Doxazosin for the treatment of mental health disorders: A scoping review

TL;DR

This review explores the use of doxazosin, an alpha-1 blocker, for mental health disorders like PTSD and substance use, highlighting its potential and areas needing more research.

Contribution

The paper provides a scoping review of doxazosin's off-label use in mental health, identifying current applications and gaps in evidence.

Findings

Doxazosin shows promise for PTSD-related nightmares and cocaine use disorder.

Most studies are small trials or case reports, with limited evidence for broader applications.

More randomized controlled trials are needed for other PTSD symptoms and substance use disorders.

Abstract

Within the field of psychiatry, the alpha-1 adrenergic antagonist doxazosin is being studied for its off-label uses for disorders involving abnormal sympathetic nervous system arousal, including post-traumatic stress disorder (PTSD) and substance use disorders. Although prazosin is the most well-known alpha-1 antagonist used for these disorders, doxazosin has a longer half-life, which allows for more convenient once-daily dosing. Even though there is an advantage in dosing once daily for doxazosin, the medication is less well-known in the treatment of mental health disorders. The goal of this scoping review is to identify how doxazosin is currently being used in the treatment of mental health disorders, to determine if there is any evidence of its effectiveness for these disorders, and to identify promising areas for further research. PRISMA-ScR guidelines were used to identify articles describing doxazosin for the treatment of mental health disorders in PubMed, Embase, PsycINFO, and CENTRAL to understand current trends in research. Twenty-three articles met the inclusion criteria and included doxazosin for PTSD and/or nightmares, substance use disorders, and dual diagnoses. Many of the articles were small open-label trials or case reports. Existing evidence is strongest for doxazosin’s use in PTSD-related nightmares and cocaine use disorder, which is consistent with the proposed alpha-1 antagonism effect on disorders with high levels of sympathetic nervous system arousal. Current clinical trials continue to be focused on PTSD and cocaine use disorder, given promising evidence. More randomized controlled trials need to be completed for recommendations of doxazosin’s use for other PTSD hyperarousal symptoms (e.g., flashbacks, intrusive thoughts) and other substance use disorders, including nicotine and alcohol use disorders.

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