Effectiveness of Adjuvant Treatment of N-Acetylcysteine on Negative Symptoms and Neutrophil-Lymphocyte Ratio (NLR) in Schizophrenic Patients
Downloads
Highlights:
1. The essence of schizophrenia is the negative symptoms.
2. Adding meloxicam can improve the negative symptoms and changes in the NLR in schizophrenic patients.
Abstract
Introduction: Schizophrenia is a mental disorder that has a negative symptom domain. Negative symptoms are commonly referred to as the essence of schizophrenia. Treatment of negative symptoms is still considered less than optimal. The ratio of neutrophils and lymphocytes is one of the markers of inflammation. This study aimed to analyze the effectiveness of N-acetylcysteine as adjuvant therapy for improving negative symptoms and changes in the neutrophil-lymphocyte ratio (NLR) in schizophrenic patients.
Methods: This was a quasi-experimental study using a single-blind, pretest–post-test design. The subjects were 34 schizophrenic patients who were inpatients at Dr. Arif Zainuddin Regional Mental Hospital (RSJD), Surakarta, from May to July 2020. The subjects were assigned using a purposive sampling technique based on inclusion criteria and received adjuvant N-acetylcysteine therapy at 400 mg/day for 4 weeks. Data collection was obtained from medical records, interviews, field notes, positive scale, negative scale, and general psychopathology scale (PANSS) assessment sheets, and blood NLR examinations. Data analysis used SPSS 25.0.
Results: There was a significant difference between the treatment and control groups in reducing negative PANSS subscale measurement after adjuvant N-acetylcysteine treatment. However, there was no significant difference between the control and treatment groups after N-acetylcysteine administration for NLR.
Conclusion: The dose of adjuvant therapy N-acetylcysteine given to patients in this study had an effect on decreasing the negative subscale PANSS score.
Saha S, Chant D, McGrath J. Meta-Analyses of the Incidence and Prevalence of Schizophrenia: Conceptual and Methodological Issues. Int J Methods Psychiatr Res 2008; 17: 55–61.
Simeone JC, Ward AJ, Rotella P, et al. An Evaluation of Variation in Published Estimates of Schizophrenia Prevalence from 1990─2013: A Systematic Literature Review. BMC Psychiatry 2015; 15: 193.
Chang WC, Wong CSM, Chen EYH, et al. Lifetime Prevalence and Correlates of Schizophrenia-Spectrum, Affective, and Other Non-Affective Psychotic Disorders in the Chinese Adult Population. Schizophr Bull 2017; 43: 1280–1290.
Meyer U, Schwarz MJ, Müller N. Inflammatory Processes in Schizophrenia: A Promising Neuroimmunological Target for the Treatment of Negative/Cognitive Symptoms and Beyond. Pharmacol Ther 2011; 132: 96–110.
Carbon M, Correll CU. Thinking and Acting beyond the Positive: The Role of the Cognitive and Negative Symptoms in Schizophrenia. CNS Spectr 2014; 19 Suppl 1: 37-38,53.
Remington G, Foussias G, Fervaha G, et al. Treating Negative Symptoms in Schizophrenia: An Update. Curr Treat Options Psychiatry 2016; 3: 133–150.
Indriani S, Yasa A, Wasyanto T. Effects of N-Acetylcystein on Hscrp Level in Acute Myocardial Infarction Patients Receiving Fibrinolytic Therapy. Indones J Cardiol; 39. Epub ahead of print 11 September 2019.
Breier A, Liffick E, Hummer TA, 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; 199: 395–402.
Lolobua MFIP, Khairina K, Wardani IAK, et al. Negative Symptoms Management in Schizophrenia. J Psikiatri Surabaya 2021; 10: 6–12.
Syulthoni ZB, Gunadi IGN. Cognitive Enhancement Therapy in Schizophrenia. J Psikiatri Surabaya 2020; 9: 7–13.
Fitryasari R, Nursalam N, Yusuf A, et al. Development of a Family Resiliency Model to Care of Patients with Schizophrenia. Scand J Caring Sci 2021; 35: 642–649.
Jessica L, Fithriyah I, Ardani IGAI. The Importance of Family Support in Successful Treatment Adherence of Schizophrenic Patient. J Psikiatri Surabaya 2021; 10: 83–91.
Sari SP, Wijayanti DY. Spirituality Nursing among Patients with Schizophrenia. J Ners 2017; 9: 126–132.
Arisyna A, Sustini F, Muhdi N. Anxiety Level and Risk Factors in Medical Students. JUXTA J Ilm Mhs Kedokt Univ Airlangga 2020; 11: 79–82.
Mitra S, Natarajan R, Ziedonis D, et al. Antioxidant and Anti-Inflammatory Nutrient Status, Supplementation, and Mechanisms in Patients with Schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2017; 78: 1–11.
Zahnia S, Sumekar DW. Kajian Epidemiologis Skizofrenia. Majority 2016; 5: 160–166.
Sadock BJ, Sadock VA, Ruiz P. Kaplan & Sadock's Comprehensive Textbook of Psychiatry. Wolters Kluwer, https://books.google.co.id/books?id=gsDljwEACAAJ (2017).
Millan MJ, Fone K, Steckler T, et al. Negative Symptoms of Schizophrenia: Clinical Characteristics, Pathophysiological Substrates, Experimental Models and Prospects for Improved Treatment. European Neuropsychopharmacology : The Journal of the European College of Neuropsychopharmacology 2014; 24: 645–692.
