The purpose of this study is to evaluate minocycline as a potential treatment for bipolar depression when added to a mood-stabilizing medication. Minocycline is an antibiotic that is approved for the treatment of infections and acne. Participation in this research study is expected to last 8 weeks, and includes five outpatient visits.

Bipolar depression remains the great unmet need in the treatment of bipolar disorder. Only two treatments have been FDA-approved for the management of acute bipolar depression (the combination of olanzapine and fluoxetine and quetiapine). Early pilot data suggests the drug minocycline has potent antidepressant effects. Minocycline is approved by the Food and Drug Administration (FDA) (for acne and bacterial infections), is inexpensive and readily available in generic formulation, and is generally well-tolerated. This study will examine whether administering the drug minocycline to individuals with bipolar depression over 8 weeks will improve their depressive symptoms. This study will also offer an option to participate in proton magnetic resonance spectroscopy (1H-MRS) to measure N-Acetylaspartate (NAA) levels in the brain, which are thought to be decreased in bipolar disorder.

Inclusion Criteria:

• Meets DSM-IV criteria for Bipolar I Disorder or Bipolar II disorder, depressed phase
• A baseline score of at least 18 on the Montgomery-Asberg Depression Rating Scale (MADRS)
• Participants on mood stabilizer medication for at least two weeks prior to starting the study, and must remain on the treatment during the study
• Able to understand English

Exclusion Criteria:

• DSM-IV diagnosis of Bipolar NOS, Cyclothymia, or Schizoaffective Bipolar type
• Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy)
• Serious suicide or homicide risk
• Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease
• Clinical or laboratory evidence of hypothyroidism; if maintained on thyroid medication must be euthyroid for at least 1 month before visit 1
• Drug/alcohol dependence within past 30 days, or current substance use disorder that requires detoxification
• Current use of minocycline or history of anaphylactic reaction or intolerance to minocycline
• Primary clinical diagnosis of antisocial or borderline personality disorder
• Patients with metallic foreign bodies or claustrophobia will be excluded from the MRS component

Limitations are this is an open label study with no placebo and low number of subjects.