The double-blind randomized placebo-controlled trial of N-acetylcysteine use in schizophrenia: preliminary results

Pyatoykina A.S.; Zhilyaeva T.V.; Semennov I.V.; Mishanov G.A.; Blagonravova A.S.; Mazo G.E.

doi:https://doi.org/10.17116/jnevro202012009166

Pyatoykina A.S.

Clinical Psychiatric Hospital No. 1

Zhilyaeva T.V.

Privolzhsky Research Medical University

Semennov I.V.

Privolzhsky Research Medical University

Mishanov G.A.

Privolzhsky Research Medical University

Blagonravova A.S.

Privolzhsky Research Medical University

Mazo G.E.

Bekhterev National Medical Research Center for Psychiatry and Neurology

ORCID: 0000-0001-7910-9129

The double-blind randomized placebo-controlled trial of N-acetylcysteine use in schizophrenia: preliminary results

Authors:

Pyatoykina A.S., Zhilyaeva T.V., Semennov I.V., Mishanov G.A., Blagonravova A.S., Mazo G.E.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2020;120(9): 66‑71

DOI: 10.17116/jnevro202012009166

Read: 8243 times

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Pyatoykina AS, Zhilyaeva TV, Semennov IV, Mishanov GA, Blagonravova AS, Mazo GE. The double-blind randomized placebo-controlled trial of N-acetylcysteine use in schizophrenia: preliminary results. S.S. Korsakov Journal of Neurology and Psychiatry. 2020;120(9):66‑71. (In Russ.)
https://doi.org/10.17116/jnevro202012009166

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

Использование инфографики авторами научных работ

Close metadata

BACKGROUND

Currently, oxidative stress as part of the pathogenesis of schizophrenia attracts much attention. In this regard, it becomes relevant to assess the level of redox imbalance in patients with schizophrenia, its impact on existing symptoms and the possibility of its treatment. The antioxidant N-acetylcysteine is one of the potential drugs that affects oxidative stress.

OBJECTIVE

To study the possibilities of the use of N-acetylcysteine in patients with schizophrenia.

MATERIAL AND METHODS

The study included 20 patients diagnosed with paranoid schizophrenia with the disease duration of less than 3 years, randomly assigned to the main group (taking N-acetylcysteine at a dose of 2000 mg per day for 60 days) and a comparison group (placebo) in a double-blinded manner. At the beginning and end of the study, cognitive functions were evaluated using the specialized instrument BACS, the severity of psychopathological symptoms was evaluated using PANSS, and blood was collected to determine the level of glutathione (GSH), which is a metabolite of N-acetylcysteine.

RESULTS

There was a significant decrease in positive PANSS score (p=0.013), negative PANSS score (p=0.002) and the general pathology PANSS score (p=0.004) in the main group. Compared with the comparison group, the dynamics of the negative PANSS score (p=0.005) and the general psychopathology PANSS score (p=0.004) was significantly different. When assessing the dynamics of cognitive functions in the main group, a significant improvement in indicators was established in the task for a sequence of numbers that characterizes working memory (p=0.037). The level of GSH significantly increased in the main group (p=0.01), however, there were no statistically significant differences between groups at the final visit.

CONCLUSION

N-acetylcysteine has a positive effect on the negative, general psychopathology PANSS scores, some cognitive functions, in particular, working memory, that allows considering this drug as a promising method of augmentation of schizophrenia therapy and requires further attentive study.

Keywords:

schizophrenia

oxidative stress

glutathione

N-acetylcysteine

Authors:

Pyatoykina A.S.

Clinical Psychiatric Hospital No. 1

Zhilyaeva T.V.

Privolzhsky Research Medical University

Semennov I.V.

Privolzhsky Research Medical University

Mishanov G.A.

Privolzhsky Research Medical University

Blagonravova A.S.

Privolzhsky Research Medical University

Mazo G.E.

Bekhterev National Medical Research Center for Psychiatry and Neurology

ORCID: 0000-0001-7910-9129

Received:

16.02.2020

Accepted:

20.03.2020

Close metadata

References:

