Dr. Murray Raskind, Director of the VA Northwest Network Mental Illness Research Education and Clinical Center, has focused much of his career on PTSD and brain noradrenergic abnormalities. He has been extensively involved in studies related to prazosin and treatment of PTSD symptoms. Dr. Raskind will share his knowledge of prazosin's effects on PTSD. His presentation will review prazosin's effect on CNS noradrenergic activity and how it has affected PTSD in clinical situations.

This Q & A article will provide a glimpse into the session attendees will enjoy at the CPNP Annual Meeting. Register now to take advantage of this and more excellent programming planned for the 2013 Annual Meeting.

Why do you think it's important to treat PTSD-related sleep disturbances?

Sleep disturbance is more than a PTSD “related” problem. Rather, it is a central component of PTSD and the most common symptom for which Veterans and Service Members with combat operations-induced PTSD seek treatment. Distressed awakenings, with inability to return to sleep and often accompanied by trauma-related nightmares are particularly troublesome and likely exacerbate daytime hypervigilance, irritability/low anger threshold and avoidance symptoms. In addition to the benefits per se of successfully treating sleep disturbance, it is likely that psychotherapy for PTSD is substantially more successful after sleep has normalized, and alcohol misuse as “self medication” is reduced or eliminated. Keep in mind that prazosin is not sedating; it will not initiate sleep like a hypnotic. Rather it maintains sleep once achieved.

Do you agree with the Harvard South Shore Program that suggests treating nightmares before initiating an SSRI?

I do agree, and would broaden to treating both trauma nightmares (which are different from the common unpleasant and usually bizarre anxiety dream which is not responsive to prazosin) and distressed awakenings without recalled trauma nightmares before instituting an SSRI. In fact, I do not prescribe an SSRI or SNRI for combat-trauma PTSD (for which there is little evidence of efficacy for PTSD from available studies in U.S. Veterans) unless depressive symptoms are present (albeit sometimes difficult to distinguish from PTSD symptoms) or avoidance and irritability are prominent. Further, SSRIs can modestly disrupt sleep and intensify dreams.

What triggered your interest in the use of prazosin for the treatment of PTSD-related nightmares?

While treating Vietnam combat Veterans with PTSD it became clear that trauma nightmares/distressed awakenings were accompanied by intense sympathetic (noradrenergic) arousal symptoms suggesting an “adrenaline storm”. Such an adrenaline storm can be adaptive in combat, but is highly abnormal during sleep and even more abnormal during REM “dreaming stage” sleep. I was familiar with using beta and alph-1 adrenoreceptor (AR) antagonist drugs to treat the excessive adrenergic responsiveness of arterioles in hypertension, and reasoned that such drugs, if able to cross into the brain, might reduce PTSD nightmares and sleep disruption. My first approach was to block brain beta AR with propranolol, which actually exacerbated nightmares in my Veteran patient. Because alpha-1 AR can have opposite effects from beta AR, I turned to the most lipid soluble alpha-1 AR antagonist, which is prazosin. It was effective clinically and confirmed in placebo-controlled studies.

Many mental health providers are hesitant to use prazosin especially at higher doses. What is your advice to these providers?

Providers are often overly concerned about inducing orthostatic hypotension with possible dizziness and syncope with prazosin. Although such “first dose syncope” can occur if prazosin or any alpha-1 AR antagonist (e.g., Flomax) is initiated at a high dose, starting at 1 mg at bedtime for 3 to 7 days then increasing gradually but persistently and teaching patients to assume an upright posture gradually during drug titration obviates this problem. Caveat: erectile dysfunction drugs increase likelihood of orthostatic hypotension, but slow transition from supine to standing is again the best prevention of dizziness. Some Veterans need 20 to 30 mgs of prazosin at bedtime before nightmares resolve and these doses, if approached gradually, rarely cause hypotension. Remember, millions of older men have taken prazosin for years for benign prostatic hyperplasia (BPH) symptomatic relief.

What are your thoughts on using a low daytime dose of prazosin?

Prazosin has a duration of action of 6 to 10 hours, and is prescribed two or three times daily when used for hypertension or BPH. So, if daytime PTSD hyperarousal and re-experiencing symptoms persist even after bedtime prazosin has normalized sleep, I add a 10 AM and 3 PM dose ranging from 1 to 5 mg per dose.

If a patient cannot tolerate prazosin, whatwould be your next agent of choice for treating nightmares? (clonidine, guanfacine, doxazosin?)

It depends on the nature of the adverse effect. Anecdotal data suggest clonidine, an alpha-2 AR agonist that reduces noradrenergic outflow, and doxazosin, a longer acting but less brain penetrating alpha-1 AR antagonist may be useful. Personally, I use flexible dose adjustment to get around “cannot tolerate prazosin”. This usually works.

Many providers feel more comfortable using low dose quetiapine at bedtime for sleep disturbances in PTSD. Do you think this practice is justified?

I do not use it because of risk of weight gain (even at low dose) and common daytime “hangover”. Quetiapine is popular because it has some alpha-1 antagonist activity (and more than most antipsychotics). Unlike prazosin, it helps induce sleep, probably via antihistamine activity. However, it is less effective for nightmares than prazosin unless very large doses are prescribed. If sleep onset difficulty persists in a PTSD patient even when they are no longer reluctant to go to sleep for fear of entering a terrifying trauma nightmare, I prefer a standard hypnotic such as zolpidem or even (perish the thought) a benzodiazepine hypnotic, to augment prazosin.