Minocycline as an adjunct for treatment-resistant depressive symptoms:study protocol for a pilot randomised controlled trial

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/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT02263872 registered 10 October 2014

Minocycline and celecoxib as adjunctive treatments for bipolar depression:a study protocol for a multicenter factorial design randomized controlled trial

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. / Patients and 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. / Discussion: 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