Evaluating the Hypothesized Mechanism of Action of N-acetylcysteine for Bipolar Disorder

Inclusion criteria

• Ages 18-60 years
• Meet DSM-5 criteria for bipolar I or II disorder
• Able to provide informed consent and read, understand, and accurately complete assessment instruments
• Willing to commit to medication treatment and follow-up assessments
• Meets DSM-5 criteria for any mood episode (i.e., Major Depressive, Hypomanic, Manic), Current or In Partial Remission
• Prescribed daily use of at least one FDA-approved mood stabilizing medication (i.e., lithium, divalproex sodium, lamotrigine, 2nd generation antipsychotic)
• Willing to abstain from antioxidant supplements (e.g., coenzyme Q-10, vitamin E) for the duration of the study.

Exclusion criteria

• A primary psychiatric diagnosis other than BD (e.g., Schizophrenia)
• Meet DSM-5 criteria for substance use disorder (other than Tobacco Use Disorder) within the past 6 months.
• Any uncontrolled neurological condition (e.g., epilepsy) that could confound the results of the study
• Any history of brain injury with loss of consciousness greater than 5 minutes
• Any history of mental retardation, dementia, or recent electroconvulsive therapy (in the past 3 months)
• Any uncontrolled medical condition that may adversely affect the conduct of the study or jeopardize the safety of the participant
• Hepatocellular disease as indicated by plasma levels of liver transaminases (aspartate transaminase, alanine transaminase) greater than 3 times the normal range
• Renal insufficiency as indicated by plasma levels of creatinine greater than 2 times the normal range
• Concomitant use of nitroglycerine, carbamazepine, or any other medication deemed to be hazardous if taken with N-Acetylcysteine (NAC).
• Medication dose changes of ≥ 20% ≤ 2 weeks prior to testing
• Women of childbearing potential who are pregnant, lactating, or refuse adequate forms of contraception
• Current suicidal or homicidal risk
• Baseline scores greater than 35 on the Montgomery-Asberg Depression Rating Scale or greater than 25 on the Young Mania Rating Scale
• Has taken NAC in the last month or experienced adverse effects/allergic reaction from it at any time
• Significant claustrophobia and/or past negative experiences with MRI
• Presence of non-MRI safe materials in the body (e.g., ferrous metal implants, pacemaker)