Olivia M Dean1,2,3, Buranee Kanchanatawan4, Melanie Ashton1,2,5, Mohammadreza Mohebbi1, Chee Hong Ng5, Michael Maes4, Lesley Berk1,6, Atapol Sughondhabirom4, Sookjaroen Tangwongchai4, Ajeet B Singh1, Helen McKenzie1, Deidre J Smith5, Gin S Malhi7,8, Nathan Dowling5, Michael Berk1,2,3,9,10. 1. 1 IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia. 2. 2 The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia. 3. 3 Department of Psychiatry, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia. 4. 4 Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 5. 5 Department of Psychiatry, The Melbourne Clinic, The University of Melbourne, Richmond, VIC, Australia. 6. 6 School of Psychology, Faculty of Health, Deakin University, Geelong, VIC, Australia. 7. 7 Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. 8. 8 CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, St. Leonards, NSW, Australia. 9. 9 Orygen Youth Health Research Centre, Parkville, VIC, Australia. 10. 10 Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.
Abstract
OBJECTIVE: Conventional antidepressant treatments result in symptom remission in 30% of those treated for major depressive disorder, raising the need for effective adjunctive therapies. Inflammation has an established role in the pathophysiology of major depressive disorder, and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth. This double-blind, randomised, placebo-controlled trial examined adjunctive minocycline (200 mg/day, in addition to treatment as usual) for major depressive disorder. This double-blind, randomised, placebo-controlled trial investigated 200 mg/day adjunctive minocycline (in addition to treatment as usual) for major depressive disorder. METHODS: A total of 71 adults with major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) were randomised to this 12-week trial. Outcome measures included the Montgomery-Asberg Depression Rating Scale (primary outcome), Clinical Global Impression-Improvement and Clinical Global Impression-Severity, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool. The study was registered on the Australian and New Zealand Clinical Trials Register: www.anzctr.org.au , #ACTRN12612000283875. RESULTS: Based on mixed-methods repeated measures analysis of variance at week 12, there was no significant difference in Montgomery-Asberg Depression Rating Scale scores between groups. However, there were significant differences, favouring the minocycline group at week 12 for Clinical Global Impression-Improvement score - effect size (95% confidence interval) = -0.62 [-1.8, -0.3], p = 0.02; Quality of Life Enjoyment and Satisfaction Questionnaire score - effect size (confidence interval) = -0.12 [0.0, 0.2], p < 0.001; and Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool score - 0.79 [-4.5, -1.4], p < 0.001. These effects remained at follow-up (week 16), and Patient Global Impression also became significant, effect size (confidence interval) = 0.57 [-1.7, -0.4], p = 0.017. CONCLUSION: While the primary outcome was not significant, the improvements in other comprehensive clinical measures suggest that minocycline may be a useful adjunct to improve global experience, functioning and quality of life in people with major depressive disorder. Further studies are warranted to confirm the potential of this accessible agent to optimise treatment outcomes.
RCT Entities:
OBJECTIVE: Conventional antidepressant treatments result in symptom remission in 30% of those treated for major depressive disorder, raising the need for effective adjunctive therapies. Inflammation has an established role in the pathophysiology of major depressive disorder, and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth. This double-blind, randomised, placebo-controlled trial examined adjunctive minocycline (200 mg/day, in addition to treatment as usual) for major depressive disorder. This double-blind, randomised, placebo-controlled trial investigated 200 mg/day adjunctive minocycline (in addition to treatment as usual) for major depressive disorder. METHODS: A total of 71 adults with major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) were randomised to this 12-week trial. Outcome measures included the Montgomery-Asberg Depression Rating Scale (primary outcome), Clinical Global Impression-Improvement and Clinical Global Impression-Severity, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool. The study was registered on the Australian and New Zealand Clinical Trials Register: www.anzctr.org.au , #ACTRN12612000283875. RESULTS: Based on mixed-methods repeated measures analysis of variance at week 12, there was no significant difference in Montgomery-Asberg Depression Rating Scale scores between groups. However, there were significant differences, favouring the minocycline group at week 12 for Clinical Global Impression-Improvement score - effect size (95% confidence interval) = -0.62 [-1.8, -0.3], p = 0.02; Quality of Life Enjoyment and Satisfaction Questionnaire score - effect size (confidence interval) = -0.12 [0.0, 0.2], p < 0.001; and Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool score - 0.79 [-4.5, -1.4], p < 0.001. These effects remained at follow-up (week 16), and Patient Global Impression also became significant, effect size (confidence interval) = 0.57 [-1.7, -0.4], p = 0.017. CONCLUSION: While the primary outcome was not significant, the improvements in other comprehensive clinical measures suggest that minocycline may be a useful adjunct to improve global experience, functioning and quality of life in people with major depressive disorder. Further studies are warranted to confirm the potential of this accessible agent to optimise treatment outcomes.
Authors: Matthew G Frank; Laura K Fonken; Samuel D Dolzani; Jessica L Annis; Philip H Siebler; Dominic Schmidt; Linda R Watkins; Steven F Maier; Christopher A Lowry Journal: Brain Behav Immun Date: 2018-05-26 Impact factor: 7.217
Authors: Gouri J Mahajan; Eric J Vallender; Michael R Garrett; Lavanya Challagundla; James C Overholser; George Jurjus; Lesa Dieter; Maryam Syed; Damian G Romero; Hamed Benghuzzi; Craig A Stockmeier Journal: Prog Neuropsychopharmacol Biol Psychiatry Date: 2017-11-22 Impact factor: 5.067