic nervous system outflow throughout the brain 2
• Despite being used for over 20 years in treating PTSD in refugee populations, it lacks the rigorous clinical trial evidence that prazosin has 2

Dosing Protocol for Clonidine:

• Typical dosing range is 0.2-0.6 mg in divided doses 2, 6
• Low-dose clonidine increases REM sleep while medium-dose decreases REM sleep 2
• Monitor for potential blood pressure reduction, especially when increasing doses 2
• Case reports show effectiveness in treating nightmares in veterans with co-morbid PTSD and traumatic brain injury 6

When to Choose Which Medication

• Choose prazosin as first-line treatment for most patients with PTSD-associated nightmares due to stronger evidence base 1, 3
• Consider clonidine when:
  • Patient has experienced intolerable side effects with prazosin 2
  • Patient has inadequate response to prazosin despite appropriate dose titration 2
  • Patient has comorbid conditions that might benefit from clonidine's broader effects (e.g., opioid withdrawal, hypertension) 2
  • Patient has a history of positive response to clonidine for other indications 6

Other Treatment Considerations

• Both medications should be used as adjuncts to ongoing psychotherapy and other psychotropic medications 2
• Other medications with limited evidence (Level C) that may be considered when both prazosin and clonidine fail include trazodone, atypical antipsychotics, and topiramate 2, 1
• Avoid clonazepam and venlafaxine, as evidence shows they are ineffective for PTSD-associated nightmares 1
• Trazodone has shown some efficacy but has significant side effects including daytime sedation, dizziness, headache, and priapism 2

Monitoring and Follow-up

• Monitor blood pressure with both medications, particularly after initial dose and with dose increases 2
• Assess nightmare frequency and intensity before treatment and at regular intervals 3, 4
• Evaluate daytime functioning, as successful treatment should improve sleep quality and reduce daytime fatigue 1
• Consider prazosin's more rapid onset of action (within days to weeks) compared to many other psychotropic medications 5