N-Acetylcysteine as an Adjunct to Risperidone for Treatment of Negative Symptoms in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study
Abstract
Objectives Despite the burden of negative symptoms on quality of life in schizophrenic patients, no completely effective treatment has been developed to address such symptoms yet. Abnormalities in oxidative stress pathways have been recently demonstrated to be involved in the pathophysiology of schizophrenia, and a growing interest in antioxidant agents is emerging for targeting negative symptoms of schizophrenia. N-Acetylcysteine (NAC) is a potent antioxidant with neuroprotective properties. This study aimed to evaluate the possible effects of NAC as an adjunct to risperidone in treating negative symptoms of schizophrenia. Materials and methods In this randomized, double-blind, placebo-controlled, parallel-group study, 42 patients with chronic schizophrenia and a score of 20 or greater on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. The participants were equally randomized to receive NAC (up to 2 g/d) or placebo, in addition to risperidone (up to 6 mg/d) for 8 weeks. The participants were rated using PANSS every 2 weeks, and the decrease of PANSS negative subscale score was considered as our primary outcome. Results By the study end point, NAC-treated patients showed significantly greater improvement in the PANSS total (P = 0.006) and negative subscale (P Conclusions NAC add-on therapy showed to be a safe and effective augmentative strategy for alleviating negative symptoms of schizophrenia.
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Results from a small-scale trial suggest that N-acetylcysteine (in addition to antipsychotics) may improve negative symptoms and social functioning in schizophrenia patients.
“Consistent with this, results from a small-scale trial suggest that N -acetylcysteine (in addition to antipsychotics) may improve negative symptoms and social functioning in schizophrenia patients 85 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [85]
Two additional studies demonstrated that chronic patients improved with add-on NAC, particularly in their negative symptoms.
“Two additional studies also demonstrated that chronic patients improved with add-on NAC, particularly in their negative symptoms (Bulut et al., 2009; Farokhnia et al., 2013).”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Farokhnia et al., 2013
The potential for juvenile NAC treatment to prevent the emergence of electrophysiological and behavioural deficits in a rodent developmental model of schizophrenia suggests that prophylactic treatment for high-risk groups may be effective.
“The potential for juvenile NAC treatment to prevent the emergence of electrophysiological and behavioural deficits in a rodent developmental model of schizophrenia 56 suggests that prophylactic treatment for high-risk groups may be effective, particularly with a drug or dietary supplement with a good safety profile like NAC or polyunsaturated fatty acids such as omega 3s 105 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [105]
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- Authors
- Farokhnia, M., Azarkolah, A., Adinehfar, F., Khodaie-Ardakani, M.-R., Hosseini, S.-M.-R., Yekehtaz, H., Tabrizi, M., Rezaei, F., Salehi, B., Sadeghi, S.-M.-H., Moghadam, M., Gharibi, F., Mirshafiee, O., & Akhondzadeh, S.
- Affiliations
- Arak University of Medical Sciences (IR)
- Razi Hospital (IR)
- Tehran University of Medical Sciences (IR)
- Kurdistan University of Medical Sciences (IR)
- Corresponding author
- Farokhnia, Mehdi
- Azarkolah, Anita
- Hosseini, Seyed-Mohammad-Reza
- Yekehtaz, Habibeh
- Mirshafiee, Omid
- Akhondzadeh, Shahin
- ORCID
- Venue
- Clinical Neuropharmacology
- Published
- 2013-11
- Volume
- 36
- Issue
- 6
- Pages
- 185-192
- ISSN
- 0362-5664 (ISSN-L)
- OpenAlex
- W2035477056
- Cited by
- 155
- References
- 9
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 11 · 2023: 11 · 2022: 11 · 2021: 15 · 2020: 11 · 2019: 19 · 2018: 14 · 2017: 9 · 2016: 12 · 2015: 10 · 2014: 11
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- N-acetylcysteine, risperidone, negative symptoms of schizophrenia, chronic schizophrenia, adjunctive therapy, oxidative stress, antioxidant therapy, neuroprotection, antipsychotic augmentation
- MeSH terms
- Acetylcysteine, Adult, Chronic Disease, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Free Radical Scavengers, Treatment Outcome, Risperidone
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