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Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial
  1. Jonathan Savitz1,2,
  2. Sheldon Preskorn3,
  3. T Kent Teague4,5,6,7,
  4. Douglas Drevets8,
  5. William Yates1,
  6. Wayne Drevets1,5
  1. 1Laureate Institute for Brain Research (LIBR), Tulsa, Oklahoma, USA
  2. 2Department of Medicine, Tulsa School of Community Medicine, University of Tulsa, Tulsa, Oklahoma, USA
  3. 3University of Kansas Clinical Research Institute, Wichita, Kansas, USA
  4. 4Department of Surgery, University of Oklahoma College of Medicine, Tulsa, Oklahoma, USA
  5. 5Department of Psychiatry, University of Oklahoma College of Medicine, Tulsa, Oklahoma, USA
  6. 6Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, Tulsa, Oklahoma, USA
  7. 7Department of Microbiology and Biochemistry, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, USA
  8. 8Department of Medicine, Oklahoma University Health Sciences Center, and the Oklahoma City VAMC, Oklahoma City, Oklahoma, USA
  1. Correspondence to Professor Wayne Drevets; wdrevets{at}laureateinstitute.org

Abstract

Introduction New medication classes are needed to improve treatment effectiveness in the depressed phase of bipolar disorder (BD). Extant evidence suggests that BD is characterised by neural changes such as dendritic remodelling and glial and neuronal cell loss. These changes have been hypothesised to result from chronic inflammation. The principal aims of the proposed research is to evaluate the antidepressant efficacy in bipolar depression of minocycline, a drug with neuroprotective and immune-modulating properties, and of aspirin, at doses expected to selectively inhibit cyclooxygenase 1 (COX-1).

Methods and analysis 120 outpatients between 18 and 55 years of age, who meet DSM-IV-TR criteria for BD (type I or II) and for a current major depressive episode will be recruited to take part in a randomised, double-blind, placebo-controlled, parallel-group, proof-of-concept clinical trial following a 2×2 design. As adjuncts to existing treatment, subjects will be randomised to receive one of the four treatment combinations: placebo-minocycline plus placebo-aspirin, active-minocycline plus placebo-aspirin, placebo-minocycline plus active-aspirin or active-minocycline plus active-aspirin. The dose of minocycline and aspirin is 100 mg twice daily and 81 mg twice daily, respectively. Antidepressant response will be evaluated by assessing changes in the Montgomery–Asberg Depression Rating Scale scores between baseline and the end of the 6-week trial. As secondary outcome measures, the anti-inflammatory effects of minocycline and aspirin will be tested by measuring pre-treatment and post-treatment levels of C reactive protein and inflammatory cytokines.

Ethics and dissemination Minocycline has been widely used as an antibiotic in doses up to 400 mg/day. Low-dose aspirin has been safely used on a worldwide scale for its role as an antithrombotic and thrombolytic. The study progress will be overseen by a Data, Safety and Monitoring Board, which will meet once every 6 months. Results of the study will be published in peer-reviewed publications.

Trial registration number Clinical Trials.gov: NCT01429272.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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Footnotes

  • To cite: Savitz J, Preskorn S, Teague TK, et al. Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial. BMJ Open 2012;2:e000643. doi:10.1136/bmjopen-2011-000643

  • Contributors All authors made a significant contribution to the conception and design of the study protocol. The protocol was written by JS and WD and was critically reviewed by SP, KT, DD and WY. All authors gave approval for the publication.

  • Funding This work was funded by the Stanley Medical Research Institute, grant number 10T-1401. The SMRI assisted with the study design but plays no role in the collection, management, analysis and interpretation of data; writing of the report or the decision to submit the report for publication.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by Western Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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