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Add-on Minocycline No Better Than Placebo for Treatment-Resistant Depression
Although it was well-tolerated, the antibiotic minocycline added to standard antidepressant medication for 6 weeks failed to reduce depressive symptoms in patients with treatment-resistant major depressive disorder (MDD) compared with placebo, according to study results published online in JAMA Network Open.
“The failure of minocycline treatment to reduce depressive symptoms in a naturalistic sample of patients with treatment-resistant depression is a setback for anti-inflammatory treatment strategies in this clinical population,” researchers wrote, “given the suggestive evidence for advantageous effects of minocycline from prior, albeit considerably smaller, trials.”
Related: Vortioxetine Enhances Functioning in Real-World Outpatients with MDD
The double-blind randomized clinical trial included 168 patients with treatment-resistant major depressive disorder at 9 university hospitals in Germany. Among participants, 94.6% were White, nearly half were women, the average age was 46.1 years, and the mean Montgomery-Åsberg Depression Rating Scale (MADRS) score at baseline was 26.5. Participants received 200 mg of minocycline treatment or placebo daily over 6 weeks.
Depression severity—as measured by change from baseline MADRS score—was not significantly better with minocycline compared with placebo at 6 weeks. Researchers reported mean MADRS score reductions of 8.46 points in the minocycline group and 8.01 points in the placebo group.
Secondary outcome measures that looked at response, remission, and other clinical rating scales showed no statistically significant advantage with add-on minocycline. Minocycline was well-tolerated, however, with discontinuation rates and adverse events similar to placebo.
“While prior research had suggested that anti-inflammatory approaches may be more efficient in patients with increased inflammatory markers, we purposely sought to recruit a naturalistic population of treatment-resistant depression, assuming elevated baseline inflammation as a potentially underlying cause in at least a subgroup of the recruited patients,” researchers wrote.
"Interestingly, post hoc stratification for baseline C-reactive protein levels did not yield any results supporting a hypothesis of minocycline treatment possibly being more effective in participants exhibiting higher-grade baseline inflammation.”
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