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

Ketamine at low doses (0.5-1.0 mg/kg I.M.) quickly reduces symptoms in treatment-resistant major depressive disorder (TR-MDD), post-traumatic stress disorder (TR-PTSD), and obsessive-compulsive disorder (TR-OCD), but its neural effects differ by diagnosis. EEG recordings of resting frontal activity before and after ketamine or fentanyl showed that TR-PTSD patients had dose- and band-frequency-dependent power changes (especially alpha at 0.5 mg/kg), while TR-MDD patients showed no such changes. TR-OCD responses differed qualitatively from both. Correlations between EEG power changes and symptom scale improvements varied by band and electrode across different disorder-specific scales. Ketamine's effects and their therapeutic links vary by brain site and frequency band depending on the DSM diagnosis, suggesting disorder-specific systems require a ketamine-sensitive factor to generate the disorder.

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.