Ketamine as a Rapid Treatment for Post-Traumatic Stress Disorder

PUBLIC ABSTRACT

A substantial number of Operation Iraqi Freedom veterans are expected to develop post-traumatic stress disorder (PTSD). PTSD is a debilitating anxiety disorder characterized by intrusive re-experiences of the traumatic events, avoidance of situations and stimuli that could serve as reminders of these events, and feeling jumpy or easily startled. Patients with PTSD are often also depressed, and many have significant memory impairments. Existing drug treatments are unsuccessful in a majority of patients, especially in those with combat-related PTSD. Our aim is to test the effectiveness of a potential new drug for PTSD, ketamine. For many years, intravenous ketamine has been extensively used for anesthesia. More recently, using doses lower than those used in anesthesia, a single ketamine infusion was shown to rapidly reduce depressed mood as well as anxiety in patients with severe depression. Some clinical evidence of potential efficacy in depressed patients with co-morbid PTSD also exists. Adverse effects in these studies have been limited to feeling intoxicated and having increased blood pressure during the infusion. In the present study, we expect a single ketamine infusion to reduce core PTSD symptoms. In addition, in those patients with PTSD who are depressed, we expect ketamine to reduce depressed mood. Finally, ketamine is known to impair memory function. We will also test if the extent of ketamine-induced memory impairment during the infusion can predict how well people do after the infusion. Forty patients with PTSD (with and without combat-related trauma histories) will be tested, using a design that will compare the effectiveness of intravenous ketamine to that of midazolam, another anesthetic drug without any known long-term effects on anxiety, depressed mood, and memory function. If ketamine is found to have the expected effects, future studies may explore additional benefits of repeated infusions and/or alternatives to intravenous drug administration. Our study may contribute to improved function of patients with PTSD by providing a new means to rapidly treat their debilitating symptoms.