Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety.
Shabah Mohammad Shadli, Tame Kawe, Daniel Martin, Neil McNaughton, Shona Neehoff, Paul Glue
The International Journal of Neuropsychopharmacology August 1, 2018 DOI: 10.1093/ijnp/pyy032 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind crossover dose-escalation study Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Patients with treatment-resistant DSM-IV generalized anxiety disorder and/or social anxiety disorder |
| Interventions | Ketamine Midazolam |
| Dose | 0.25, 0.5, and 1 mg/kg ketamine; 0.01 mg/kg midazolam |
| Duration | 1-week intervals between doses; EEG recorded before and 2 hours after each dose |
| Measures | Fear Questionnaire, HAM-A, EEG power (delta, theta, gamma), Higuchi's fractal dimension, frontal alpha asymmetry |
| Topics | Anxiety Ketamine Esketamine |
| Keywords | Electroencephalography Social anxiety disorder |
| Key points | Ketamine dose-dependently improved Fear Questionnaire scores but not HAM-A scores in patients with treatment-resistant generalized and/or social anxiety disorder. It decreased EEG power most at delta frequency and increased it most at gamma frequency, and only the decrease in right frontal theta predicted the Fear Questionnaire improvement. The authors propose that ketamine may act through mechanisms related to the reduction in right frontal theta produced by conventional anxiolytics, though midazolam did not show this effect in the current study. |
Abstract
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. 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. 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. 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.
Comparable studies
Other randomized controlled trials on ketamine for anxiety, most cited first.
Citations in the library
Cited by 12
- Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review BJPsych Open December 23, 2021
- An update on ketamine and its two enantiomers as rapid-acting antidepressants Expert Review of Neurotherapeutics December 4, 2018
- Ketamine-assisted psychotherapy for trauma-exposed patients in an outpatient setting: A clinical chart review study Journal of Psychedelic Studies October 1, 2021
- A randomized, placebo-controlled, cross-over trial of ketamine in Rett syndrome. Journal of neurodevelopmental disorders January 24, 2025
- A Comparison of the Anti-Anxiety Effects of Oral Ketamine and Fluvoxamine in Children with Separation Anxiety Disorder Manifesting as School Refusal Advanced Biomedical Research April 1, 2023
and 7 more in the library
Cites 10
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- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
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- Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Journal of Neuroscience August 19, 2015
and 5 more in the library