Ketamine effects on EEG and their links to therapy differ across treatment-resistant major depression, post-traumatic stress disorder, and obsessive-compulsive disorder.

INTRODUCTION

Neurotic disorders-major depressive disorder (MDD), panic disorder, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and specific phobia-have differing pharmaceutical profiles. But all, even when resistant to conventional treatment (TR), respond quickly to low-dose (0.5-1.0 mg/kg I.M.) ketamine. We explore the variation in the neural effects of ketamine across its treatments of TR-MDD, TR-PTSD, and TR-OCD.

MATERIALS AND

METHODS

We recorded 10 min of resting frontal activity and diagnosis-related scale measures, before and 2 h after fentanyl (50 mcg) or ketamine (0.5 or 1.0 mg/kg, I.M.) counterbalanced across 3 sessions at least a week apart. Average power spectra were calculated for delta, theta, alpha1, alpha2, beta, and gamma bands. Analysis of variance compared TR-PTSD (20 F, 2 M) with TR-MDD (12 F, 13 M). Preliminary TR-OCD (5 F, 2 M) data were also obtained.

RESULTS

TR-PTSD patients showed dose- and band frequency-dependent electroencephalography (EEG) power changes (particularly alpha at 0.05 mg/kg), while TR-MDD patients did not. TR-OCD differed qualitatively from both. The correlation of power change with score change was maximal for different bands and electrodes across the different scales (Impact of Events Scale-Revised, Montgomery-Åsberg Depression Rating Scale, Hospital Anxiety and Depression Scales, Hamilton Anxiety Scale, Fear Questionnaire, and Yale-Brown Obsessive-Compulsive Scale).

DISCUSSION: Ketamine effects and their therapeutic links vary in band and site with conventional diagnosis-including previous TR anxiety results. The EEG results appear to detect changes in the disorder-specific systems that conventional treatments target selectively and directly and these appear to require a ketamine-sensitive factor (as a "double hit") to generate disorder.