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Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial)

BACKGROUND: Major depressive disorder is a common debilitating illness that is the second leading contributor to the global burden of disease. Unfortunately, about 30 % of patients do not respond to adequate trials of antidepressants and/or psychotherapies. About 45–60 % of such treatment-resistant...

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Autores principales: Finnegan, Martha, Ryan, Karen, Shanahan, Enda, Harkin, Andrew, Daly, Leslie, McLoughlin, Declan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153900/
https://www.ncbi.nlm.nih.gov/pubmed/27965856
http://dx.doi.org/10.1186/s40814-016-0080-0
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author Finnegan, Martha
Ryan, Karen
Shanahan, Enda
Harkin, Andrew
Daly, Leslie
McLoughlin, Declan M.
author_facet Finnegan, Martha
Ryan, Karen
Shanahan, Enda
Harkin, Andrew
Daly, Leslie
McLoughlin, Declan M.
author_sort Finnegan, Martha
collection PubMed
description BACKGROUND: Major depressive disorder is a common debilitating illness that is the second leading contributor to the global burden of disease. Unfortunately, about 30 % of patients do not respond to adequate trials of antidepressants and/or psychotherapies. About 45–60 % of such treatment-resistant patients will remit with electroconvulsive therapy (ECT). However, relapse rates are high following ECT—38 % after 6 months. There is a need for better relapse prevention strategies. One possibility is to use ketamine, a competitive glutamate receptor antagonist used for anaesthesia. A recent paradigm shift in treating depression and understanding its biology has been the finding that ketamine has a robust, rapid-onset, though short-lived, antidepressant effect that is possibly mediated through neuroplastic effects. However, ketamine has not previously been reported on for relapse prevention. METHODS/DESIGN: The main objective of this study is to conduct a randomised controlled pilot trial (n = 40) of a 4-week course of once-weekly ketamine infusions for relapse prevention following ECT for depression to assess trial procedures that will inform a future definitive trial. Participants with unipolar depression will be recruited prior to commencing ECT and be assessed weekly during the ECT course using the primary clinical outcome, the 24-item Hamilton Rating Scale for Depression (HRSD-24). Those who meet standard response criteria will be invited, on completing ECT, to be randomised in a 1:1 ratio to a course of four once-weekly infusions of ketamine or an active comparator midazolam, which mimics some of the effects of ketamine and may improve blinding over inactive placebo. Participants will be followed up over 6 months using the HRSD-24 to assess for relapse. DISCUSSION: This is the first registered trial (NCT02414932, https://clinicaltrials.gov/ct2/show/NCT02414932) of ketamine for depression relapse prevention, an important possible use of this agent. The primary focus of the pilot trial is on feasibility. However, a 95 % confidence interval will be determined for the difference between ketamine and midazolam groups in 6-month relapse rates to help inform a future definitive trial. TRIAL REGISTRATION: https://clinicaltrials.gov/ NCT02414932 Secondary Identifying numbers: EudraCT number: 2014-000339-18 Sponsors’ Reference, Sponsor: St. Patrick’s Mental Health Services: 05/14 Research Ethics Committee Reference, Joint REC of St James’ and Tallaght Hospitals, Dublin: 2014-08-19 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40814-016-0080-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-51539002016-12-13 Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial) Finnegan, Martha Ryan, Karen Shanahan, Enda Harkin, Andrew Daly, Leslie McLoughlin, Declan M. Pilot Feasibility Stud Study Protocol BACKGROUND: Major depressive disorder is a common debilitating illness that is the second leading contributor to the global burden of disease. Unfortunately, about 30 % of patients do not respond to adequate trials of antidepressants and/or psychotherapies. About 45–60 % of such treatment-resistant patients will remit with electroconvulsive therapy (ECT). However, relapse rates are high following ECT—38 % after 6 months. There is a need for better relapse prevention strategies. One possibility is to use ketamine, a competitive glutamate receptor antagonist used for anaesthesia. A recent paradigm shift in treating depression and understanding its biology has been the finding that ketamine has a robust, rapid-onset, though short-lived, antidepressant effect that is possibly mediated through neuroplastic effects. However, ketamine has not previously been reported on for relapse prevention. METHODS/DESIGN: The main objective of this study is to conduct a randomised controlled pilot trial (n = 40) of a 4-week course of once-weekly ketamine infusions for relapse prevention following ECT for depression to assess trial procedures that will inform a future definitive trial. Participants with unipolar depression will be recruited prior to commencing ECT and be assessed weekly during the ECT course using the primary clinical outcome, the 24-item Hamilton Rating Scale for Depression (HRSD-24). Those who meet standard response criteria will be invited, on completing ECT, to be randomised in a 1:1 ratio to a course of four once-weekly infusions of ketamine or an active comparator midazolam, which mimics some of the effects of ketamine and may improve blinding over inactive placebo. Participants will be followed up over 6 months using the HRSD-24 to assess for relapse. DISCUSSION: This is the first registered trial (NCT02414932, https://clinicaltrials.gov/ct2/show/NCT02414932) of ketamine for depression relapse prevention, an important possible use of this agent. The primary focus of the pilot trial is on feasibility. However, a 95 % confidence interval will be determined for the difference between ketamine and midazolam groups in 6-month relapse rates to help inform a future definitive trial. TRIAL REGISTRATION: https://clinicaltrials.gov/ NCT02414932 Secondary Identifying numbers: EudraCT number: 2014-000339-18 Sponsors’ Reference, Sponsor: St. Patrick’s Mental Health Services: 05/14 Research Ethics Committee Reference, Joint REC of St James’ and Tallaght Hospitals, Dublin: 2014-08-19 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40814-016-0080-0) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-03 /pmc/articles/PMC5153900/ /pubmed/27965856 http://dx.doi.org/10.1186/s40814-016-0080-0 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Study Protocol
Finnegan, Martha
Ryan, Karen
Shanahan, Enda
Harkin, Andrew
Daly, Leslie
McLoughlin, Declan M.
Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial)
title Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial)
title_full Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial)
title_fullStr Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial)
title_full_unstemmed Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial)
title_short Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial)
title_sort ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the keep-well trial)
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153900/
https://www.ncbi.nlm.nih.gov/pubmed/27965856
http://dx.doi.org/10.1186/s40814-016-0080-0
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