A pilot study of minocycline for the treatment of bipolar depression: Effects on cortical glutathione and oxidative stress in vivo.

Background: The antibiotic minocycline appears to promote neuroprotection through antioxidant and other mechanisms that may be relevant to the pathophysiology of bipolar disorder. The present study assessed the efficacy of minocycline in bipolar depression and examined the association between minocycline treatment and brain glutathione (GSH), an essential regulator of oxidative stress.

Method: Twenty patients with bipolar disorder experiencing acute depressive symptoms enrolled in an 8-week, open-label trial of adjuvant minocycline. Depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and proton magnetic resonance spectroscopy (H MRS) measures of cortical GSH within a voxel prescribed in the precuneus and aspects of the occipital cortex were obtained from a subset of patients (n=12) before and after treatment.

Results: The daily dose of minocycline at study end was 256mg (SD: 71mg). Treatment was associated with improvements in depression severity [MADRS score change: -14.6 (95% CI: -7.8 to -21.3)]. Ten patients (50%) were classified as responders based on a ≥50% reduction in MADRS score and 8 patients (40%) were classified as remitters (MADRS score ≤ 9). Higher baseline GSH levels were associated with greater improvement in MADRS score following treatment (ρ=0.51, p=0.05). Increases in GSH levels at study end were higher in non-responders than in responders (p=0.04).

Limitations: Small sample size, lack of a placebo group.

Conclusion: Minocycline may be an effective adjuvant treatment for bipolar depression, particularly in patients with high baseline GSH levels. Further research is needed to evaluate the potential of minocycline in this population.