Investigating the Effect of N-Acetyl Cysteine on Positive, Negative, and Cognitive Symptoms of Patients with Schizophrenia: A Clinical Trial

Abstract

Background: Recent studies have identified oxidative stress as a potential neurobiological contributor to the development of schizophrenia. N-acetylcysteine (NAC) is recognized for its potent antioxidant and neuroprotective properties. Objectives: This study aimed to evaluate the efficacy of NAC in reducing oxidative stress as a treatment for schizophrenia. Methods: This randomized, double-blind, placebo-controlled, parallel-group study involved 35 patients with schizophrenia. Patients in the case group received 600 mg of NAC once daily in addition to their routine treatment, while the control group continued their routine treatment with a placebo instead of NAC. Assessments were conducted using the Scale for Assessment of Positive Symptoms (SAPS), the Scale for Assessment of Negative Symptoms (SANS), and the neuropsychiatry unit cognitive assessment tool (NUCOG) at baseline, and 1 and 2 months post-treatment. Results: N-acetylcysteine treatment resulted in a significant improvement in SAPS and NUCOG indices, as well as an increase in peripheral glutathione (GSH) levels (P < 0.05). Continued NAC use in the second month positively affected NUCOG indices, particularly the Visuo-constructional variable. No significant impact on SANS was observed. The limited side effects of NAC during the study period suggest it is a safe and practical treatment option. Conclusions: N-acetylcysteine add-on therapy significantly improved positive symptoms and cognitive functions in patients with schizophrenia but did not affect negative symptoms. © 2025, Soheilipour et al.