Subanesthetic dose of ketamine decreases prefrontal theta cordance in healthy volunteers: implications for antidepressant effect
Jiřı́ Horáček, Martin Brunovský, Tomáš Novák, B. Tislerova, Tomáš Páleníček, Vĕra Bubeníková‐valešová, Filip Španiel, Jana Kopřivová, Pavel Mohr, Marie Balı́ková, Cyril Höschl
Psychological Medicine December 9, 2009 DOI: 10.1017/s0033291709991619 via OpenAlex
Summary
A single dose of ketamine (0.54 mg/kg infused over 30 minutes) rapidly alters brain electrical activity in healthy volunteers, producing a decrease in prefrontal theta cordance—a QEEG measure linked to cerebral blood flow—and an increase in central region theta cordance within 10 to 30 minutes. These changes resemble those seen after one week of treatment with standard antidepressants in people who respond to them, but occur much faster. The prefrontal theta cordance reduction correlated with ketamine and norketamine blood levels at 10 minutes. The findings suggest that theta cordance reduction could serve as a marker and predictor of ketamine's rapid antidepressant effect, a hypothesis warranting testing in depressed patients.
Study at a glance
| Characteristics | Double-blind, cross-over, placebo-controlled experiment Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy volunteers |
| Intervention | Ketamine |
| Dose | 0.54 mg/kg within 30 min |
| Topics | Ketamine |
| Keywords | Nmda receptor Antidepressant Psychology Placebo |
| Citations | 42 |
| Key finding | Ketamine infusion induces a decrease in prefrontal theta cordance and an increase in central region theta cordance within 10 to 30 minutes, changes similar to those that monoaminergic antidepressants induce gradually. |
Abstract
BACKGROUND: Theta cordance is a novel quantitative electroencephalography (QEEG) measure that correlates with cerebral perfusion. A series of clinical studies has demonstrated that the prefrontal theta cordance value decreases after 1 week of treatment in responders to antidepressants and that this effect precedes clinical improvement. Ketamine, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, has a unique rapid antidepressant effect but its influence on theta cordance is unknown. METHOD: In a double-blind, cross-over, placebo-controlled experiment we studied the acute effect of ketamine (0.54 mg/kg within 30 min) on theta cordance in a group of 20 healthy volunteers. RESULTS: Ketamine infusion induced a decrease in prefrontal theta cordance and an increase in the central region theta cordance after 10 and 30 min. The change in prefrontal theta cordance correlated with ketamine and norketamine blood levels after 10 min of ketamine infusion. CONCLUSIONS: Our data indicate that ketamine infusion immediately induces changes similar to those that monoamineric-based antidepressants induce gradually. The reduction in theta cordance could be a marker and a predictor of the fast-acting antidepressant effect of ketamine, a hypothesis that could be tested in depressive patients treated with ketamine.