Journal
BIPOLAR DISORDERS
Volume 19, Issue 3, Pages 198-213Publisher
WILEY
DOI: 10.1111/bdi.12496
Keywords
bipolar disorder; clinical trial; cytokines; depression; inflammation; microglia; minocycline
Categories
Funding
- Mood Disorders Psychopharmacology Unit (MDPU)
- Canadian Biomarker Integration Network for Depression (CAN-BIND)
- Brain and Cognition Discovery Foundation (BCDF)
- Eli Lilly Canada Fellowship
- Ontario Graduate Scholarship
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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 (100mg bid). The primary outcome measure was the Montgomery-angstrom sberg 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 30V-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.
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