Citation:
McCall WV. Alpha-1 adrenergic antagonists use increases the risk of sleep apnea: implications for understanding the role of prazosin in posttraumatic stress syndrome. J Clin Sleep Med. 2020;16(4):643.
I was intrigued by the recent report from Su et al1 that use of α1-adrenergic antagonists increases the risk of developing sleep apnea. Their study was an observational study of a large population, not a clinical trial. Still, their finding raises an interesting explanation for why prazosin is reported to be helpful in some but not all patients with posttraumatic stress disorder (PTSD). Prazosin is an α1-adrenergic antagonist and has been proposed as a treatment of PTSD symptoms, especially PTSD nightmares.2
Prazosin studies have variously shown a beneficial effect in PTSD in active duty soldiers,3 no benefit/worsening of PTSD in military veterans,4 or worsening of PTSD in one small sample of mostly nonmilitary patients with PTSD.5 Other investigators have raised the possibility of high rates of sleep apnea in PTSD patients, but none of the aforementioned prazosin studies assessed for sleep apnea.6 Although the report of Su et al is not the last word on the topic of α-antagonists and sleep apnea, for now their findings raise the possibility that prazosin induces or worsens sleep apnea in some patients with PTSD or nightmares, contributing to the heterogeneity of clinical trial results of prazosin for PTSD and nightmares. Future clinical trials of prazosin or other α1-adrenergic blockers for PTSD and nightmares may need to test for obstructive sleep apnea at baseline and during treatment.
DISCLOSURE STATEMENT
All authors have seen and approved the manuscript. Dr. McCall receives royalties from Wolters Kluwer and research support from Merck, MECTA, PCORI, and Vistagen. He has been a consultant for Sage and Jazz. The authors report no conflicts of interest. The authors report the off-label/investigational use of prazosin for the treatment of posttraumatic stress disorder.
REFERENCES
- 1.Su P-L, Lin W-K, Lin C-Y, et al. Alpha-1 adrenergic-antagonist use increases the risk of sleep apnea: a nationwide population-based cohort study. J Clin Sleep Med. 2019;15(11):1571–1579. doi: 10.5664/jcsm.8014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.George K, Kebejian L, Ruth LJ, et al. Meta-analysis of the efficacy and safety of prazosin versus placebo for the treatment of nightmares and sleep disturbances in adults with posttraumatic stress disorder. J Trauma Dissociation. 2016;17(4):494–510. doi: 10.1080/15299732.2016.1141150. [DOI] [PubMed] [Google Scholar]
- 3.Raskind MA, Peterson K, Williams T, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013;170(9):1003–1010. doi: 10.1176/appi.ajp.2013.12081133. [DOI] [PubMed] [Google Scholar]
- 4.Raskind MA, Peskind ER, Chow B, et al. Trial of prazosin for post-traumatic stress disorder in military veterans. N Engl J Med. 2018;378(6):507–517. doi: 10.1056/NEJMoa1507598. [DOI] [PubMed] [Google Scholar]
- 5.McCall W, Pillai A, Case D, et al. A pilot, randomized clinical trial of bedtime doses of prazosin versus placebo in suicidal posttraumatic stress disorder patients with nightmares. J Clin Psychopharmacol. 2018;38(6):618–621. doi: 10.1097/JCP.0000000000000968. [DOI] [PubMed] [Google Scholar]
- 6.Krakow B, Ulibarri V, Moore B, et al. Posttraumatic stress disorder and sleep-disordered breathing: a review of comorbidity research. Sleep Med Rev. 2015;24:37–45. doi: 10.1016/j.smrv.2014.11.001. [DOI] [PubMed] [Google Scholar]