A pilot, open-label, 8-week study evaluating the efficacy, safety and tolerability of adjunctive minocycline for the treatment of bipolar I/II depression
Affiliations
Affiliations
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
- Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
- Department of Psychiatry, Kuwait University, Kuwait City, Kuwait.
- Psychosocial Oncology Clinic, University Health Network, Toronto, ON, Canada.
- Department of Psychology, University of Toronto, Toronto, ON, Canada.
- Neuropsychology Clinic, University Health Network, Toronto, ON, Canada.
- Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil.
- Department of Psychiatry, Women's College Hospital, Toronto, ON, Canada.
- Department of Toxicology and Pharmacology, University of Toronto, Toronto, ON, Canada.
Abstract
Objectives: The 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.
Methods: A 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.
Results: Adjunctive 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).
Conclusions: Results from the pilot study suggest that adjunctive minocycline may exert antidepressant effects in individuals with bipolar depression, possibly by targeting inflammatory cytokines.
Keywords: bipolar disorder; clinical trial; cytokines; depression; inflammation; microglia; minocycline.
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