ABSTRACT
Objective: Antihypertensive medications have been examined as agents for posttraumatic stress disorder (PTSD) prevention in trauma-exposed individuals, given well-documented associations between PTSD and increased risk of cardiovascular disease and purported trauma-relevant mechanisms of action for these medications. Evidence regarding the effectiveness of such drugs for this purpose remains mixed.
Methods: We conducted a national population-based cohort study using data from Danish national registries to assess whether 4 classes of antihypertensive drugs (beta-adrenoceptor blockers [beta blockers], angiotensin II receptor blockers [ARBs], angiotensin-converting enzyme [ACE] inhibitors, and calcium channel blockers) were associated with a decreased incidence of PTSD (diagnosed according to ICD-10) over a 22-year study period. Data for this study originated from a population-based cohort of over 1.4 million persons who experienced a traumatic event between 1994 and 2016 in Denmark. We calculated the incidence rate of PTSD per 100,000 person-years among persons who filled a prescription for each class of drug in the 60 days prior to a traumatic event and for corresponding unexposed comparison groups. We then used Cox proportional hazards regression to compare the rate of PTSD among persons who filled an antihypertensive medication prescription within 60 days before their trauma to the rate among persons who did not.
Results: We found evidence that calcium channel blockers were associated with a decreased incidence of PTSD (adjusted hazard ratio = 0.63, 95% confidence interval [CI] = 0.34, 1.2); all other antihypertensive medication classes had null or near null associations.
Conclusions: These findings lay a foundation for additional research focusing on antihypertensive medications that appear most effective in reducing PTSD incidence following trauma and for additional replication work aimed at continuing to clarify the disparate findings reported in the literature to date.
J Clin Psychiatry 2023;84(5):22m14767
Author affiliations are listed at the end of this article.
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References (30)
- Sumner JA, Cleveland S, Chen T, et al. Psychological and biological mechanisms linking trauma with cardiovascular disease risk. Transl Psychiatry. 2023;13(1):25. PubMed CrossRef
- Argolo FC, Cavalcanti-Ribeiro P, Netto LR, et al. Prevention of posttraumatic stress disorder with propranolol: a meta-analytic review. J Psychosom Res. 2015;79(2):89–93. PubMed CrossRef
- Cojocariu SA, Maștaleru A, Sascău RA, et al. Neuropsychiatric consequences of lipophilic beta-blockers. Medicina (Kaunas). 2021;57(2):155. PubMed CrossRef
- Pitman RK, Sanders KM, Zusman RM, et al. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry. 2002;51(2):189–192. PubMed CrossRef
- Seligowski AV, Duffy LA, Merker JB, et al. The renin-angiotensin system in PTSD: a replication and extension. Neuropsychopharmacology. 2021;46(4):750–755. PubMed CrossRef
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. American Psychiatric Association Publishing; 2013.
- Armstrong C, Kapolowicz MR. A preliminary investigation on the effects of atenolol for treating symptoms of anxiety. Mil Med. 2020;185(11–12):e1954–e1960. PubMed CrossRef
- Garakani A, Mathew SJ, Charney DS. Neurobiology of anxiety disorders and implications for treatment. Mt Sinai J Med. 2006;73(7):941–949. PubMed
- Levy A, Kadar T, Dachir S. An animal model for studying therapeutic drugs against post-traumatic stress disorder. Mil Med. 2001;166(suppl):74–75. PubMed CrossRef
- Verma M, Bali A, Singh N, et al. Investigating the role of nisoldipine in foot-shock-induced post-traumatic stress disorder in mice. Fundam Clin Pharmacol. 2016;30(2):128–136. PubMed CrossRef
- Colbourne L, Harrison PJ. Brain-penetrant calcium channel blockers are associated with a reduced incidence of neuropsychiatric disorders. Mol Psychiatry. 2022;27(9):3904–3912. PubMed CrossRef
- Khoury NM, Marvar PJ, Gillespie CF, et al. The renin-angiotensin pathway in posttraumatic stress disorder: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are associated with fewer traumatic stress symptoms. J Clin Psychiatry. 2012;73(6):849–855. PubMed CrossRef
- Nylocks KM, Michopoulos V, Rothbaum AO, et al. An angiotensin-converting enzyme (ACE) polymorphism may mitigate the effects of angiotensin-pathway medications on posttraumatic stress symptoms. Am J Med Genet B Neuropsychiatr Genet. 2015;168B(4): 307–315. PubMed CrossRef
- Marvar PJ, Goodman J, Fuchs S, et al. Angiotensin type 1 receptor inhibition enhances the extinction of fear memory. Biol Psychiatry. 2014;75(11):864–872. PubMed CrossRef
- Quiñones MM, Maldonado L, Velazquez B, et al. Candesartan ameliorates impaired fear extinction induced by innate immune activation. Brain Behav Immun. 2016;52:169–177. PubMed CrossRef
- Saavedra JM, Sánchez-Lemus E, Benicky J. Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: therapeutic implications. Psychoneuroendocrinology. 2011;36(1):1–18. PubMed CrossRef
- Shekhar A. Angiotensin type 1 receptor antagonists-a novel approach to augmenting posttraumatic stress disorder and phobia therapies? Biol Psychiatry. 2014;75(11):836–837. PubMed CrossRef
- Stein MB, Jain S, Simon NM, et al; LOSe-PTSD Investigators. Randomized, placebo-controlled trial of the angiotensin receptor antagonist losartan for posttraumatic stress disorder. Biol Psychiatry. 2021;90(7):473–481. PubMed CrossRef
- Gradus JL, Rosellini AJ, Szentkúti P, et al. Using Danish national registry data to understand psychopathology following potentially traumatic experiences. J Trauma Stress. 2022;35(2):619–630. PubMed CrossRef
- Schmidt M, Schmidt SAJ, Sandegaard JL, et al. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol. 2015;7:449–490. PubMed CrossRef
- Mors O, Perto GP, Mortensen PB. The Danish Psychiatric Central Research Register. Scand J Public Health. 2011;39(suppl):54–57. PubMed CrossRef
- Bliddal M, Broe A, Pottegård A, et al. The Danish medical birth register. Eur J Epidemiol. 2018;33(1):27–36. PubMed CrossRef
- Helweg-Larsen K. The Danish register of causes of death. Scand J Public Health. 2011;39(suppl):26–29. PubMed CrossRef
- World Health Organization. International Statistical Classification of Diseases and Related Health Problems: Instruction Manual. World Health Organization; 2004:2.
- Svensson E, Lash TL, Resick PA, et al. Validity of reaction to severe stress and adjustment disorder diagnoses in the Danish Psychiatric Central Research Registry. Clin Epidemiol. 2015;7:235–242. PubMed CrossRef
- Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. PubMed CrossRef
- Wasserstein RL, Schirm AL, Lazar NA. Moving to a world beyond “p < .05.” Am Stat. 2019;73(sup 1):1–19. CrossRef
- Amrhein V, Greenland S, McShane B. Scientists rise up against statistical significance. Nature. 2019;567(7748):305–307. PubMed CrossRef
- Lash TL. The harm done to reproducibility by the culture of null hypothesis significance testing. Am J Epidemiol. 2017;186(6):627–635. PubMed CrossRef
- McShane BB, Gal D, Gelman A, et al. Abandon statistical significance. Am Stat. 2019;73(sup 1):235–245. CrossRef
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