Mr. H, age 43, presents to your clinic for management of posttraumatic stress disorder (PTSD). At his last appointment 8 weeks ago, he was continued on fluoxetine, 60 mg/d; he had been stable on this medication for 6 months. Today, Mr. H reports an increase in the frequency and severity of nightmares. He states that he wakes at least 3 times every week with “disturbing dreams” about his time in the military and does not feel rested even when he sleeps through the night. His Clinician-Administered PTSD Scale (CAPS) score is 95 on this visit, suggesting extreme PTSD symptomatology. Mr. H asks if anything can be done to reduce the frequency and intensity of his nightmares.
PTSD is the development of characteristic symptoms following exposure to ≥1 traumatic events. According to DSM-5, PTSD symptoms include the presence of ≥1 intrusion symptoms (recurrent, intrusive memories of the traumatic event; recurrent distressing dreams; dissociative reactions), persistent avoidance of stimuli, negative alterations in cognition and mood, and marked alterations in arousal and reactivity associated with the traumatic event(s).1 The symptoms must be present for >1 month, cause clinically significant distress or impairment in functioning, and not be attributable to the psychologic effects of a substance or medical conditions.1 This article focuses specifically on the hyperarousal symptoms, and the clinical controversies surrounding the use of prazosin for PTSD.
Prazosin for PTSD treatment
Sleep disorders are extremely common in patients with PTSD. Up to 90% of patients report sleep disturbances, and up to 70% report nightmares.2 Prazosin has been widely used in the treatment of PTSD-related sleep disorders and nightmares.The American Psychiatric Association3 and the British Association of Psychopharmacology4 guidelines in-clude prazosin as a first-line recommendation for treatment of PTSD. However, updated 2017 guidelines from the Veterans Affairs/Department of Defense (VA/DoD)5 and data from the 2018 Prazosin and Combat Trauma PTSD (PACT) trial6 contradict these original recommendations. Previously, the 2010 VA/DoD guideline said prazosin had insufficient evidence for monotherapy, but recommended it as adjunctive treatment for sleep and nightmares.7 The updated 2017 VA/DoD guideline recommends “weak against” prazosin use for global symptoms of PTSD, and says there is insufficient evidence for its use in nightmares.5 Below we summarize the findings of studies that contributed to those original recommendations, along with results of the PACT trial.
Raskind et al8,9 conducted 2 studies of prazosin use in combat veterans with PTSD. In both studies, prazosin had significant positive effects on the Clinician-Administered PTSD Scale (CAPS) and Clinical Global Impression of Change (CGIC) scores.8,9 The 2007 study also found significant effects of prazosin on Pittsburgh Sleep Quality Index (PSQI) scores.9
Raskind et al10 conducted another study in 2013 of prazosin use for active-duty soldiers who had combat trauma PTSD with nightmares. Prazosin had positive effects for nightmares, sleep quality, and CAPS scores.10
Germain et al11 reviewed prazosin for treating sleep disturbances in US military veterans. Prazosin was associated with significant improvements in insomnia and daytime PTSD symptom severity as demonstrated by changes in PSQI and CAPS scores.11
Taylor et al12 examined the effects of prazosin on sleep measures and clinical symptoms in civilians with PTSD. Prazosin significantly increased total sleep time, rapid eye movement sleep time, and CGIC scores while significantly decreasing trauma-related nightmares.12
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