| Title: |
Serial ketamine infusions as adjunctive therapy to inpatient care for depression: the KARMA-Dep 2 randomized clinical trial |
| Authors: |
Jelovac, Ana; McCaffrey, Cathal; Terao, Masashi; Shanahan, Enda; Whooley, Emma; McDonagh, Kelly; McDonogh, Sarah; Loughran, Orlaith; Shackleton, Ellie; Igoe, Anna; Thompson, Sarah; Mohamed, Enas; Nguyen, Duyen; O'Neill, Ciaran; Walsh, Cathal; McLoughlin, Declan M. |
| Source: |
Jelovac, A, McCaffrey, C, Terao, M, Shanahan, E, Whooley, E, McDonagh, K, McDonogh, S, Loughran, O, Shackleton, E, Igoe, A, Thompson, S, Mohamed, E, Nguyen, D, O'Neill, C, Walsh, C & McLoughlin, D M 2025, 'Serial ketamine infusions as adjunctive therapy to inpatient care for depression: the KARMA-Dep 2 randomized clinical trial', JAMA Psychiatry, vol. 82, no. 12, pp. 1216-1224. https://doi.org/10.1001/jamapsychiatry.2025.3019 |
| Publication Year: |
2025 |
| Collection: |
Queen's University Belfast: Research Portal |
| Subject Terms: |
ketamine infusions; adjunctive therapy; depression |
| Description: |
Importance Serial ketamine infusions are being increasingly adopted as off-label treatment for major depression in routine clinical practice, yet robust psychoactive placebo-controlled trial evidence for short- and long-term efficacy and safety remains limited. Objective To assess antidepressant efficacy, safety, tolerability, cost-effectiveness, and quality of life during and after serial ketamine infusions compared with midazolam as an adjunct to usual inpatient care. Design, Setting, and Participants The KARMA-Dep 2 trial was an investigator-led, double-blind, randomized, midazolam-controlled, pragmatic trial conducted at an academic center in Ireland between September 2021 and August 2024. Participants included adults (≥18 years) hospitalized with a DSM-5 major depressive episode (unipolar or bipolar) and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥20. Interventions Participants were randomized 1:1 to receive up to 8 twice-weekly intravenous infusions of either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) as an adjunct to usual-care pharmacotherapy and other aspects of routine inpatient psychiatric care. Participants were followed up for 6 months. Main Outcomes and Measures The primary outcome was change in depression symptom severity measured by the observer-rated MADRS score from baseline to end of treatment. Secondary outcomes included self-reported depression severity, safety, tolerability, health care costs, and quality of life. Results Of 65 randomized participants (mean [SD] age, 53.5 [18.6] years; 37 [59.7%] male), 62 were included in the final analysis. In the analysis of primary outcome, end-of-treatment MADRS scores did not significantly differ between the ketamine and midazolam groups (adjusted mean difference, −3.16 points, 95% CI, −8.54 to 2.22; P = .25; Cohen d, −0.29). Similarly, there was no significant between-group difference between Quick Inventory of Depressive Symptoms, Self-Report, scores (adjusted mean difference, −0.002; 95% CI, −2.71 to 2.71; P > .99; ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2168-622X; 2168-6238 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pissn/2168-622X; info:eu-repo/semantics/altIdentifier/eissn/2168-6238 |
| DOI: |
10.1001/jamapsychiatry.2025.3019 |
| Availability: |
https://pure.qub.ac.uk/en/publications/4c34c426-fe1c-4bcc-ac7c-0e3518f614ee; https://doi.org/10.1001/jamapsychiatry.2025.3019; https://pureadmin.qub.ac.uk/ws/files/670038894/Serial_ketamine_infusions_as_adjunctive_therapy.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.F7426437 |
| Database: |
BASE |