Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2)

Muhammad Ishrat Husain, Clare Cullen, Madeha Umer, Andre F Carvalho, Stefan Kloiber, Jeffrey H Meyer, Abigail Ortiz, Yuliya Knyahnytska, M Omair Husain, Justine Giddens, Breno S Diniz, Wei Wang, Allan H Young, Benoit H Mulsant, Zafiris J Daskalakis, Muhammad Ishrat Husain, Clare Cullen, Madeha Umer, Andre F Carvalho, Stefan Kloiber, Jeffrey H Meyer, Abigail Ortiz, Yuliya Knyahnytska, M Omair Husain, Justine Giddens, Breno S Diniz, Wei Wang, Allan H Young, Benoit H Mulsant, Zafiris J Daskalakis

Abstract

Background: Available evidence suggests that adjunctive treatment with immunomodulatory medications may be effective in the treatment of major depressive disorder (MDD). A pilot trial of the tetracycline minocycline as adjunctive treatment in treatment-resistant depression (TRD), produced promising results, however, a larger scale trial is needed to confirm the antidepressant actions of this drug.

Methods: This is a 12-week double blind, placebo-controlled, randomized trial of minocycline as an add-on to standard antidepressants for adults (age > 18) with DSM-5 major depressive episode, who have failed to respond to at least two adequate trials of antidepressant treatment. It is a parallel-arm study with 50 participants in each group. The primary outcome measure is change in 17-item Hamilton Depression Rating Scale (HRSD-17) total scores from baseline to week 12. Secondary measures include the Clinical Global Impression (CGI) scale, World Health Organization Quality of Life Short Version (WHOQOL-BREF) and the Generalized Anxiety Disorder scale (GAD-7). Peripheral inflammatory biomarkers will be collected at baseline, week 6 and 12.

Discussion: If minocycline is well tolerated and effective in reducing depressive symptoms in patients with TRD, it would warrant genuine consideration as a treatment option for TRD. Additionally, if results demonstrate that minocycline has antidepressant properties, and that changes in inflammatory status are associated with its antidepressant action, it will inform the development of individualized treatment for a subset of patients with MDD.

Trial registration: Clinicaltrials.gov identifier: NCT03947827. Registered 13th May, 2019.

Keywords: Anti-inflammatory; Clinical trial; Depression; Inflammation; Minocycline.

Conflict of interest statement

MIH is a PI for a trial sponsored by COMPASS Pathways Limited. MIH was previously a trustee of the Pakistan Institute of Learning and Living. MIH receives research support from the Brain and Behavior Research Foundation, the Physician’s Services Incorporated (PSI) Foundation and the University of Toronto. BSD receives research support from the NIH. BHM currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study funded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). Within the past five years he has also received research support (medications for NIH-funded clinical trials) from Bristol-Myers, Eli Lilly, and Pfizer. He directly own stocks of General Electric (less than $5,000). AHY has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. AHY has undertaken investigator-initiated studies funded by Astra Zeneca, Eli Lilly, Lundbeck and Wyeth.

Figures

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SPIRIT Flow Diagram

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