Journal of psychopharmacology (Oxford, England)Sep 1, 2017

Minocycline added to treatment for hard-to-treat depression: A small controlled trial

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Updated Apr 2, 2026

Abstract

A large decrease in depressive symptoms was observed with minocycline treatment, showing a standardized effect size of -1.21 (p < 0.001).

Minocycline was added to usual treatment in patients with treatment-resistant depression over a 12-week period.
The minocycline group experienced significant improvements in Hamilton Depression Rating Scale (HAMD-17) scores compared to the placebo group.
Clinical Global Impression (CGI) scores indicated a large improvement in the minocycline group, with an odds ratio of 17.6 (p < 0.001).
Moderate improvements were observed in secondary measures, including the Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder scale (GAD-7), and EuroQoL (EQ-5D).
Results suggest that adjunctive minocycline may improve symptoms in patients who have not responded to at least two antidepressants.

Simplified

BACKGROUND: Evidence suggests that anti-inflammatory medication may be effective in the treatment of depressive symptoms. In this study, we aimed to investigate whether minocycline added to treatment as usual (TAU) for 3 months in patients with treatment-resistant depression will lead to an improvement in depressive symptoms.

METHODS: Multi-site, 12-week, double-blind, placebo-controlled, pilot trial of minocycline added to TAU for patients suffering from DSM-5 major depressive disorder, whose current episode has failed to respond to at least two antidepressants. The primary outcome measure was mean change in Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 12. Secondary measures were the Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder scale (GAD-7) and EuroQoL (EQ-5D) quality-of-life questionnaire. Side-effect checklists were also used. Minocycline was started at 100 mg once daily (OD) and increased to 200 mg after 2 weeks.

RESULTS: A total of 41 participants were randomised, with 21 in the minocycline group and 20 in the placebo group. A large decrease in HAMD scores was observed in the minocycline group compared to the placebo group (standardised effect size (ES) -1.21, p < 0.001). CGI scores in the minocycline group also showed a large improvement compared with placebo (odds ratio (OR): 17.6, p < 0.001). PHQ-9, GAD-7 and EQ-5D total showed more moderate improvements (ES ~ 0.4-0.5).

CONCLUSION: The findings indicate that adjunctive minocycline leads to improvement in symptoms of treatment-resistant depression. However, our findings require replication in a larger sample.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02263872, registered October 2014.

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Minocycline added to treatment for hard-to-treat depression: A small controlled trial

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