Minocycline as adjunctive treatment for major depressive disorder: Pooled data from two randomized controlled trials

Abstract

Background: Randomized controlled clinical trials that have investigated minocycline as an adjunctive treatment for major depressive disorder have proved promising. Data from two studies were pooled to evaluate more definitively whether the addition of minocycline to standard treatment for major depressive disorder leads to an improvement of depressive symptoms when compared with placebo. Methods: Both studies were multi-site, double-blinded, placebo-controlled trials of minocycline 200 mg/day added to treatment as usual during a 12-week period. The primary outcome measure was change in depressive symptoms (Montgomery–Asberg Depression Rating Scale in Dean et al. and Hamilton Depression Rating Scale in Husain et al.). Secondary outcomes were change in depression severity (Montgomery–Asberg Depression Rating Scale for Dean et al. and 9-item Patient Health Questionnaire in Husain et al.), anxiety severity (Hamilton Anxiety Rating Scale in Dean et al. and Generalized Anxiety Disorder 7-item scale in Husain et al.) and functional status, which were also evaluated as potential mediators on the primary outcome. Results: A total of 112 participants were included in the pooled data (Dean et al., n = 71; Husain et al., n = 41). A significant change from baseline to week 12 was noted in depressive symptoms – differential change (Placebo vs Minocycline): 9.0, 95% confidence interval = [4.2, 13.9], Cohen’s D (95% confidence interval): 0.71 [0.29, 1.14], p < 0.001 – anxiety severity – differential change (Placebo vs Minocycline): 0.38, confidence interval = [0.00, 0.75], Cohen’s D (95% confidence interval): 0.41 [0.00, 0.82], p = 0.050) and functional status – differential change (Placebo vs Minocycline): 1.0, 95% confidence interval = [0.4, 1.5], Cohen’s D (95% confidence interval): 0.76 [0.34, 1.19], p = 0.001). Duration of illness, current use of benzodiazepine and pain medication were identified as moderators, whereas functional status as a mediator/predictor. Conclusion: The improvement of depressive symptoms, anxiety severity and functional status is promising and suggests that minocycline has potential as an adjunctive treatment for major depressive disorder. However, further studies are warranted to confirm therapeutic effects of minocycline in major depressive disorder. Trial registrations: NCT02263872, registered October 2014, and ACTRN12612000283875, registered March 2012.

Antibiotics and mental health: The good, the bad and the ugly

“…More recently, Zazula et al. [ 50 ] pooled the data from two studies and reached similar conclusions. However, Husain et al.…”

“…In a subgroup of patients who had psychotic depression, Miyaoka et al also found efficacy when the antibiotic was administered as an adjunctive therapy [49]. More recently, Zazula et al [50] pooled the data from two studies and reached similar conclusions. However, Husain et al found no evidence of minocycline efficacy in bipolar depression [51].…”

Succinum extracts inhibit microglial-derived neuroinflammation and depressive-like behaviors

“…As expected, PSE exerted pharmacological effects on sickness, anxiety, and depressive-like behaviors as well as inhibitory effect on microglial over-activation in hippocampal CA3 region ( Figures 5A–F ). Pooled data for two RCTs recently showed that minocycline, a specific microglial inhibitor, improved depressive symptoms and reduced the severity of anxiety in a total of 112 participants with major depressive disorders ( Zazula et al, 2021 ). However, there is concern about other risks of using minocycline to treat anxiety and depression because it is also an antibiotic ( Schmidt et al, 2021 ).…”

Novel Pharmacological Approaches to the Treatment of Depression

“…Infliximab, a TNF-α antagonist, inhibited TNF receptor (TNFR)/nuclear factor κB (NF-κB) signaling and depressive symptoms in MDD patients who were exposed to early life stress [218]. Minocycline is a tetracycline antibiotic that mediated neuroprotective effects and alleviated depressive symptoms by modulating CRP_and IL-6 [219][220][221]. Medications used to treat inflammatory conditions, such as psoriasis, (guselkumab [222] and ustekinumab [223]), rheumatoid arthritis (etanercept [224] and tocilizumab [225]), hidradenitis suppurativa (adalimumab [226]) also improved depressive symptoms in these patients.…”