Cargando…

Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety

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 generalize...

Descripción completa

Detalles Bibliográficos
Autores principales: Shadli, Shabah Mohammad, Kawe, Tame, Martin, Daniel, McNaughton, Neil, Neehoff, Shona, Glue, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070106/
https://www.ncbi.nlm.nih.gov/pubmed/29718262
http://dx.doi.org/10.1093/ijnp/pyy032
_version_ 1783343621585502208
author Shadli, Shabah Mohammad
Kawe, Tame
Martin, Daniel
McNaughton, Neil
Neehoff, Shona
Glue, Paul
author_facet Shadli, Shabah Mohammad
Kawe, Tame
Martin, Daniel
McNaughton, Neil
Neehoff, Shona
Glue, Paul
author_sort Shadli, Shabah Mohammad
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6070106
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-60701062018-08-09 Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety Shadli, Shabah Mohammad Kawe, Tame Martin, Daniel McNaughton, Neil Neehoff, Shona Glue, Paul Int J Neuropsychopharmacol Regular Research Articles 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. Oxford University Press 2018-04-24 /pmc/articles/PMC6070106/ /pubmed/29718262 http://dx.doi.org/10.1093/ijnp/pyy032 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of CINP. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Regular Research Articles
Shadli, Shabah Mohammad
Kawe, Tame
Martin, Daniel
McNaughton, Neil
Neehoff, Shona
Glue, Paul
Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety
title Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety
title_full Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety
title_fullStr Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety
title_full_unstemmed Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety
title_short Ketamine Effects on EEG during Therapy of Treatment-Resistant Generalized Anxiety and Social Anxiety
title_sort ketamine effects on eeg during therapy of treatment-resistant generalized anxiety and social anxiety
topic Regular Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070106/
https://www.ncbi.nlm.nih.gov/pubmed/29718262
http://dx.doi.org/10.1093/ijnp/pyy032
work_keys_str_mv AT shadlishabahmohammad ketamineeffectsoneegduringtherapyoftreatmentresistantgeneralizedanxietyandsocialanxiety
AT kawetame ketamineeffectsoneegduringtherapyoftreatmentresistantgeneralizedanxietyandsocialanxiety
AT martindaniel ketamineeffectsoneegduringtherapyoftreatmentresistantgeneralizedanxietyandsocialanxiety
AT mcnaughtonneil ketamineeffectsoneegduringtherapyoftreatmentresistantgeneralizedanxietyandsocialanxiety
AT neehoffshona ketamineeffectsoneegduringtherapyoftreatmentresistantgeneralizedanxietyandsocialanxiety
AT gluepaul ketamineeffectsoneegduringtherapyoftreatmentresistantgeneralizedanxietyandsocialanxiety