A pilot, open‐label, 8‐week study evaluating the efficacy, safety and tolerability of adjunctive minocycline for the treatment of bipolar I/II depression
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ObjectivesThe objectives of the study were to determine if adjunctive minocycline mitigates depressive symptom severity and improves cognitive function in individuals with bipolar I/II disorder (BD). The study also aimed to determine if changes in depressive and/or cognitive symptoms over the course of treatment were associated with changes in circulating inflammatory cytokine levels.MethodsA total of 29 (intention‐to‐treat: n=27) adults meeting DSM‐IV‐TR criteria for a major depressive episode as part of bipolar I or II disorder (i.e. Hamilton Depression Rating Scale 17‐item [HAMD‐17] ≥20) were enrolled in an 8‐week, open‐label study with adjunctive minocycline (100 mg bid). The primary outcome measure was the Montgomery−Åsberg Depression Rating Scale (MADRS). The HAMD‐17, Clinical Global Impression‐Severity (CGI‐S), cognitive test composite scores and plasma cytokines were secondary outcome measures. Plasma cytokines were measured with the 30 V‐Plex Immunoassay from Meso Scale Discovery.ResultsAdjunctive minocycline was associated with a reduction in depressive symptom severity from baseline to week 8 on the MADRS (P<.001, d=0.835), HAMD‐17 (P<.001, d=0.949) and CGI‐S (P<.001, d=1.09). Improvement in psychomotor speed, but not verbal memory or executive function, was observed only amongst individuals exhibiting a reduction in depression severity (P=.007, d=0.826). Levels of interleukin (IL)‐12/23p40 (P=.002) were increased, while levels of IL‐12p70 (P=.001) and C‐C motif chemokine ligand 26 (CCL26) (P<.001) were reduced from baseline to week 8. A reduction in CCL26 levels was associated with a less favourable treatment response (P<.001).ConclusionsResults from the pilot study suggest that adjunctive minocycline may exert antidepressant effects in individuals with bipolar depression, possibly by targeting inflammatory cytokines.
