Is there any human research or experience with HDAC inihibitors?
My own preference would be to look to drugs where there is at least *some* evidence of benefit (for PTSD) in humans...
Some of the SSRIs are FDA approved for PTSD. If you are looking for something a little more experimental, what about angiotensin receptor blockers (ARBs) such as telmisartan:
J Clin Psychiatry. 2012 Jun;73(6):849-55. doi: 10.4088/JCP.11m07316. Epub 2012 May 1.
The renin-angiotensin pathway in posttraumatic stress disorder: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are associated with fewer traumatic stress symptoms.
Khoury NM1, 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.
© Copyright 2012 Physicians Postgraduate Press, Inc.
Yes, this research is observational, but it's better than nothing... and ARBs have been thoroughly investigated in people (for hypertension) & so their safety profile is known...
Here is a nice summary of some related research (animal model research, looking for a mechanism that might explain the observational findings, above):
Common Hypertension Treatment May Reduce PTSD Symptoms
June, 2014
There are currently only two FDA-approved medications for the treatment of posttraumatic stress disorder (PTSD) in the United States. Both of these medications are serotonin uptake inhibitors. Despite the availability of these medications, many people diagnosed with PTSD remain symptomatic, highlighting the need for new medications for PTSD treatment.
The renin-angiotensin system has long been of interest to psychiatry. Some of the first drugs targeting this system were the angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), commonly prescribed treatments for high blood pressure.
In the 1990's, multicenter studies evaluating ACE inhibitors suggested that they improved quality of life as well as other medical outcomes, but these medications did not prove to be sufficiently effective for the treatment of psychiatric disorders to become established treatments.
Recently, however, investigators at Emory University observed that individuals diagnosed with PTSD, and who happened to also be treated with ARBs or ACE inhibitors, exhibited fewer PTSD-like symptoms.
This led the researchers to investigate the underlying mechanisms using an animal model of PTSD in order to expand upon this clinical finding.
Dr. Paul Marvar, first author and Assistant Professor at The George Washington University, explains their findings, "Our current preclinical results show that the ARB losartan, given acutely or chronically to mice, enhances the extinction of fear memory, a process that is disrupted in individuals with PTSD. Overall these data provide further support that this class of medications may have beneficial effects on fear memory in PTSD patients."
Fear extinction is a process by which a memory associated with fear is gradually 'overwritten' in the brain by a new memory with no such association. For example, exposure therapy is a form of fear extinction, whereby repeatedly exposing a patient in a safe manner to a feared object or situation slowly reduces or eliminates their fear. A medication that could potentially enhance the extinction of fear would be welcome to the millions of individuals who continue to suffer with symptoms of PTSD...
Edited by blood, 05 October 2014 - 09:50 AM.