Tong Z, Zhu J, Wang J-J, et al. The Neutrophil-Lymphocyte Ratio is Positively Correlated with Aggression in Schizophrenia. Biomed Res Int 2022; 2022: 4040974.
Yüksel RN, Ertek IE, Dikmen AU, et al. High Neutrophil-Lymphocyte Ratio in Schizophrenia Independent of Infectious and Metabolic Parameters. Nord J Psychiatry 2018; 72: 336–340.
Brinn A, Stone J. Neutrophil-Lymphocyte Ratio across Psychiatric Diagnoses: A Cross-Sectional Study Using Electronic Health Records. BMJ Open 2020; 10: e036859.
Stahl SM. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. New York, NY, US: Cambridge University Press, 2013.
Sayin U. Getting High on Dopamine: Neuroscientific Aspects of Pleasure. SexuS J 2019; 4: 883–906.
Laskaris LE, Di Biase MA, Everall I, et al. Microglial Activation and Progressive Brain Changes in Schizophrenia. Br J Pharmacol 2016; 173: 666–680.
Perkins DO, Jeffries CD, Do KQ. Potential Roles of Redox Dysregulation in the Development of Schizophrenia. Biol Psychiatry 2020; 88: 326–336.
Sepehrmanesh Z, Heidary M, Akasheh N, et al. Therapeutic Effect of Adjunctive N-Acetyl Cysteine (NAC) on Symptoms of Chronic Schizophrenia: A Double-Blind, Randomized Clinical Trial. Prog Neuropsychopharmacol Biol Psychiatry 2018; 82: 289–296.
Atmoko W, Purwanto B, Sugiarto S. Pengaruh Terapi N-Asetil Sistein terhadap Ekspresi Interleukin 17 dan Fibrosis Interstisial pada Mencit Nefritis Lupus. Biomedika; 9. Epub ahead of print 8 March 2018.
Karageorgiou V, Milas GP, Michopoulos I. Neutrophil-to-Lymphocyte Ratio in Schizophrenia: A Systematic Review and Meta-Analysis. Schizophr Res 2019; 206: 4–12.
Bavarsad Shahripour R, Harrigan MR, Alexandrov A V. N-Acetylcysteine (NAC) in Neurological Disorders: Mechanisms of Action and Therapeutic Opportunities. Brain Behav 2014; 4: 108–122.
BoÅ¡ković M, Vovk T, KoprivÅ¡ek J, et al. Vitamin E and Essential Polyunsaturated Fatty Acids Supplementation in Schizophrenia Patients Treated with Haloperidol. Nutr Neurosci 2016; 19: 156–161.
Cai HQ, Catts VS, Webster MJ, et al. Increased Macrophages and Changed Brain Endothelial Cell Gene Expression in the Frontal Cortex of People with Schizophrenia Displaying Inflammation. Mol Psychiatry 2020; 25: 761–775.
Jaehne A, Unbehaun T, Feige B, et al. Sleep Changes in Smokers before, during and 3 Months after Nicotine Withdrawal. Addict Biol 2015; 20: 747–755.
Fond G, D'Albis M-A, Jamain S, et al. The Promise of Biological Markers for Treatment Response in First-Episode Psychosis: A Systematic Review. Schizophr Bull 2015; 41: 559–573.
Drew L. Clozapine and Agranulocytosis: Re-Assessing the Risks. Australas Psychiatry 2013; 21: 335–337.
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.
Dominari A, Hathaway Iii D, Kapasi A, et al. Bottom-Up Analysis of Emergent Properties of N-Acetylcysteine as an Adjuvant Therapy for COVID-19. World J Virol 2021; 10: 34–52.
Tharoor H, Mara S, Gopal S. Role of Novel Dietary Supplement N-Acetyl Cysteine in Treating Negative Symptoms in Schizophrenia: A 6-Month Follow-up Study. Indian J Psychol Med 2018; 40: 139–142.
Camellia V, Khairunnisa K, Ichwan M, et al. The Augmentation Effect of N-Acetyl Cysteine Antioxidant on Superoxide Dismutase Levels in Schizophrenic Patients Treated with Risperidone. Open Access Maced J Med Sci 2021; 9: 321–324.
Yolland COB, Phillipou A, Castle DJ, et al. Improvement of Cognitive Function in Schizophrenia with N-Acetylcysteine: A Theoretical Review. Nutr Neurosci 2020; 23: 139–148.
Garcia-Serrano AM, Vieira JPP, Fleischhart V, et al. Taurine and N-Acetylcysteine Treatments Prevent Memory Impairment and Metabolite Profile Alterations in the Hippocampus of High-Fat Diet-Fed Female Mice. Nutr Neurosci 2022; 1–13.
Rogóż Z, KamiÅ„ska K, Lech MA, et al. N-Acetylcysteine and Aripiprazole Improve Social Behavior and Cognition and Modulate Brain BDNF Levels in a Rat Model of Schizophrenia. Int J Mol Sci; 23. Epub ahead of print February 2022.
Copyright (c) 2023 Ipak Ranto, Adriesti Herdaetha, Wijaya Kusuma
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
1. The journal allows the author to hold the copyright of the article without restrictions.
2. The journal allows the author(s) to retain publishing rights without restrictions
3. The formal legal aspect of journal publication accessibility refers to Creative Commons Atribution-Share Alike 4.0 (CC BY-SA).
