Michael Berk1,2,3,4,5,6, Mohammadreza Mohebbi7,8, Olivia M Dean7,9,10, Sue M Cotton11,12, Andrew M Chanen11,12,13, Seetal Dodd12,7,14,10, Aswin Ratheesh11,12,13, G Paul Amminger11,12, Mark Phelan11,12,13, Amber Weller11,12, Andrew Mackinnon15,16, Francesco Giorlando14,13, Shelley Baird11,12, Lisa Incerti11,12, Rachel E Brodie11,12, Natalie O Ferguson11,12, Simon Rice11,12,13, Miriam R Schäfer11,12, Edward Mullen11,12,13, Sarah Hetrick12,17, Melissa Kerr11,12, Susy M Harrigan16,18, Amelia L Quinn11,12, Catherine Mazza7, Patrick McGorry11,12, Christopher G Davey11,12,13. 1. Orygen, the National Centre of Excellence in Youth Mental Health, Melbourne, Australia. michael.berk@deakin.edu.au. 2. Centre for Youth Mental Health, University of Melbourne, Parkville, Australia. michael.berk@deakin.edu.au. 3. The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia. michael.berk@deakin.edu.au. 4. Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia. michael.berk@deakin.edu.au. 5. Department of Psychiatry, University of Melbourne, Parkville, Australia. michael.berk@deakin.edu.au. 6. Barwon Health, PO Box 281, Geelong, Victoria, 3220, Australia. michael.berk@deakin.edu.au. 7. The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia. 8. Biostatistics Unit, Faculty of Health, Deakin University, Geelong, Australia. 9. Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia. 10. Barwon Health, PO Box 281, Geelong, Victoria, 3220, Australia. 11. Orygen, the National Centre of Excellence in Youth Mental Health, Melbourne, Australia. 12. Centre for Youth Mental Health, University of Melbourne, Parkville, Australia. 13. Orygen Youth Health, Northwestern Mental Health, Melbourne, Australia. 14. Department of Psychiatry, University of Melbourne, Parkville, Australia. 15. Black Dog Institute, University of New South Wales, Sydney, Australia. 16. Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia. 17. Department of Psychological Medicine, University of Auckland, Auckland, New Zealand. 18. Department of Social Work, Monash University, Melbourne, Australia.
Abstract
BACKGROUND: Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15-25 years). METHODS: YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15-25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (- 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (- 4.2, 95% CI (- 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12. CONCLUSIONS: The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.
RCT Entities:
BACKGROUND:Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15-25 years). METHODS: YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15-25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (- 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (- 4.2, 95% CI (- 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12. CONCLUSIONS: The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.
Authors: Yara J Toenders; Liliana Laskaris; Christopher G Davey; Michael Berk; Yuri Milaneschi; Femke Lamers; Brenda W J H Penninx; Lianne Schmaal Journal: Mol Psychiatry Date: 2021-10-11 Impact factor: 15.992
Authors: Jonathan Savitz; Bart N Ford; Rayus Kuplicki; Sahib Khalsa; T Kent Teague; Martin P Paulus Journal: Psychopharmacology (Berl) Date: 2022-10-22 Impact factor: 4.415
Authors: Riccardo De Giorgi; Alice M G Quinton; Shona Waters; Philip J Cowen; Catherine J Harmer Journal: Psychopharmacology (Berl) Date: 2022-05-05 Impact factor: 4.415