Ketamine aggravates symptoms of acute stress disorder in a naturalistic sample of accident victims

Abstract

The glutamatergic N-methyl-D-aspartate receptor antagonist ketamine produces transient dissociative states and alters cognitive functioning in healthy humans, thus resembling the core symptoms of acute and chronic post-traumatic stress disorder (PTSD). First evidence exists that the common use of the analgesic and sedative properties of ketamine during emergency care correlates with sustained symptoms of PTSD in accident victims. The aim of the present study was to examine whether ketamine administration after moderate accidental trauma modulates dissociation and other symptoms of acute stress disorder (ASD) in the direct aftermath of the event. Accident victims were screened within the third day after admission to hospital for symptoms of ASD (Peritraumatic Dissociative Experiences Questionnaire, ASD Scale) and prior stressful life events (Traumatic Life Events Questionnaire). Subjects had received a single or fractionated dose of either racemic ketamine (n=13), opioids (n=24) or non-opioid analgesics (n=13) during initial emergency treatment. There were no significant differences between medication groups in demographic and clinical characteristics such as injury severity or prior traumatization. With respect to ASD symptomatology three days post-event there were significant associations between ketamine analgosedation and increased symptoms of dissociation, reexperiencing, hyperarousal and avoidance relative to the comparison groups.Growing evidence exists that ketamine might modulate or aggravate early post-traumatic stress reactions when given in the acute trauma phase, which in turn might contribute to long-lasting symptomatology.

Effects of systemic glutamatergic manipulations on conditioned eyeblink responses and hyperarousal in a rabbit model of post-traumatic stress disorder

“…There have been mixed reports, for example, on the benefits of ketamine treatment received by traumatic accident and burn victims, with some reporting that it can decrease prevalence of PTSD (McGhee et al, 2008) while others report that it can increase the severity of PTSD diagnostic scores (Schonenberg et al, 2005, 2008; Winter and Irle, 2004). Tests of subanesthetic ketamine in healthy volunteers have reported dissociative and psychosis-like effects that mimic schizophrenia (Krystal et al, 1994; Morgan et al, 2004) as well as biomarkers of stress such as increased cortisol, impairment of stress-sensitive memory function, and transient changes in the activity of the hypothalamic pituitary adrenal axis revealed by brain imaging (Khalili-Mahani et al, 2015).…”

Post-traumatic stress disorder: new directions in pharmacotherapy

“…Further work by Schönenberg et al (2008) found that ketamine aggravated PTSD in burns victims, producing early acute stress disorder, dissociative states, re-experiencing, hyper arousal and avoid ance behaviours. The study looked at patients who had received a dose of either ketamine (n = 13), opioids (n = 24) or non-opioid analgesics (n = 13) during initial emergency treatment.…”

Nonconventional interventions for chronic post-traumatic stress disorder: Ketamine, repetitive trans-cranial magnetic stimulation (rTMS), and alternative approaches

“…Two retrospective studies (Strayer & Nelson, 2008;Schönenberg, Reichwald, Domes, Badke, & Hautzinger, 2008) claim that ketamine may possibly exacerbate symptoms of PTSD. However, retrospective design in both of these studies is an A c c e p t e d M a n u s c r i p t 14 important methodological limitation.…”