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Does NAC help schizophrenia or schizoaffective disorder?

Maybe a little, and only as an add-on. In the trials, people with schizophrenia kept taking their antipsychotic and added NAC (N-acetylcysteine). Some trials lasting 6 months or longer found negative symptoms (loss of motivation and of emotional expression) eased slightly, but a 2024 review of 8 trials with 594 people found no clear difference on any symptom score. Grade B, mixed. Never stop or change an antipsychotic on your own.

Last reviewed

How we grade evidenceEditorial policy

What the studies found

  • Grade B. Add-on NAC helped in some longer trials. In 140 people with long-term schizophrenia who stayed on their antipsychotic, NAC taken by mouth, 1 g twice a day for 24 weeks, improved total, negative and general scores on the PANSS (a standard symptom scale) more than placebo; positive symptoms (hallucinations and delusions) did not change. A 52-week trial in 60 people early in the illness found gains in total and negative scores, but not in positive symptoms or thinking tests. (Berk 2008; Breier 2018)
  • Grade B. Other trials found no symptom benefit. In 63 people with early psychosis, NAC tablets (2,700 mg a day) for 6 months did not change negative or positive symptoms, though processing speed improved. In 84 people still unwell on clozapine, some with schizoaffective disorder, NAC capsules (2 g a day) for a year made no difference to negative symptoms, thinking or quality of life. (Conus 2018; Neill 2022)
  • Grade B. Pooled reviews disagree. A 2020 review found better negative and total scores only once treatment had run 24 weeks or more, plus better working memory. A 2024 review of 8 trials with 594 people found no difference in any symptom score. (Yolland 2020; Zhang 2024)
  • Grade C. We found no trial of NAC in schizoaffective disorder on its own. A 2025 analysis of supplement add-on trials in schizophrenia and schizoaffective disorder found NAC beat placebo on total symptoms in stable patients, but rated the quality of the evidence low to very low. (Fornaro 2025)

Who should be careful

  • NAC was only ever tested on top of antipsychotic medicine. Don't stop or change an antipsychotic, mood stabilizer or antidepressant on your own; ask your psychiatrist first.
  • In these trials, side effects and dropouts were about the same with NAC as with placebo (Neill 2022; Zhang 2024).
  • No interaction studies of NAC with antipsychotics, clozapine or mood stabilizers were found. Tell your psychiatrist and pharmacist before you add it.
  • Get help the same day if voices or fears get louder, you stop sleeping for days, you can't look after yourself, or you have thoughts of harming yourself or someone else. In the US, call or text 988, or go to an emergency room.
  • If you are pregnant, breastfeeding or under 18, ask a clinician first.

Try first

  • Stay with psychiatric care. The UK's national guideline (NICE) advises antipsychotic medicine together with individual cognitive behavioral therapy (CBT) and family intervention, and a combined healthy eating and physical activity program (NICE CG178).
  • Regular exercise: in a 2015 review, programs with about 90 minutes of moderate-to-vigorous exercise a week reduced psychiatric symptoms in schizophrenia (Firth 2015).

Sources

  1. Berk M, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008. PubMed 18436195 · doi:10.1016/j.biopsych.2008.03.004
  2. Breier A, et al. Effects of 12-month, double-blind N-acetyl cysteine on symptoms, cognition and brain morphology in early phase schizophrenia spectrum disorders. Schizophr Res. 2018. PubMed 29588126 · doi:10.1016/j.schres.2018.03.012
  3. Conus P, et al. N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis. Schizophr Bull. 2018. PubMed 29462456 · doi:10.1093/schbul/sbx093
  4. Neill E, et al. N-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptoms. Schizophr Bull. 2022. PubMed 35857752 · doi:10.1093/schbul/sbac065
  5. Yolland CO, et al. Meta-analysis of randomised controlled trials with N-acetylcysteine in the treatment of schizophrenia. Aust N Z J Psychiatry. 2020. PubMed 31826654 · doi:10.1177/0004867419893439
  6. Zhang Q, et al. Efficacy and acceptability of adjunctive n-acetylcysteine for psychotic disorders: Systematic review and meta-analysis. Hum Psychopharmacol. 2024. PubMed 37712506 · doi:10.1002/hup.2880
  7. Fornaro M, et al. Nutraceuticals and phytoceuticals in the treatment of schizophrenia: a systematic review and network meta-analysis "Nutra NMA SCZ". Mol Psychiatry. 2025. PubMed 39026098 · doi:10.1038/s41380-024-02645-y
  8. Firth J, et al. A systematic review and meta-analysis of exercise interventions in schizophrenia patients. Psychol Med. 2015. PubMed 25650668 · doi:10.1017/S0033291714003110