N-acetylcysteine (NAC)

Class

Antioxidant and glutathione precursor

Mechanism

Modulates glutamatergic neurotransmission and reduces oxidative stress by replenishing intracellular glutathione; may regulate neuroinflammation and mitochondrial function

FDA-Approved Use

Acetaminophen toxicity

Off-Label Use

Augmentation in major depressive disorder (MDD), bipolar disorder (BD), obsessive-compulsive disorder (OCD), substance use disorders (SUD)

Formulation

Oral capsules, tablets, and powder

Titration

600 mg twice daily, titrated up to 1,200–3,000 mg/day in divided doses (BID or TID) as tolerated

Dose Range

1,200–3,000 mg/day

Kinetics

Well absorbed orally; undergoes first-pass metabolism; plasma half-life ~5.6 hours

Common AEs

Gastrointestinal upset, flatulence, rarely rash or headache

Serious/Rare AEs

Rare hypersensitivity reactions; generally well tolerated

Monitoring

No routine labs required; monitor for tolerance and adverse effects

Black Box Warning

None

Considerations

Limited evidence suggests NAC may reduce compulsivity, irritability, and repetitive behaviors in traumatic brain injury (TBI), autism spectrum disorder (ASD), and dementia-related agitation. It is also considered for craving reduction in substance use disorders. Generally well tolerated across neurological and psychiatric populations.