N-Acetylcysteine for Bipolar and Alcohol Use Disorders

Inclusion Criteria:

1. Age 18 to 60 years.
2. Meet DSM-5 criteria for bipolar I or bipolar II disorder.
3. Prescribed daily use of at least one FDA-approved mood-stabilizing medication (lithium, divalproex sodium, lamotrigine, or a second-generation antipsychotic).
4. Meet DSM-5 criteria for current, within the past 90 days, moderate to severe alcohol use disorder.
5. Active alcohol use in the past 14 days, with heavy drinking days on at least 50% of drinking days in the past 30 days.
6. Able to provide informed consent and read, understand, and accurately complete assessment instruments.
7. Willing to commit to medication treatment and follow-up assessments.
8. Willing to abstain from antioxidant supplements for the duration of the study.

Exclusion Criteria:

1. Primary psychiatric diagnosis other than bipolar disorder.
2. Uncontrolled neurological condition that could confound study results.
3. History of brain injury with loss of consciousness greater than 5 minutes.
4. History of intellectual disability or dementia.
5. Uncontrolled medical condition that may adversely affect study conduct or participant safety.
6. Hepatocellular disease as defined in the protocol.
7. Renal insufficiency as defined in the protocol.
8. Concomitant use of nitroglycerin, carbamazepine, or another medication deemed hazardous with NAC.
9. Concomitant use of specified alcohol-use-disorder medications or medications that could interfere with glutamate transmission.
10. Electroconvulsive therapy in the past 3 months.
11. Medication dose change of 20% or greater within 2 weeks before testing.
12. Pregnancy, lactation, or refusal to use adequate contraception when applicable.
13. Current suicidal or homicidal risk.
14. Baseline MADRS score greater than 35 or YMRS score greater than 25.
15. Clinically significant alcohol withdrawal symptoms or autonomic instability.
16. NAC use in the last month or prior adverse effects from NAC.
17. Has an allergy to riboflavin
18. Significant claustrophobia or prior negative experience with MRI.
19. Non-MRI-safe material in the body.