J Clin Psychiatry. 2012 Jun;73(6):849-55
Khoury NM, Marvar PJ, Gillespie CF, Wingo A, Schwartz A, Bradley B, Kramer M, Ressler KJ
Abstract
OBJECTIVE: Posttraumatic stress disorder (PTSD) is a debilitating stress-related illness associated with trauma exposure. The peripheral and central mechanisms mediating stress response in PTSD are incompletely understood. Recent data suggest that the renin-angiotensin pathway, essential to cardiovascular regulation, is also involved in mediating stress and anxiety. In this study, the authors examined the relationship between active treatment with blood pressure medication, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and PTSD symptom severity within a highly traumatized civilian medical population.
METHOD: Cross-sectional, observational data were analyzed from a larger study; patients were recruited from Grady Memorial Hospital’s outpatient population from 2006 to November 2010. Multivariable linear regression models were fit to statistically evaluate the independent association of being prescribed an ACE inhibitor or ARB with PTSD symptoms, using a subset of patients for whom medical information was available (n = 505). Categorical PTSD diagnosis was assessed using the modified PTSD Symptom Scale (PSS) based on DSM-IV criteria, and PTSD symptom severity (the primary outcome of interest) was measured using the PSS and Clinician Administered PTSD Scale.
RESULTS: A significant association was determined between presence of an ACE inhibitor/ARB medication and decreased PTSD symptoms (mean PSS score 11.4 vs 14.9 for individuals prescribed vs not prescribed ACE inhibitors/ARBs, respectively [P = .014]). After adjustment for covariates, ACE inhibitor/ARB treatment remained significantly associated with decreased PTSD symptoms (P = .044). Notably, other blood pressure medications, including β-blockers, calcium channel blockers, and diuretics, were not significantly associated with reduced PTSD symptoms.
CONCLUSIONS: These data provide the first clinical evidence supporting a role for the renin-angiotensin system in the regulation of stress response in patients diagnosed with PTSD. Further studies should examine whether available medications targeting this pathway should be considered for future treatment and potential protection against PTSD symptoms.PMID: 2268763
Most practitioners do not realize that the renin-angiotensin-aldosterone pathway is incomplete until you include the sympathetic branch of the nervous system and the histamine systems.
The actual system forms a signaling positive feedback loop: Norepinephrine + Histamine -> Renin -> Angiotensin II -> Aldosterone -> Norepinephrine + Histamine. There are other pro-inflammatory signals that are also increased. As a positive feedback loop, the system, once started, is self-perpetuating unless the loop is broken by other molecules.
ACE inhibitors and ARBS partially slow the loop down. There is a renin kickback that will counteract there actions.
ACE inhibitors and to a lesser extent ARBS also have distinct actions within the central nervous system independent of the peripheral effects. ACE inhibitors may be considered in some aspects as nootropics. These central effects may be also in play in reducing PTSD symptoms.
The study didn’t consider an older blood pressure medication – Clonidine – that clearly can also reduce PTSD symptoms. It was studied years ago as a treatment for PTSD.