Abstract:~New medication classes are needed to improve treatment effectiveness in the depressed phase of bipolar disorder (BD). Extant evidence suggests that BD is not only characterized by reduced monoaminergic signaling, but also by neural changes such as dendritic remodeling, demyelination, and glial and neuronal cell loss. These changes have been hypothesized to result from chronic inflammation, based partly on convergent evidence that proinflammatory cytokines are elevated in depressed patients with BD. The principal aims of the proposed research is to evaluate the antidepressant efficacy in bipolar depression of minocycline, a drug with neuroprotective and immune-modulating properties, and of aspirin, at doses expected to selectively inhibit cyclooxygenase 1 (COX-1), within the context of a randomized, double-blind, placebo-controlled, parallel-group clinical trial following a 2 x 2 design.~Specific Aims Specific Aim 1: To evaluate the efficacy of augmentation therapy with minocycline and/or aspirin for bipolar depression.~The investigators will test the hypothesis that compared with placebo, participants receiving minocycline and/ or aspirin will show a greater treatment response rate (defined as a >50% increase on the MADRS for the final two consecutive visits).~Specific Aim 2: To investigate the relationship between the response to minocycline, aspirin and markers of inflammation (serum concentrations of IL-6 and CRP).~The investigators will test the hypotheses that: a) minocycline treatment will reduce inflammation to a greater extent than placebo; b) during minocycline treatment the change in inflammatory cytokine expression will correlate with the change in depression ratings; c) the baseline elevation of inflammatory markers will predict greater antidepressant response to minocycline.
The purpose of this study is to determine whether minocycline and aspirin are effective in the treatment of depression in individuals with bipolar disorder.