An adjunct to prolonged exposure therapy for treating refractory PTSD patients

DESCRIPTION provided by applicant The Specific Aim of this proposal is to test the feasibility of using vagus nerve stimulation VNS as an adjunct to prolonged exposure therapy PE for treating PTSD patients who are refractory to PE PE is the treatment of choice for such patients However PE is successful in as few as of cases Refractory PTSD patients have high rates of suicide substance abuse and addiction violent crimes depression and general loss of productivity There is an urgent need to develop a therapy for patients with refractory PTSD PE aims to reduce the conditioned fear response by training patients to develop new situation appropriate responses Treatment of patients with memory enhancing drugs appears to be an effective adjunct to exposure therapy for a number of conditions including PTSD However the number of studies is few and even in those studies there remains a significant number of refractory patients Thus the use of memory enhancing techniques appears promising but more effective options are needed We have found that VNS paired with training can greatly enhance neuroplasticity and rehabilitation in sensory motor and limbic systems These findings include the discovery that pairing VNS with extinction trials increases the rate of extinction in normal rats a study that was supported by a successful Phase I SBIR that set the stage for the current proposal We also demonstrated that VNS pairing with extinction training reverses fear conditioning related synaptic changes in the rat brain and collected preliminary data showing that we can produce a well established rodent model of PTSD in our laboratory We have a record of extending our positive VNS pairing findings in pre clinical animal models to clinically meaningful results in humans for tinnitus and stroke Because these clinical findings were both predicted by our pre clinical animal models it is reasonable to test pairing VNS with PE to reverse the effects of conditioned fear in refractory PTSD patients if animal studies support such a therapy While we previously demonstrated positive effects in a rat model of fear conditioning to test feasibility of moving our therapy forward in refractory patients we will cary out a study in a model of refractory PTSD To this end we will use a rat model of PTSD in which rats are resistant refractory to extinction Single Prolonged Stressor SPS Test of Feasibility The VNS group must show complete reversal of the fear response following extinction The reversal in the VNS SPS group must be larger than any reversal in the Sham stimulated SPS group P andlt See Experimental section for more details Phase II will use parametric studies for improving stimulation parameters while working with PTSD clinicians and PE therapists to develop the protocol to pair therapy with VNS PUBLIC HEALTH RELEVANCE Posttraumatic stress disorder PTSD is an increasing public health concern According to the National Center for PTSD NCPTSD approximately of the US population suffers from PTSD The disorder is often accompanied by severe depression anxiety substance abuse suicide and crime A large fraction of PTSD patients are refractory to all current treatments This project aims to develop the first effective therapy for treating this population of refractory patients