Prevention of N-methyl-D-aspartate (NMDA) Antagonist-induced Psychosis in Kids
Status:
Completed
Trial end date:
2007-10-01
Target enrollment:
Participant gender:
Summary
Ketamine, an FDA approved anesthetic agent, is becoming the sedative/analgesic of choice for
emergency sedation in children because it causes deep sedation with minimal respiratory
depression in comparison to other available agents. However, emergence reactions are an
important adverse effect of ketamine, characterized by transient changes in cognitive
function, dissociation and mild schizophrenia-like symptoms. These cognitive and behavioral
effects are dose-dependently induced by ketamine and other antagonists of the
N-methyl-D-aspartate (NMDA) glutamate receptor. NMDA receptor hypofunction can disinhibit
excitatory (cholinergic/glutamatergic) projections in key areas of the brain, and this has
been proposed to explain key features of schizophrenia. Several treatments that block
excessive excitatory transmitter release have also been shown to prevent cognitive and
behavioral effects of ketamine-induced NMDA receptor hypofunction in humans. Alpha-2
adrenergic agonists, which can presynaptically inhibit acetylcholine release, can prevent
mild ketamine-induced behavioral and cognitive symptoms in healthy human adults. However,
this prevention strategy has not been evaluated in children. Children currently receive
clinically-indicated treatment with the NMDA antagonist, ketamine, and this age group is an
important target for pharmacological strategies aimed at the prevention of schizophrenia.
This application proposes a double-blind, placebo-controlled, randomized trial to test the
safety and effectiveness of dexmedetomidine, an FDA approved alpha-2 adrenergic agonist, in
preventing ketamine-induced mental symptoms in children. Planned primary analyses will
evaluate effects of the hypothesized prevention treatment on clinical and cognitive variables
using analysis of variance (ANOVA). The proposed experiments are relevant to future
prevention trials for individuals at risk for schizophrenia, and to preventing adverse
effects of NMDA antagonist anesthetic agents (ketamine, nitrous oxide).
Phase:
Phase 4
Details
Lead Sponsor:
Washington University School of Medicine
Collaborator:
National Alliance for Research on Schizophrenia and Depression