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Prog Neuropsychopharmacol Biol Psychiatry. 2018 Mar 2;82:289-296. doi: 10.1016/j.pnpbp.2017.11.001. Epub 2017 Nov 7.

Therapeutic effect of adjunctive N-acetyl cysteine (NAC) on symptoms of chronic schizophrenia: A double-blind, randomized clinical trial.

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Department of psychiatry, School of Medicine, Kashan University of Medical Science, Kashan, Iran.
Department of psychiatry, School of Medicine, Kashan University of Medical Science, Kashan, Iran. Electronic address:
School of Medicine, Qazvin University of Medical Science, Qazvin, Iran.
Department of Public Health, Kashan University Of Medical Sciences, kashan, Iran.
Department of Clinical Psychology, Qom Islamic Azad University, Qom, Iran. Electronic address:



Schizophrenia is one of the most disabling psychiatric syndromes with the prevalence of 1% in the general population. Despite availability of various antipsychotics, negative symptoms and cognitive impairment are difficult to treat. In addition antipsychotic monotherapy is not effective in most of these patients. Current evidence indicates the roles of glutamatergic system in this disorder. N-acetyl cysteine (NAC) also increases extracellular glutamate. This study was conducted to evaluate the clinical effects of oral NAC as an add-on to maintenance medication for the treatment of chronic schizophrenia.


This 12-week, double-blind, randomized, placebo-controlled, clinical trial was performed to determine the effectiveness of 1200mg N-acetyl cysteine as an adjunctive treatment with conventional antipsychotic medications in 84 patients with chronic schizophrenia. The subjects were evaluated with the Positive and Negative Syndrome Scale (PANSS), Mini-Mental State Examination (MMSE), and a standard neuropsychological screening test. Data were analyzed with SPSS-16 software.


NAC-treated patients showed significantly improvement in the positive (F=5.47, P=0.02) and negative (F=0.20, df=1) PANSS subscale. Also the general and total PANSS score of NAC group declined over times whilst it was increased for placebo group. Regarding cognitive functions, improvement was observed in some explored areas, such as attention, short-term and working memory, executive functioning and speed of processing. There was no significant difference between the 2 groups in the frequency of adverse effects.


The present study detected improvement in positive, negative, general and total psychopathology symptoms as well as cognitive performance with NAC treatment. It is also well-tolerated, safe and easy-to-use agent as an effective therapeutic strategy to improve outcome in schizophrenia treatment.


Cognitive impairment; Glutamatergic system; N-acetyl cysteine; Positive and negative symptoms scale (PANSS); Schizophrenia

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