About This Research Project
Harpaz-Rotem, Ilan PhD ABPP
Associate Professor in the Department of Psychiatry
Yale University School of Medicine
Harpaz-Rotem, Ilan PhD ABPPhas been treating and investigating PTSD for the past 17 years.
Combining neurobiology and new learning – Ketamine and Prolonged exposure (PE): A potential rapid treatment for PTSD
The overall goal of the proposed study is to provide more effective and long-lasting treatment for PTSD as about 50% of individuals diagnosed with PTSD do not improve with the currently available treatments. New scientific results in controlled clinical trials, reported a significant positive effect of Ketamine on alleviating depressive symptoms. Additional laboratory results show that Ketamine creates new neural connections in brain areas that previously suffered significant atrophy due to prolonged stress. Based on these findings, we propose to harvest the effect of ketamine on the brain to enhance new learning in patients suffering from chronic PTSD. After infusion of Ketamine at a subanesthetic dose, new neuronal connections in areas associated with memory and learning are formed, potentially allowing to improve learning and help to rethink old memories. In the proposed treatment study, we will focus on helping patients to enhance their capacity to deal with intrusive memories of the trauma and their ability to overwrite unrealistic fears that are remanences of their exposure to trauma. We will use a double-blind placebo-controlled design (both patient and doctor are not aware of which drug the patient receives). The present investigation aims to examine the efficacy of a single dose of ketamine infusion as compared to an active placebo (midazolam) in combination with intensive one-week exposure therapy with the goal of producing a rapid and sustained reduction in PTSD symptomatology.
PTSD is a debilitating and chronic mental illness. There are currently only two FDA-approved medications for the treatment of PTSD, both of which may take weeks to months to reach full clinical effects. The rates of nonresponse to these selective serotonin reuptake inhibitor antidepressants are high. Therefore, there is a tremendous need to test novel pharmacological approaches to PTSD. It was recently demonstrated that an intensive 7-day cognitive-behavioral treatment for PTSD might be as effective as a 3-month weekly treatment.
Taken together, we propose to employ exposure therapy during the period of enhanced neuroplasticity following a single infusion of Ketamine. During the enhanced neuroplasticity window we will work emphatically with patients to enhance their capacity to better process their traumatic memories and help them to confront safely their fearful behavior. This may lead to both reduction of re-experiencing symptoms, while the real-life exposure (confronting avoidance behavior in a safe environment) will reduce fear-led avoidant behavior and exaggerated startle responses. Thus, this potential intervention would tackle all PTSD symptoms simultaneously in a single one-week-long treatment.
In addition, we will also use MRI scans to assess changes in the brain during the course of the treatment to identify unique biomarkers that interact with the proposed intervention. We propose to evaluate the changes in brain connectivity between areas that are important for fear extinction and the promotion of new learning (such as the amygdala, hippocampus, and prefrontal cortex) and whether these changes predict treatment response. It is also important to link the connectivity changes to changes in brain activation during exposure to trauma reminders. Personal trauma narratives will be presented during fMRI scan to assess changes in responses to fear pre-post treatment.
We are requesting additional funds to extend this project. By enrolling additional participants to increase statistical power, we will further investigate our preliminary findings which indicate that individuals treated with ketamine showed better long-term outcomes.
Adult men and women with PTSD, English speaking, age 21 and older
Harpaz-Rotem, Ilan PhD ABPP is an Associate Professor in the Department of Psychiatry at Yale University School of Medicine. For the past 17 years, he has been treating and investigating PTSD. Dr. Harpaz-Rotem has successfully obtained funding from NIH, DoD, VA and private organizations to assist him in successfully conducting his research, which includes broad range of topics such as PTSD treatment (psychological and pharmacological), PTSD symptom structure, risk and protective factors associated with PTSD and depression, translational neuroscience, and neurobiology of traumatic stress and resilience.
Dr. Harpaz-Rotem has a strong interest in the relationship between the phenotypic expression of PTSD symptoms, its potential neurobiological underpinnings, and potential resiliency or risk factors. Exposure to trauma and its sequelae are associated with the phenotypic expression of a wide range of psychiatric symptoms, particularly those implicated in acute threat (i.e., fear), potential threat (i.e., anxiety), and sustained threat arousal and regulatory systems (i.e., dysphoric and anxious arousal); and loss (i.e., anhedonia). This investigation of the phenotypic expression of stress-related psychopathology is closely related to the National Institute of Mental Health Research Domain Criteria (RDoC) project. To further enhance his work, Dr. Harpaz-Rotem collaborates with leading neuroscientists in the field of computational neuroscience (Drs. Levy and Schiller).
In additional to his research, Dr. Harpaz-Rotem serves as an attending clinical psychologist at the mental health clinic at the VACHS and in this capacity he has directed the outpatient psychological services at the West Haven VA Hospital. The proposed project above combines Dr. Harpaz-Rotem’s experience in the treatment and the neurobiology of PTSD.
Amount needed for the next phase of the project:
$50,000 to support direct research costs associated with this study.
Harpaz-Rotem, Ilan PhD ABPP
For the past 17 years, he has been treating and investigating PTSD. Dr. Harpaz-Rotem has successfully obtained funding from NIH, DoD, VA and private o...Read More...
“We are shedding new light on how people learn fear and unlearn it,”