Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial).
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Authors
Finnegan, Martha
Ryan, Karen
Shanahan, Enda
Harkin, Andrew
Daly, Leslie
McLoughlin, Declan M
Issue Date
2016-08-03
Type
Journal Article
Language
en
Keywords
Depression , Electroconvulsive therapy , Ketamine , Pilot trial , Relapse prevention
Alternative Title
Abstract
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.
The main objective of this study is to conduct a randomised controlled pilot trial ( = 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.
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.
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.
The main objective of this study is to conduct a randomised controlled pilot trial ( = 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.
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.
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.
Description
Citation
Finnegan, M., Ryan, K., Shanahan, E., Harkin, A., Daly, L., & McLoughlin, D. M. (2016). Ketamine for depression relapse prevention following electroconvulsive therapy: protocol for a randomised pilot trial (the KEEP-WELL trial). Pilot and feasibility studies, 2, 38. https://doi.org/10.1186/s40814-016-0080-0
Publisher
License
Journal
Pilot and feasibility studies
Volume
2
Issue
PubMed ID
DOI
10.1186/s40814-016-0080-0
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10.1159/000351671
10.1177/0004867413486842
10.1186/1741-7015-8-18
10.1001/archpsyc.62.6.593
10.1016/j.euroneuro.2011.07.018
10.1016/S0140-6736(12)61729-2
10.1176/ajp.2006.163.11.1905
10.1016/S0140-6736(03)12705-5
10.1176/ajp.2007.164.1.73
10.1176/appi.ajp.2015.15030372
10.1016/j.biopsych.2010.06.009
10.1038/npp.2013.149
10.1016/S0140-6736(03)12599-8
10.1001/jama.285.10.1299
10.1017/S0033291714001603
10.1176/appi.ajp.2013.13030392
10.1016/j.psychres.2015.10.032
10.1007/s00213-014-3664-5
10.1002/jps.2600710516
10.1017/S1461145714001011
10.1007/s00213-013-3255-x
10.1016/j.jpsychires.2015.01.003
10.1016/j.biopsych.2009.08.038
10.1136/jnnp.23.1.56
10.1016/S0006-3223(02)01866-8
10.4088/JCP.08m04728
10.1016/0028-3932(71)90067-4
10.1023/A:1024465317902
10.2466/pr0.1962.10.3.799
10.1192/bjp.133.5.429
10.1097/00131746-200603000-00002
10.1159/000351671
10.1177/0004867413486842
10.1186/1741-7015-8-18
ISSN
2055-5784