We return to Norma, a 70 yo woman with hypertension and post-traumatic stress disorder (PTSD). After the death of her husband, she experienced a major depressive episode and a resurgence of PTSD symptoms from a sexual assault in her 20s. She started sertraline, but stopped due to side effects. EMDR, an evidence based trauma focused therapy, was effective for her, and she has been well without medications or ongoing therapy for the past 5 years.
One month ago, Norma heard a man in her apartment at 2am and thought that she was going to be raped. The man was a maintenance worker responding to an emergency call of water dripping into the downstairs apartment. Since that night, Norma wakes up with nightmares of the previous sexual assault 2-3x/night and sleeps with a knife under her pillow for protection. She has only been sleeping 2-3 hours nightly. Norma now has flashbacks multiple times a day, startles easily, and avoids leaving her apartment.
Norma called her previous EMDR therapist who has availability in 3 months. She comes to you, her primary care clinician, for help. She doesn’t want to try another antidepressant, given her previous experience with sertraline, but she is open to trying a different kind of medication.
What medications can reduce nightmares and improve sleep in people with PTSD?
Decreased sleep can lead to irritability, anxiety, low mood, and a decreased ability to cope with stressors, which in turn can worsen insomnia. This vicious cycle between poor sleep and worsened mental health symptoms can also be reversed. For people with PTSD, improvements in sleep can lead to improvements in PTSD symptoms more globally.
Prazosin is a generically-available, alpha-1 noradrenergic receptor antagonist that addresses the autonomic hyperarousal that is common in PTSD. Recent meta-analyses show that in people with PTSD, prazosin has a medium effect size in reducing nightmares and sleep quality, and a small effect size in reducing overall PTSD symptoms (Burback 2024). The evidence from RCTs for prazosin is mixed, and prazosin does not have FDA approval for nightmares associated with PTSD. Early studies and meta-analyses of prazosin for nightmares associated with PTSD were overwhelmingly positive. However, in the largest randomized controlled study to date, prazosin failed to separate from what turned out to be an unusually effective pill placebo (Raskind 2016). Even so, in considering all of the prior studies, the 2023 National Veterans Administration (VA) guidelines recommend prazosin for the treatment of nightmares associated with PTSD.
I offer prazosin to patients with PTSD and frequent nightmares or sleep disturbances. It can sometimes help nightmares within days of starting it, providing patients with a positive experience with a psychiatric medication relatively quickly. I have had several patients who are more willing to consider a 1st line medication for PTSD (sertraline, paroxetine, venlafaxine) after having had a positive experience with prazosin. Although some patients benefit quickly from prazosin, don’t give up on a prazosin trial for lack of efficacy until you hit the max dose tolerated for at least several weeks.
Prazosin dosing and patient counseling
When treating nightmares associated with PTSD, I start prazosin at 1mg at bedtime, increasing to 2mg after 4 days. Prazosin can then be titrated by 2mg q1-2 weeks up to 10mg, the maximum recommended dose for women, and up to prazosin 15mg for men. Stop the titration when nightmares resolve or side effects limit further titration. Most of my patients who benefit from prazosin take 2-5mg, but the literature suggests that higher doses are tolerable and necessary for some people.
If a patient has daytime hyperarousal symptoms or distress from trauma related cues, a mid-morning dose (10am) of prazosin that is roughly one-third the bedtime dose may help.
Counsel patients, in particular older adults, about the risk of next day fatigue and orthostasis. Prazosin has a short half-life of 2-4 hours with a duration of action of 6-10 hours. This helps to prevent daytime fatigue with nighttime dosing. While prazosin is often well-tolerated, patients who are taking other antihypertensive agents or phosphodiesterase 5 inhibitors like sildenafil may experience additive hypotensive effects from prazosin.
Some clinicians have also started using doxazosin for PTSD. Doxazosin is a once daily “me too” drug of prazosin (i.e. an alpha-1 noradrenergic receptor antagonist) with a lower risk of orthostasis than prazosin and a longer half-life (16-30 hours). Evidence to support using doxazosin for nightmares associated with PTSD is limited to case reports and open label trials.
In choosing among different alpha-1 antagonists for sleep disturbances associated with PTSD, I generally start with prazosin given the more robust literature to support its use. If prazosin side effects like orthostasis are problematic, or if a patient benefits from, but is struggling with twice daily dosing, I would switch to doxazosin (extended release, start at 4mg at night, target dose 4-16mg).
If a patient’s nightmares resolve for several months on prazosin, it is reasonable to gradually taper it with close clinical follow-up. See the end of this previous PsychSnap for more information on de-prescribing prazosin.
Patient instructions for prazosin (Copy me into your EMR; change text color to black):
Prazosin can help with nightmares and sleep disturbances associated with PTSD. It is generally well-tolerated. You may develop dizziness, lightheadedness or headaches from prazosin. Be sure to stand up slowly, especially when you first start the medication. Sit for a minute or two prior to getting out of bed or a bath. Prazosin can sometimes make people tired or groggy in the morning. Let me know if you experience any of these side effects. Prazosin can very rarely cause priapism, a sustained erection that does not go away, requiring treatment in an emergency room.
Initial dosing of prazosin 1mg capsules:
Take 1 capsule at bedtime for 4 days. If you are tolerating it well, increase to 2 capsules (2mg) at bedtime.
Back to Norma
You recommend that Norma start taking prazosin 1mg at bedtime. She feels a little dizzy in the morning after the first dose and does not increase the dose to 2mg as planned. When you see her 3 weeks later, she is still taking prazosin 1mg. Her sleep has improved remarkably – she no longer has nightmares and doesn’t wake up in the middle of the night. She refers to prazosin 1mg as her sleeping pill.
Key Points
- Prazosin is an alpha-one noradrenergic antagonist that reduces sleep disturbances and nightmares associated with PTSD with a medium effect size.
- Prazosin is generally well-tolerated – titrate it slowly, starting at 1mg, due to the risk of orthostasis. If side effects are problematic, doxazosin is a reasonable alternative.
Related PsychSnaps:
“What are first-line treatments for PTSD?” Emma Samelson-Jones, July 2024.
“How do you know when a patient has recovered from PTSD and you can consider de-prescribing medication?” Zoë Kopp, June 2024.
References:
Burback, Lisa, et al. “Treatment of posttraumatic stress disorder: a state-of-the-art review.” Current Neuropharmacology 22.4 (2024): 557.
VA/DoD Clinical Practice Guideline. (2023). Management of Posttraumatic Stress Disorder and Acute Stress Disorder Work Group. Washington, DC: U.S. Government Printing Office.
Raskind, Murray A., et al. “Trial of prazosin for post-traumatic stress disorder in military veterans.” New England Journal of Medicine 378.6 (2018): 507-517.
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