Effects of the NMDA receptor antagonist ketamine on stress hormone system regulation, cognitive functioning and posttraumatic stress symptomatology in accident victims

We previously demonstrated a strong association between the administration of a single dose of the analgesic ketamine and symptoms of acute (Schönenberg M et al, J Psychopharmacol 2007; in press) and posttraumatic stress disorder (Schönenberg M et al, Psychopharmacology 2005; 182: 420–425) in accident victims. The purpose of the present, ongoing study is to replicate and extend previous findings in a prospective study design. Endocrine stress parameters and changes in cognitive functioning are assessed in order to elucidate the underlying mechanism of ketamines' action on PTSD symptomatology. Accident victims who had received a single or fractionated dose of either ketamine (n=20), or opioids (n=17) during initial emergency care, as well as 21 healthy volunteers were investigated so far. Initial assessments of posttraumatic psychopathology were carried out within 48 hrs post-event and were repeated two months post-event. Further, neuropsychological assessments and a diurnal profile of the biological stress markers cortisol and dehydroepiandrosterone (DHEA) were determined at each time point. Analyses revealed elevated morning cortisol in ketamine patients. Ketamine subjects also showed more pronounced cognitive impairment, and strongly increased posttraumatic symptomatology. Our preliminary results suggest a profound modulating influence of a single sub-anaesthetic dose ketamine on endocrine, neuropsychological, and psychopathological stress parameters in accident victims.