title: Minocycline and celecoxib as adjunctive treatments for bipolar depression: a study protocol for a multicenter factorial design randomized controlled trial.
abstract: BACKGROUND
  Evidence suggests that the use of anti-inflammatory agents may improve depressive symptoms in patients with bipolar affective disorder. However, there are few well-designed clinical trials demonstrating the efficacy of these newer treatment strategies.
  
  
  METHODS
  This is a multicenter, 3-month, randomized, placebo-controlled, double-blind, factorial design trial of minocycline and/or celecoxib added to TAU for the treatment of depressive symptoms in patients experiencing a DSM-5 bipolar I or II disorder and a current major depressive episode. A total of 240 participants will undergo screening and randomization followed by four assessment visits. The primary outcome measure will be mean change from baseline to week 12 on the Hamilton Depression Scale scores. Clinical assessments using the Clinical Global Impression scale, Patient Health Questionnaire-9, and the Generalized Anxiety Disorder 7-item scale will be carried out at every visit as secondary outcomes. Side-effect checklists will be used to monitor the adverse events at each visit. Complete blood count and plasma C-reactive protein will be measured at baseline and at the end of the treatment. Minocycline will be started at 100 mg once daily and increased to 200 mg at 2 weeks. Celecoxib will be started at 200 mg once daily and increased to 400 mg at 2 weeks.
  
  
  CONCLUSIONS
  Anti-inflammatory agents have been shown to be potentially efficacious in the treatment of depressive symptoms. The aim of this study is to determine whether the addition of minocycline and/or celecoxib to TAU improves depressive symptoms in patients with bipolar affective disorder.
authors.affiliation: Camden and Islington NHS Foundation Trust, St Pancras Hospital, London, UK.
authors.forename: Muhammad I
authors.initials: MI
authors.lastname: Husain
authors.affiliation: Pakistan Institute of Learning and Living.
authors.forename: Imran B
authors.initials: IB
authors.lastname: Chaudhry
authors.affiliation: Department of Psychiatry, Abbasi Shaheed Hospital, Karachi.
authors.forename: Munir M
authors.initials: MM
authors.lastname: Hamirani
authors.affiliation: Institute of Psychiatry, Rawalpindi Medical College, Rawalpindi.
authors.forename: Fareed A
authors.initials: FA
authors.lastname: Minhas
authors.affiliation: Department of Psychiatry, Karwan-e-Hayat Hospital, Karachi, Pakistan.
authors.forename: Ajmal
authors.initials: A
authors.lastname: Kazmi
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London.
authors.forename: John
authors.initials: J
authors.lastname: Hodsoll
authors.affiliation: Division of Psychology and Mental Health, University of Manchester, Manchester.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Haddad
authors.affiliation: Division of Psychology and Mental Health, University of Manchester, Manchester.
authors.forename: John Fw
authors.initials: JF
authors.lastname: Deakin
authors.affiliation: Division of Psychology and Mental Health, University of Manchester, Manchester.
authors.forename: Nusrat
authors.initials: N
authors.lastname: Husain
authors.affiliation: Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Allan H
authors.initials: AH
authors.lastname: Young
keywords: anti-inflammatory; bipolar disorder; celecoxib; depression; inflammation; minocycline