Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial) [version 2; peer review: 2 approved]
Background: Depression is a common psychiatric disorder that has become the leading cause of disability worldwide. The standard medical care for depression over the past 50 years has focused on monoamine neurotransmitters. These treatments can take weeks to take effect, highlighting the need for nov...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2022-01-01
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| Series: | HRB Open Research |
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| Online Access: | https://hrbopenresearch.org/articles/3-90/v2 |
| _version_ | 1819121357191905280 |
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| author | Meabh Foley Bronagh Gallagher Gabriele Gusciute Claire M. Slattery Declan M. McLoughlin Enda Shanahan |
| author_facet | Meabh Foley Bronagh Gallagher Gabriele Gusciute Claire M. Slattery Declan M. McLoughlin Enda Shanahan |
| author_sort | Meabh Foley |
| collection | DOAJ |
| description | Background: Depression is a common psychiatric disorder that has become the leading cause of disability worldwide. The standard medical care for depression over the past 50 years has focused on monoamine neurotransmitters. These treatments can take weeks to take effect, highlighting the need for novel treatment strategies. One such approach may be ketamine. Ketamine acts as an antagonist of the N-methyl-D-asparate receptor and thus targets the excitatory amino acid neurotransmitter glutamate. Interestingly, at sub-anaesthetic doses, a single infusion of ketamine can elicit a rapid, though transient, antidepressant response. Methods: The aim of this study was to conduct a pragmatic randomised controlled pilot trial of four once-weekly ketamine infusions as an adjunctive therapy for depression. The main objective was to assess trial procedures to inform a future definitive trial. The primary clinical outcome was the 24-item Hamilton Rating Scale for Depression (HRSD-24). Trial participants were patients admitted to St Patrick’s Mental Health Services for treatment of a depressive episode. They underwent usual inpatient care as prescribed by their treating team. Consented participants were randomly allocated to a four-week course of either once-weekly ketamine (0.5mg/kg) or midazolam (0.045mg/kg) infusions given over 40 minutes and with 12 weeks follow-up. Results: In total, 1581 admissions to St Patrick’s Hospital were assessed for eligibility over nine months, with 125 (8%) meeting criteria, with 25 (20%) providing consent. In total, 13 were randomly assigned to the ketamine arm and 12 to the midazolam arm. There were no major differences in HRSD-24 scores between the two groups. The infusions were generally safe and well tolerated. Conclusions: This is the first pragmatic pilot trial of adjunctive serial ketamine infusions for hospitalised depression, an important possible use of ketamine. This study suggests that a definitive trial of adjunctive ketamine is feasible. Trial registration: ClinicalTrials.gov NCT03256162 21/08/2017; EudraCT 2016-004764-18 30/11/2016. |
| first_indexed | 2024-12-22T06:35:16Z |
| format | Article |
| id | doaj.art-ffea4f915f294451a92ad0d805506834 |
| institution | Directory Open Access Journal |
| issn | 2515-4826 |
| language | English |
| last_indexed | 2024-12-22T06:35:16Z |
| publishDate | 2022-01-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | HRB Open Research |
| spelling | doaj.art-ffea4f915f294451a92ad0d8055068342022-12-21T18:35:36ZengF1000 Research LtdHRB Open Research2515-48262022-01-01314714Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial) [version 2; peer review: 2 approved]Meabh Foley0Bronagh Gallagher1https://orcid.org/0000-0001-9941-0904Gabriele Gusciute2Claire M. Slattery3Declan M. McLoughlin4https://orcid.org/0000-0003-4574-2799Enda Shanahan5Department of Psychiatry, Trinity College Dublin, St. Patrick’s University Hospital, James Street, Dublin, IrelandDepartment of Psychiatry, Trinity College Dublin, St. Patrick’s University Hospital, James Street, Dublin, IrelandDepartment of Psychiatry, Trinity College Dublin, St. Patrick’s University Hospital, James Street, Dublin, IrelandDepartment of Psychiatry, Trinity College Dublin, St. Patrick’s University Hospital, James Street, Dublin, IrelandDepartment of Psychiatry, Trinity College Dublin, St. Patrick’s University Hospital, James Street, Dublin, IrelandDepartment of Psychiatry, Trinity College Dublin, St. Patrick’s University Hospital, James Street, Dublin, IrelandBackground: Depression is a common psychiatric disorder that has become the leading cause of disability worldwide. The standard medical care for depression over the past 50 years has focused on monoamine neurotransmitters. These treatments can take weeks to take effect, highlighting the need for novel treatment strategies. One such approach may be ketamine. Ketamine acts as an antagonist of the N-methyl-D-asparate receptor and thus targets the excitatory amino acid neurotransmitter glutamate. Interestingly, at sub-anaesthetic doses, a single infusion of ketamine can elicit a rapid, though transient, antidepressant response. Methods: The aim of this study was to conduct a pragmatic randomised controlled pilot trial of four once-weekly ketamine infusions as an adjunctive therapy for depression. The main objective was to assess trial procedures to inform a future definitive trial. The primary clinical outcome was the 24-item Hamilton Rating Scale for Depression (HRSD-24). Trial participants were patients admitted to St Patrick’s Mental Health Services for treatment of a depressive episode. They underwent usual inpatient care as prescribed by their treating team. Consented participants were randomly allocated to a four-week course of either once-weekly ketamine (0.5mg/kg) or midazolam (0.045mg/kg) infusions given over 40 minutes and with 12 weeks follow-up. Results: In total, 1581 admissions to St Patrick’s Hospital were assessed for eligibility over nine months, with 125 (8%) meeting criteria, with 25 (20%) providing consent. In total, 13 were randomly assigned to the ketamine arm and 12 to the midazolam arm. There were no major differences in HRSD-24 scores between the two groups. The infusions were generally safe and well tolerated. Conclusions: This is the first pragmatic pilot trial of adjunctive serial ketamine infusions for hospitalised depression, an important possible use of ketamine. This study suggests that a definitive trial of adjunctive ketamine is feasible. Trial registration: ClinicalTrials.gov NCT03256162 21/08/2017; EudraCT 2016-004764-18 30/11/2016.https://hrbopenresearch.org/articles/3-90/v2Ketamine Depression Adjunctive Pilot trialeng |
| spellingShingle | Meabh Foley Bronagh Gallagher Gabriele Gusciute Claire M. Slattery Declan M. McLoughlin Enda Shanahan Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial) [version 2; peer review: 2 approved] HRB Open Research Ketamine Depression Adjunctive Pilot trial eng |
| title | Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial) [version 2; peer review: 2 approved] |
| title_full | Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial) [version 2; peer review: 2 approved] |
| title_fullStr | Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial) [version 2; peer review: 2 approved] |
| title_full_unstemmed | Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial) [version 2; peer review: 2 approved] |
| title_short | Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial) [version 2; peer review: 2 approved] |
| title_sort | ketamine as an adjunctive therapy for major depression a randomised controlled pragmatic pilot trial karma dep trial version 2 peer review 2 approved |
| topic | Ketamine Depression Adjunctive Pilot trial eng |
| url | https://hrbopenresearch.org/articles/3-90/v2 |
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