Combining the antibiotic minocycline with antidepressants gave greater improvement in depressive symptoms in patients with treatment-resistant depression and low-grade peripheral inflammation, according to a new UK study published in Neuropsychopharmacology.
Researchers conducted a four-week, placebo-controlled, randomised clinical trial of minocycline (200 mg/day) added to antidepressant treatment in 39 patients selected for elevated levels of serum C-reactive protein (CRP ≥1 mg/L); randomised to minocycline (M; n=18) and to placebo (P; n=21).
The main outcome was the change in Hamilton Depression Rating Scale (HAM-D-17) score from baseline to week 4 in the overall sample and after further stratification for baseline CRP ≥3 mg/L. Secondary outcomes included changes in other clinical and inflammatory measures.
After stratification for CRP levels <3 mg/L (CRP−) or ≥3 mg/L (CRP+), CRP+/M patients showed the largest changes in HAM-D-17 scores (mean±SD, 12.00±6.45) compared with CRP−/M (2.42±3.20; P<.001), CRP+/P (3.50±4.34; P=.003) and CRP−/P (2.11±3.26, P=.006) patients, and the largest proportion (83.3%; P=.04) of partial treatment response at week 4.
The threshold for baseline CRP to distinguish responders from non-responders to minocycline was 2.8 mg/L.
Responders to minocycline also had higher baseline IL-6 concentrations than non-responders (P=.03); IFNγ was significantly reduced after treatment with minocycline compared with placebo (P=.03).
Study author Dr Valeria Mondelli said: "Of the many patients with depression who do not respond to usual antidepressant treatment, we have shown in previous studies that in at least two thirds of patients this could be due to the increased levels of inflammation. Now, with this study, we are identifying a potential new effective treatment for these patients."
"Although replications in larger samples are needed, we believe our study has a potentially important clinical impact, as we moved a step towards the identification of personalized treatments for Major depressive disorder (MDD).”
