title: Minocycline as an adjunct for treatment-resistant depressive symptoms: study protocol for a pilot randomised controlled trial.
abstract: BACKGROUND
  Depression is one of the leading causes of disability worldwide. A high proportion of patients do not respond to standard drug treatments. Recent evidence has suggested that anti-inflammatory treatment may have beneficial effects in major depression. Minocycline is a tetracycline antibiotic with good CNS penetration that exerts effects on multiple interacting symptoms implicated in the pathophysiology of mood disorders. Open-label studies have suggested that minocycline is effective as an adjunct drug in improving depressive symptoms.
  
  
  METHODS
  This is a multi-centre, 3-month, double-blind, placebo-controlled, pilot trial of minocycline added to treatment as usual for patients suffering from DSM-IV major depressive disorder. This will be a double-blind, randomised, controlled, two parallel-arm study with 20 participants in each arm, giving a total of 40 participants. There will be a screening visit, a randomization visit and four follow-up visits. Clinical assessments using the Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ -9) and the Generalised Anxiety Disorder scale (GAD-7) will be carried out at every visit. Side effects checklists will also be undertaken at each visit. Biomarkers (inflammatory cytokines and CRP) will be measured at baseline and at the end of the treatment phase. Minocycline will be started at 100 mg once daily (OD) and will be increased to 200 mg at two weeks.
  
  
  CONCLUSIONS
  Anti-inflammatory treatments have been shown to have some beneficial effects in the treatment of major depressive disorder. The aim of this pilot randomised controlled trial is to establish the degree of improvement in depressive symptoms with the addition of minocycline to treatment as usual.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02263872 registered 10 October 2014.
authors.affiliation: Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK. ishrat-h@doctors.net.uk.
authors.forename: Muhammad I
authors.initials: MI
authors.lastname: Husain
authors.affiliation: The Mount, Whalley Road, Accrington, Lanacashire, BB5 5DE, UK. imran.chaudhry@manchester.ac.uk.
authors.forename: Imran B
authors.initials: IB
authors.lastname: Chaudhry
authors.affiliation: Dow Institute of Health Sciences, Karachi, Pakistan. razaur@yahoo.com.
authors.forename: Raza R
authors.initials: RR
authors.lastname: Rahman
authors.affiliation: Department of Psychiatry, Abbasi Shaheed Hospital, Karachi, Pakistan. mhamirani@gmail.com.
authors.forename: Munir M
authors.initials: MM
authors.lastname: Hamirani
authors.affiliation: Ashworth Research Centre, Mersey Care NHS Trust, Parkbourn, Maghull, L51 1HW, UK. inti.qurashi@merseycare.nhs.uk.
authors.forename: Inti
authors.initials: I
authors.lastname: Qurashi
authors.affiliation: Pakistan Institute of Learning and Living, Karachi, Pakistan. ameerbuxkhoso@gmail.com.
authors.forename: Ameer B
authors.initials: AB
authors.lastname: Khoso
authors.affiliation: University of Manchester, Oxford Road, Manchester, UK. bill.deakin@manchester.ac.uk.
authors.forename: John F W
authors.initials: JF
authors.lastname: Deakin
authors.affiliation: University of Manchester, Oxford Road, Manchester, UK. nusrat.husain@manchester.ac.uk.
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, De Crespigny Park, London, SE5 8AF, UK. allan.young@kcl.ac.uk.
authors.forename: Allan H
authors.initials: AH
authors.lastname: Young
mesh_terms: D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D061218:Depressive Disorder, Treatment-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D008911:Minocycline / Q000009:adverse effects / Q000627:therapeutic use*; D010154:Pakistan; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D008911:Minocycline