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

Abstract

BackgroundDepression 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/DesignThis 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.DiscussionAnti-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 registrationClinicalTrials.gov NCT02263872 registered 10 October 2014.

Role of Inflammation in Suicide: From Mechanisms to Treatment

“…Preliminary data from an open-label study of patients with MDD suggest that adjunctive minocycline treatment is able to reduce the severity of depressive and psychotic symptoms (Miyaoka et al, 2012). Currently, ongoing RCTs are investigating the effect of minocycline add-on treatment for the management of depressive symptoms in patients with treatment-resistant depression (Husain et al, 2015), MDD (Dean et al, 2014), and bipolar depression (Savitz et al, 2012).…”

Mood by microbe: towards clinical translation

“…Alternatively, the elimination of certain microbes using selective antimicrobial agents may have a positive mental health benefit in some individuals. Preclinical studies and initial patient-based studies indicate the potential of the antibiotic minocycline as an antidepressant [ 10 ]. Minocycline impacts on both Gram-positive and Gram-negative bacteria, although it also exerts an influence on immune mechanisms.…”

Neuroinflammation—a co-occurring phenomenon linking chronic pain and opioid dependence

“…Thus, glial activation in the mesocorticolimbic system is a common pathophysiology triggering the genesis of depression in both chronic pain and opioid dependence. Indeed, inhibitors of neuroinflammation (including the tetracycline microglial inhibitor minocycline) were shown to be effective adjunct therapy in major depressive disorders [65] and improved the affective dimension of chronic neuropathic pain without altering its intensity [66 • ]. …”