Doxazosin Shows Potential as Alternative PTSD-Related Nightmare Treatment

Antihypertensive drug doxazosin may serve as a viable alternative treatment for PTSD-related nightmares while improving on the risk of incident hypotension associated with prazosin, according to new data.

Findings presented at the American Psychiatric Association (APA) 2024 Annual Meeting in New York, NY this week showed a promising, albeit incomplete, efficacy and safety profile for doxazosin in the treatment of PTSD-related symptoms including nightmares. Investigators noted this clinical development is further indicative of the potential utility of alpha-1 adrenergic antagonists, including doxazosin and prazosin, in treating PTSD and possibly other psychiatric pathologies.

Investigators conducted a comprehensive literature review evaluating the efficacy and safety of doxazosin in normotensive patients with PTSD who report nightmares associated with their psychiatric condition. They noted that prazosin in particular has been well studied for the treatment of PTSD nightmares, which are generally characterized by intrusive memories that result in a heightened arousal in patients. Doxazosin, they wrote, has been considered a potential alternative to treatment for some time.

“It shares the alpha-1 adrenergic antagonist mechanism but offers pharmacokinetic advantages including a longer half-life that allows for once-daily dosing and slower peak plasma levels potentially reducing the risk of hypotension and orthostatic events,” the team wrote. “Despite these benefits, questions remain about doxazosin’s safety profile in the PTSD population—a concern this literature review aims to address.”

Investigators conducted a comprehensive literature search via PubMed and Embase for relevant clinical research regarding the efficacy and safest of doxazosin in the treatment of PTSD. Their inclusion criteria required research be peer-reviewed, published after 1983, and including human trials or case series reports involving adults aged ≥18 years old.

The team sought quantitative outcome measures including blood pressure values per mmHg, nightmare cessation, dosage of treatment, and response after time of administration. They also sought qualitative measures including adverse events reported while receiving doxazosin.

The APA 2024 abstract reported that the overall incidence of hypotension associated with doxazosin was low among patients with PTSD, and lower than that observed with prazosin. In fact, the investigators noted doxazosin seemed to offer fewer adverse events overall than prazosin. They also believed that dosing levels and formulation type (i.e., standard versus gastrointestinal therapeutic system [GITS]) seemed to influence incidence of hypotension.

“The drug’s longer half-life contributes to maintenance of effect throughout the night which may facilitate improved adherence,” the team wrote. “While orthostatic hypotensive events were reported in some studies, it can be largely attributed to the first dose effect and the impact was generally not severe enough to discontinue treatment.”

Investigators concluded that doxazosin provided lower incidence of treatment-related adverse events to prazosin in the treatment of PTSD-related nightmares—though more research is warranted to conclusively establish its safety profile in relevant patients. The agent may hold potential in psychiatric treatment.

“This review adds to a growing body of literature regarding off-label use of alpha-1 adrenergic antagonists for the treatment of PTSD and other pathologies within the field of psychiatry,” investigators wrote.

References

1. ^{Regan K, et al. Evaluating the Safety and Efficacy of Doxazosin in Managing PTSD-Related Nightmares Among Normotensive Patients: A Comprehensive Literature Review. Paper presented at: American Psychiatric Association (APA) 2024 Annual Meeting. New York, NY. May 4-8, 2024.}
2. ^{Paiva HS, Filho IJZ, Cais CFDS. Using Prazosin to Treat Posttraumatic Stress Disorder and Associations: A Systematic Review. Psychiatry Investig. 2021;18(5):365-372. doi:10.30773/pi.2020.0411}