A Pilot Study Investigating the Efficacy of Minocycline and N-Acetyl Cysteine for Bipolar Depression

Inclusion Criteria: 1. Able to give written informed consent and follow study procedures 2. Age \> or = 18 years and \< or = 65 years 3. Meets Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) criteria for Bipolar Disorder Type I, which is the primary focus of treatment 4. Currently depressed, as defined by a Montgomery-Asberg Depression Rating Scale (MADRS) score of \> or = 18 at screen and baseline (randomization) 5. Participants will remain on baseline mood stabilizer pharmacotherapy with lithium during the study. They will need to have been on lithium with stable therapeutic blood levels for at least two weeks prior to randomization and agree not to change medications during the study. 6. Women of child bearing potential must agree to use adequate contraception (e.g. oral contraceptives, intrauterine device, double barrier methods), if sexually active. Depo Provera is acceptable if it is started 3 months prior to enrollment. If hormonal contraceptives are used, participants must also agree to use a backup method of birth control. They will also need to understand the risks of lithium and other study treatments to the fetus and infant. Exclusion Criteria: 1. Unwilling or unable to comply with study requirements 2. Patients who are a serious suicide or homicide risk, or currently in crisis such that inpatient hospitalization or other crisis management should take priority 3. DSM-V diagnosis of Bipolar Disorder not otherwise specified, cyclothymia, schizoaffective bipolar type 4. Primary anxiety disorders (e.g. Panic disorder, generalized anxiety disorder, post-traumatic stress disorder) or patients where the anxiety disorder is the primary focus of treatment 5. Any history of obsessive compulsive disorder (OCD) or OCD-spectrum disorders 6. Clinical or laboratory evidence of hypothyroidism; if maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1 7. Subjects having failed two or more trials of somatic therapy (i.e. medications for bipolar depression or Food and Drug Administration-approved devices) during the current bipolar depressive episode 8. Drug/alcohol abuse or dependence active within the past 3 months, or current substance use disorder that requires detoxification 9. Pregnancy (as determined by urine pregnancy test) 10. Suspected or known clinically unstable systemic medical disorder including epilepsy, untreated endocrine disease, unstable angina, recent ulcers or significant esophagitis 11. Conditions which may be negatively affected by minocycline treatment, such as inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease) 12. History of significant treatment non-adherence or situations where the subject is unlikely to adhere to treatment, in the opinion of the investigator 13. Current use of minocycline or history of anaphylactic reaction or intolerance to minocycline or any component of the preparation 14. Current use of greater than 500mg of NAC/day, 200ug of selenium/day or 500 IU of Vitamin E/day 15. History of anaphylactic reaction or intolerance to NAC or any component of the preparation 16. A primary clinical diagnosis of a personality disorder, or comorbid diagnosis of antisocial or borderline personality disorder 17. A history of C. difficile colitis 18. A history of tetracycline allergy 19. Liver enzymes above the upper limit of normal