Psychological Medicine

Original Articles

Subanesthetic dose of ketamine decreases prefrontal theta cordance in healthy volunteers: implications for antidepressant effect

J. Horaceka1a2a3 c1, M. Brunovskya1a2, T. Novaka2, B. Tislerovaa3, T. Paleniceka2a3, V. Bubenikova-Valesovaa1a2, F. Spaniela1a3, J. Koprivovaa2a3, P. Mohra1, M. Balikovaa4 and C. Hoschla1a2a3

a1 Prague Psychiatric Centre, Prague, Czech Republic

a2 Centre of Neuropsychiatric Studies, Prague, Czech Republic

a3 Third Medical Faculty of Charles University, Prague, Czech Republic

a4 Institute of Forensic Medicine and Toxicology, First Medical Faculty, Charles University, Prague, Czech Republic


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.

(Received January 27 2008)

(Revised September 03 2009)

(Accepted September 28 2009)

(Online publication December 09 2009)


c1 Address for correspondence: Prof. Dr J. Horacek, Ph.D., Prague Psychiatric Centre, Ustavni 91, 181 03 Prague 8, Czech Republic. (Email: