Repurposed therapeutics for the treatment of post-traumatic stress disorder (PTSD) symptoms as well as other anxiety-related disorders.
- The renin-angiotensin pathway is a new target pathway for the treatment of PTSD.
- Drugs are FDA approved for hypertension and have an excellent safety profile with few side effects.
PTSD is prevalent in highly traumatized civilian population as well as among soldiers returning from combat-military operations. It is estimated that as much as 15% of the US population may develop PTSD at some time due to traumatic events in their life. The global PTSD therapeutics market is worth over a billion dollars. While the relationship between the renin-angiotensin system and stress has been previously demonstrated in hypertension and renal and cardiovascular diseases, ACE-I or ARB treatment for PTSD or other anxiety disorders has not been actively pursued. Current therapeutics for PTSD primarily target neurotransmitters such as serotonin or dopamine and are used in combination with cognitive behavioral therapy. The available medications either suffer from a range of harsh side effects or are effective for short-term management only. A defined drug treatment option does not exist, further illustrating the need for additional therapies.
The renin-angiotensin pathway is a hormonal system essential for mediating stress and anxiety. Over-activation of this system is a known cause of elevated blood pressure. A relationship has been drawn between certain existing blood pressure medications and the reduction of positive symptoms of PTSD, including hyper arousal, intrusive thoughts, nightmares, re-experiencing, hyper vigilance and hyperactive sympathetic activation, but a connection between angiotensin and PTSD was previously unknown.
Researchers at Emory have demonstrated a correlation between active treatment with ACE-I or ARB and PTSD symptom severity in a clinical retrospective observational study of a highly traumatized civilian medical population. Based on the results of this study, the investigators examined the effect of losartan, a specific angiotensin II receptor blocker, in an animal model of anxiety using fear conditioning. This study confirmed the human retrospective study with a reduction in fear conditioning following administration of losartan. These findings suggest that a treatment which blocks angiotensin activation may be advantageous for decreasing fear responses and enhancing the extinction of fear memories related to PTSD, as well as other anxiety-related psychiatric diseases.
Proof-of-principle study in animal model of anxiety has been completed confirming the retrospective human study analysis.
Publications: Khoury N et al. J. of Clin. Psych. 73(6):849-955. (2012).