Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety
This randomised, double-blind, active placebo-controlled study (n=12) investigated the effects of 3 ascending ketamine dose levels (17.5/35/70mg/70kg) and midazolam (0.7mg/70kg) on electrophysiological brain activity in patients with anxiety. While ketamine increased high-frequency brain rhythms and decreased low-frequency rhythms in a dose-dependent manner, only decreases within the frontal theta frequency band were related to improvements in anxiety.
Authors
- Paul Glue
- Donel Martin
Published
Abstract
Background
Ketamine is swiftly effective in a range of neurotic disorders that are resistant to conventional antidepressant and anxiolytic drugs. The neural basis for its therapeutic action is unknown. Here we report the effects of ketamine on the EEG of patients with treatment-resistant generalized anxiety and social anxiety disorders.
Methods
Twelve patients with refractory DSM-IV generalized anxiety disorder and/or social anxiety disorder provided EEG during 10 minutes of relaxation before and 2 hours after receiving double-blind drug administration. Three ascending ketamine dose levels (0.25, 0.5, and 1 mg/kg) and midazolam (0.01 mg/kg) were given at 1-week intervals to each patient, with the midazolam counterbalanced in dosing position across patients. Anxiety was assessed pre- and postdose with the Fear Questionnaire and HAM-A.
Results
Ketamine dose-dependently improved Fear Questionnaire but not HAM-A scores, decreased EEG power most at low (delta) frequency, and increased it most at high (gamma) frequency. Only the decrease in medium-low (theta) frequency at right frontal sites predicted the effect of ketamine on the Fear Questionnaire. Ketamine produced no improvement in Higuchi’s fractal dimension at any dose or systematic changes in frontal alpha asymmetry.
Conclusions
Ketamine may achieve its effects on treatment-resistant generalized anxiety disorder and social anxiety disorder through related mechanisms to the common reduction by conventional anxiolytic drugs in right frontal theta. However, in the current study midazolam did not have such an effect, and it remains to be determined whether, unlike conventional anxiolytics, ketamine changes right frontal theta when it is effective in treatment-resistant depression.
Research Summary of 'Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety'
Introduction
Anxiety disorders such as generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are common, often persistent, and frequently resistant to conventional treatments; one-third of SAD patients, for example, remain treatment resistant, producing substantial impairment and economic burden. Ketamine, an NMDA receptor antagonist, has shown rapid efficacy across several treatment-resistant neurotic conditions including depression, obsessive–compulsive disorder, and post‑traumatic stress disorder, but the neural mechanisms underlying its anxiolytic effects remain unclear. Prior human and animal work has reported mixed effects of ketamine on EEG rhythms (reductions in delta, theta and alpha, with increases in gamma in some studies), and neuroimaging and pharmacological evidence implicates glutamatergic dysfunction in SAD; these observations motivated the current study. Shadli and colleagues set out to examine concurrent changes in anxiety symptoms and frontal EEG in treatment-refractory GAD and SAD patients after double‑blind administration of three ascending ketamine doses and an active control (midazolam). The primary aim was to test whether ketamine produces dose-related symptom improvements together with specific EEG changes, in particular alterations in frontal alpha asymmetry and Higuchi's fractal dimension, and band‑specific power shifts (decreases in delta/alpha/beta and increases in theta/gamma) that might relate to clinical response.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Shadli, S. M., Kawe, T., Martin, D., McNaughton, N., Neehoff, S., & Glue, P. (2018). Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety. International Journal of Neuropsychopharmacology, 21(8), 717-724. https://doi.org/10.1093/ijnp/pyy032
References (3)
Papers cited by this study that are also in Blossom
Glue, P., Medlicott, N. J., Harland, S. et al. · Journal of Psychopharmacology (2017)
Taylor, J. H., Landeros-Weisenberger, A., Coughlin, C. et al. · Neuropsychopharmacology (2017)
Zanos, P., Moaddel, P. J., Morris, P. J. et al. · Nature (2016)
Cited By (1)
Papers in Blossom that reference this study
Asim, M., Wang, B., Hao, B. et al. · Neurochemistry International (2021)
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