Minocycline as adjuvant not superior to placebo in reducing symptoms in patients with resistant depression

A study was conducted to determine whether 6 weeks of minocycline as an add-on to antidepressant treatment, as usual, can significantly reduce depressive symptoms in patients with Treatment-Resistant Depression.

The study was conducted in Germany and designed as a multicenter double-blind randomized clinical trial (RCT) of 200 mg/d minocycline treatment over a course of 6 weeks with a 6-month follow-up. Participants were recruited from January 2016 to August 2020 at 9 university hospitals that served as study sites. Key inclusion criteria were a diagnosis of major depressive disorder (according to Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] criteria), the severity of depressive symptoms on the Hamilton Depression Rating Scale (HAMD-17) greater than or equal to 16 points, aged 18 to 75 years, body mass index 18 to 40, Clinical Global Impression Scale (CGI-S) greater than or equal to 4, failure to adequately respond to an initial antidepressant standard medication as per Massachusetts General Hospital Antidepressant Treatment History Questionnaire, and stable medication for at least 2 weeks. A total of 258 patients were screened, of whom 173 were randomized and 168 were included in the intention-to-treat population. Statistical analysis was performed from April to November 2020.

Results:

• Of 173 eligible and randomized participants 168 formed the intention-to-treat sample with 81 in the minocycline group and 87 in the placebo group.
• The mean (SD) age was 46.1 (13.1) years, and the mean (SD) MADRS score at baseline was 26.5 (5.0). There was no difference in rates of completion between the minocycline and the placebo group
• Minocycline treatment did not alter the course of depression severity compared with placebo as assessed by a decrease in MADRS scores over 6 weeks of treatment
• Minocycline treatment also exhibited no statistically significant effect on secondary outcomes.

In this large randomized clinical trial with minocycline at a dose of 200 mg/d added to antidepressant treatment as usual for 6 weeks, minocycline was well tolerated but not superior to placebo in reducing depressive symptoms in patients with TRD. The results of this RCT emphasize the unmet need for therapeutic approaches and predictive biomarkers in TRD.

Reference:

Hellmann-Regen J, Clemens V, Grözinger M, et al. Effect of Minocycline on Depressive Symptoms in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Netw Open. 2022;5(9):e2230367. doi:10.1001/jamanetworkopen.2022.30367

Keywords:

Hellmann-Regen J, Clemens V, Grözinger M, Effect, Minocycline, Depressive, Symptoms, Patients Treatment-Resistant, Depression, Randomized, Clinical Trial, JAMA Netw Open, Psychiatry