Prazosin and doxazosin for PTSD are underutilized and underdosed
Often, clinicians tend to focus on the diagnosis and treatment of psychiatric disorders, such as psychosis, bipolar disorder, depression, anxiety, insomnia, and substance use disorders (SUD), but posttraumatic stress disorder (PTSD) often is overlooked and underdiagnosed,1 especially when comorbid with another psychiatric disorder such as SUD.
Targeting mechanisms of action
Noradrenergic mechanisms have been strongly implicated in the pathophysiology of PTSD. However, selective serotonin reuptake inhibitors, such as sertraline and paroxetine, are the only FDA-approved pharmacotherapy options for PTSD, although their efficacy is limited, perhaps because they are serotonergic.
Prazosin, an alpha-1 (α-1) adrenergic antagonist that is FDA-approved for hypertension and benign prostatic hypertrophy, has been studied for treating nightmares in PTSD.7 Prazosin has shown efficacy for nightmares in PTSD and other daytime symptoms, such as flashbacks, hypervigilance, and irritability.8 Several studies support the efficacy of prazosin in persons suffering from PTSD.9-11 Use of lower dosages in clinical trials might explain why prazosin did not separate from placebo in some studies. (See Table summarizing studies of prazosin dosing for PTSD.)
In a study of 12,844 veterans, the mean maximum prazosin dosage reached in the first year of treatment was 3.6 mg/d, and only 14% of patients reached the minimum Veterans Affairs recommended dosage of 6 mg/d.17 The most recent (March 2009) American Psychiatric Association practice guidelines recommend prazosin, 3 to 15 mg at bedtime.18
Prazosin has a short half-life of 2 to 3 hours and duration of action of 6 to 10 hours. Therefore, its use is limited to 2 or 3 times daily dosing. Higher (30 to 50 mg) and more frequent (2 to 3 times per day) dosages8,12,13 might be needed because of the drug’s short half-life.
Doxazosin. Another α-1 adrenergic drug, doxazosin, 8 to 16 mg/d, has shown benefit for PTSD as well.14,15 Doxazosin, which has a longer half-life (16 to 30 hours), requires only once-daily dosing.16 The most common side effects of prazosin and doxazosin are dizziness, headache, and drowsiness; syncope has been reported but is rare.
Prazosin and doxazosin also are used to treat substance abuse, such as alcohol use disorder19-21 and cocaine use disorder.22,23 This “two birds with one stone” approach could become more common in clinical practice.
Until a major breakthrough in PTSD treatment emerges, prazosin and doxazosin, although off-label, are reasonable treatment approaches.
