1.
Ketamine aggravates symptoms of acute stress disorder in a naturalistic sample of accident victims.
Schönenberg, M, Reichwald, U, Domes, G, Badke, A, Hautzinger, M
Journal of psychopharmacology (Oxford, England). 2008;(5):493-7
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.
2.
Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects.
Krystal, JH, Abi-Saab, W, Perry, E, D'Souza, DC, Liu, N, Gueorguieva, R, McDougall, L, Hunsberger, T, Belger, A, Levine, L, et al
Psychopharmacology. 2005;(1):303-9
Abstract
RATIONALE Some of the behavioral consequences of deficits in N-methyl-D-aspartate (NMDA) glutamate receptor function are thought to arise from the disinhibition of cortical glutamatergic circuitry. OBJECTIVE This study evaluated whether pretreatment with a drug that reduces glutamatergic activation, the group II metabotropic glutamate receptor (mGluR) agonist, LY354740, reduced the cognitive effects of the NMDA glutamate receptor antagonist, ketamine, in healthy human subjects. METHODS Nineteen healthy human subjects completed 3 test days during which LY354740 (matched placebo, 100 mg, 400 mg) was administered under double-blind conditions 4 h prior to the single-blind intravenous administration of saline and 5.7 h prior to ketamine administration (bolus of 0.26 mg/kg over 1 min, infusion of 0.65 mg/kg per hour for 100 min). Thus on each test day each subject received a single dose of LY354740 (or its matched placebo) and both saline and ketamine infusions. RESULTS Ketamine impaired attention, working memory, and delayed recall. It also produced positive and negative symptoms, perceptual changes, and dysphoric mood. LY354740 did not have a significant effect on working memory on the placebo day; however, it produced a significant dose-related improvement in working memory during ketamine infusion. CONCLUSIONS These data provide preliminary and suggestive evidence that LY354740 or other group II mGluR agonists might play a role in treating working memory impairment related to deficits in NMDA receptor function.