Clin Psychopharmacol Neurosci.  2014 Dec;12(3):180-188. 10.9758/cpn.2014.12.3.180.

Protocol and Rationale-The Efficacy of Minocycline as an Adjunctive Treatment for Major Depressive Disorder: A Double Blind, Randomised, Placebo Controlled Trial

  • 1Innovations in Mental and Physical Health and Clinical Treatments Strategic Research Centre, Deakin University, School of Medicine, Geelong, Australia.
  • 2Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
  • 3Department of Psychiatry, University of Melbourne, Parkville, Australia.
  • 4Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand.
  • 5Centre for Mental Health and Wellbeing Research, Deakin University, School of Psychology, Burwood, Australia.
  • 6Department of Psychiatry, University of Melbourne, The Melbourne Clinic, Richmond, Australia.
  • 7Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, Australia.
  • 8Department of Psychiatry, CADE Clinic, St. Leonards, Australia.
  • 9Orygen Youth Health Research Centre, Parkville, Australia.
  • 10Centre of Youth Mental Health, University of Melbourne, Parkville, Australia.


While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of 'antidepressant' but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression.


Minocycline; Depression; Clinical research protocol; Inflammation; Oxidative stress
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