Exploring Clinical Subgroups of Participants with Major Depressive Disorder that May Benefit from Adjunctive Minocycline Treatment
Gerard Anmella1,2,3,4,5, Alcy Meehan6, Melanie Ashton6, Mohammadreza Mohebbi6,7, Giovanna Fico1,2,3,4,5, Chee H. Ng8, Michael Maes6,9, Lesley Berk6, Michele De Prisco1,2,3,4,5, Ajeet B. Singh6, Gin S. Malhi10,11,12, Michael Berk6,13,14,15, Seetal Dodd6,13,14, Diego Hidalgo-Mazzei1,2,3,4,5, Iria Grande1,2,3,4,5, Isabella Pacchiarotti1,2,3,4,5, Andrea Murru1,2,3,4,5, Eduard Vieta1,2,3,4,5, Olivia M. Dean6,15
1Department of Psychiatry and Psychology, Institute of Neuroscience, Hospital Clínic de Barcelona, Barcelona, Catalonia, Spain
2Bipolar and Depressive Disorders Unit, Digital Innovation Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
3Biomedical Research Networking Centre Consortium on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
4Department of Medicine, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Spain
5Institute of Neurosciences (UBNeuro), Barcelona, Spain
6Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, VIC, Australia
7Deakin University, Faculty of Health, Biostatistics Unit, Geelong, VIC, Australia
8The Melbourne Clinic, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia
9Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand
10Department of Psychiatry, Northern Clinical School, The University of Sydney, Faculty of Medicine and Health, Sydney, NSW, Australia
11Academic Department of Psychiatry, Northern Clinical School, The University of Sydney, Sydney, NSW, Australia
12CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, Sydney, NSW, Australia
13Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia
14Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia
15Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
Correspondence to: Olivia M. Dean
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, HERB B Level 3, P.O. Box 281, Geelong 3220, Australia
E-mail: o.dean@deakin.edu.au
ORCID: https://orcid.org/0000-0002-2776-3935
Received: May 24, 2023; Revised: July 5, 2023; Accepted: July 6, 2023; Published online: August 28, 2023.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Objective: To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT).
Methods: This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-weeks) using ANCOVA.
Results: There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects.
Conclusion: Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications.
Keywords: Minocycline; Depression; Treatment; Clinical trial; Theragnostic; Inflammation

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