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

Summary

Ketamine treatment shows varying neural effects across different neurotic disorders, with TR-PTSD patients experiencing significant EEG power changes, particularly in the alpha band, while TR-MDD patients did not exhibit such changes. The study involved measuring resting frontal activity and various rating scales before and after administering ketamine or fentanyl. Results suggest that ketamine's effects are influenced by the specific disorder being treated, indicating a need for a ketamine-sensitive factor for therapeutic efficacy.

Study at a glance

Abstract

BACKGROUND: 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. AIMS: We explore the variation in the neural effects of ketamine across its treatments of TR-MDD, TR-PTSD and TR-OCD. METHODS: We recorded 10-minutes of resting frontal activity, and diagnosis-related scale measures, before and 2 hours after fentanyl (50mcg) or ketamine (0.5 or 1.0 mg/kg, I.M.) counterbalanced across three sessions at least a week apart. Average power spectra were calculated for delta, theta, alpha1, alpha2, beta and gamma bands. ANOVA compared TR-PTSD (20F, 2M) with TR-MDD (12F, 13M). Preliminary TR-OCD (5F, 2M) data were also obtained. RESULTS: TR-PTSD patients showed dose- and band frequency-dependent 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). CONCLUSIONS: Ketamine effects and their therapeutic links vary in band and site with DSM 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. FUNDING: Funding for this study was provided by Health Research Council New Zealand project grant HRC 20-112; the HRCNZ had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

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