Newton DF, Naiberg MR, Goldstein BI. Oxidative stress and cognition amongst adults without dementia or stroke: implications for mechanistic and therapeutic research in psychiatric disorders. Psychiatry Res. 2015 Jun 30;227(2-3):127-134. https://doi.org/10.1016/j.psychres.2015.03.038
Lutskij MA, Kuksova TV, Smelyanets MA, Lushnikova YP. Lipid and protein free-radical oxidation as a universal vital process of the organism. Uspekhi sovremennogo estestvoznaniya. 2014;12(1):24-28. (In Russ.).
Danilov DS, Volkov VP. The cardiotoxicity of neuroleptics. Tver: Triada; 2018;622. S.S. Korsakov Journal of Neurology and Psychiatry = Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2019;119(5):173-174. (In Russ.). https://doi.org/10.17116/jnevro2019119051173
Maas DA, Vallès A, Martens GJM. Oxidative stress, prefrontal cortex hypomyelination and cognitive symptoms in schizophrenia. Transl Psychiatry. 2017;7(7):e1171. https://doi.org/10.1038/tp.2017.138
Burminskiy DS. Residual psychotic symptoms in remission of paroxysmal-progressive schizophrenia: clinical typology and therapeutic approaches. Dis. ... kand. med. nauk.M.: NCPZ RAN. 2018;24-25. (In Russ.).
Boyko AS. Oxidative stress and glutamatergic excitotoxicity in the development of drug-induced tardive dyskinesia. Fundamental’nye issledovaniya. 2014;10(6):1220-1226. (In Russ.).
Micó JA, Rojas-Corrales MO, Gibert-Rahola J, Parellada M, Moreno D, Fraguas D, Graell M, Gil J, Irazusta J, Castro-Fornieles J, Soutullo C, Arango C, Otero S, Navarro A, Baeza I, Martínez-Cengotitabengoa M, González-Pinto A. Reduced antioxidant defense in early onset ﬁrst-episode psychosis: a casecontrol study. BMC Psychiatry. 2011;11:26. https://doi.org/10.1186/1471-244X-11-26
Raffa M, Atig F, Mhalla A, Kerkeni A, Mechri A. Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive ﬁrst-episode schizophrenic patients. BMC Psychiatry. 2011;11:124. https://doi.org/10.1016/j.pnpbp.2009.06.018
Das TK, Javadzadeh A, Dey A, Sabesan P, Théberge J, Radua J, Palaniyappan L. Antioxidant defense in schizophrenia and bipolar disorder: A meta-analysis of MRS studies of anterior cingulate glutathione. Prog Neuropsychopharmacol Biol Psychiatry. 2019;91:94-102. https://doi.org/10.1016/j.pnpbp.2018.08.006
Nucifora LG, Tanaka T, Hayes LN, Kim M, Lee BJ, Matsuda T, Nucifora FC Jr, Sedlak T, Mojtabai R, Eaton W, Sawa A. Reduction of plasma glutathione in psychosis associated with schizophrenia and bipolar disorder in translational psychiatry. Transl Psychiatry. 2017;7(8):e1215. https://doi.org/10.1038/tp.2017.178
Ooi SL, Green R, Pak SC. N-Acetylcysteine for the Treatment of Psychiatric Disorders: A Review of Current Evidence. Biomed Res Int. 2018;2018:2469486. https://doi.org/10.1155/2018/2469486
Berk M, Copolov D, Dean O, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia—a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008;64:361-368.
Farokhnia M, Azarkolah A, Adinehfar F, et al. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2013;36:185-192. https://doi.org/10.1097/WNF.0000000000000001
Sepehrmanesh Z, Heidary M, Akasheh N, Akbari H, Heidary M. Therapeutic effect of adjunctive N-acetylcysteine (NAC) on symptoms of chronic schizophrenia: A double-blind, randomized clinical trial. Prog Neuropsychopharmacol Biol Psychiatry. 2018;82:289-296. https://doi.org/10.1016/j.pnpbp.2017.11.001
Yolland CO, Hanratty D, Neill E, Rossell SL, Berk M, Dean OM, Castle DJ, Tan EJ, Phillipou A, Harris AW, Barreiros AR, Hansen A, Siskind D. Cognitive effects of adjunctive N-acetylcysteine in psychosis. Psychol Med. 2017;47(5):866-876. https://doi.org/10.1017/S0033291716002932
Breier A, Liffick E, Hummer TA, Vohs JL, Yang Z, Mehdiyoun NF, Visco AC, Metzler E, Zhang Y, Francis MM. Effects of 12-month, double-blind N-acetylcysteine on symptoms, cognition and brain morphology in early phase schizophrenia spectrum disorders. Schizophr Res. 2018 Sep;199:395-402. https://doi.org/10.1016/j.schres.2018.03.012
Rapado-Castro M, Berk M, Venugopal K, Bush AI, Dodd S, Dean OM. Towards stage speciﬁc treatments: effects of duration of illness on therapeutic response to adjunctive treatment with N-acetylcysteine in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2015;57:69-75. https://doi.org/10.1016/j.pnpbp.2014.10.002
Conus P, Seidman LJ, Fournier M, Xin L, Cleusix M, Baumann PS, Ferrari C, Cousins A, Alameda L, Gholam-Rezaee M, Golay P, Jenni R, Woo TW, Keshavan MS, Eap CB, Wojcik J, Cuenod M, Buclin T, Gruetter R, Do KQ. N-acetylcysteine in a double-blind randomized placebo-controlled trial: toward biomarker-guided treatment in early psychosis. Schizophr Bull. 2018 Feb 15;44(2):317-327. https://doi.org/10.1016/j.eurpsy.2017.01.1560
Klauser P, Xin L, Fournier M, Griffa A, Cleusix M, Jenni R, Cuenod M, Gruetter R, Hagmann P, Conus P, Baumann PS, Do KQ. N-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: a double-blind randomized placebo-controlled trial. Transl Psychiatry. 2018;8(1):220. https://doi.org/10.1038/s41398-018-0266-8
Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261-276.
Keefe RS, Harvey PD, Goldberg TE, Gold JM, Walker TM, Kennel C, Hawkins K. Norms and standardization of the Brief Assessment of Cognition in Schizophrenia (BACS). Schizophr Res. 2008;102(1-3):108-115. https://doi.org/10.1016/j.schres.2008.03.024
Lingjaerde O, Ahlfors UG, Bech P, Dencker SJ, Elgen K. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatrica Scandinavica Supplementum. 1987;334:1-100. https://doi.org/10.1111/j.1600-0447.1987.tb10566.x
Addington D, Addington J, Schissel B. A depression rating scale for schizophrenics. Schizophr Res. 1990;3(4):247-251.
Morosini PL, Magliano L, Brambilla L, Ugolini S, Pioli R. Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta Psychiatr Scand. 2000;101(4):323-329.