The Effectiveness of Chlorpromazine to Decrease the Level of Tumor Necrosis Factor-Alpha Serum in Schizophrenic Patients with Coronavirus Disease 2019

Authors

  • Andi Jayalangkara Tanra Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
  • Ahmad Andi Sameggu Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
  • Rinvil Renaldi Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
  • Burhanuddin Bahar Department of Public Health, Faculty of Public Health, Hasanuddin University, Makassar, South Sulawesi, Indonesia
  • Saidah Syamsuddin Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
  • Muhammad Ilyas Department of Pulmonology, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia
  • Sonny T. Lisal Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.7702

Keywords:

Schizophrenia, Chlorpromazine, Tumor necrosis factor-alpha, Severe acute respiratory syndrome coronavirus 2, Coronavirus disease 2019

Abstract

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2. The COVID-19 pandemic has also had an impact on mental health, including those with schizophrenia (SCH). There were 131 inpatient schizophrenic patients who were confirmed positive for COVID-19 at Dadi Makassar Hospital, South Sulawesi, Indonesia, but all of these patients did not experience any clinical symptoms of COVID-19. Chlorpromazine as an antipsychotic also has antiviral and anti-inflammatory effects in schizophrenic patients with COVID-19, and the schizophrenic neuroinflammatory is very likely to occur in patients with COVID-19 infection.

AIM: The researchers tried to examine the effectiveness of chlorpromazine on serum TNF-values in schizophrenic patients with COVID-19.

METHODS: This research is a nested case–control study. The study was conducted on schizophrenic patients with mild and asymptomatic cases of COVID-19 at Dadi Mental Hospital with a sample of 40 patients compared to 42 schizophrenic patients who were not COVID-19. Study subjects received chlorpromazine 100 mg/day for 4 weeks. Serum tumor necrosis factor-alpha (TNF-α) concentrations were measured by enzyme-linked immunosorbent assays when COVID-19 was first confirmed and after 4 weeks. Positive and negative syndrome scale (PANSS) and clinical global impression SCH (CGI-SCH) examinations were also performed to measure the clinical symptoms of SCH.

RESULTS: The comparison of baseline TNF-serum levels that increased in the schizophrenic group with COVID-19 was 9.33 pg/ml higher, compared to the schizophrenic group without COVID-19. The decrease in TNF-levels in the schizophrenic group with COVID-19 of 7.96 pg/ml (p < 0.001) indicated an improvement in TNF-serum levels at week 4. Meanwhile, there was no significant decrease in serum TNF- levels in the non-COVID-19 schizophrenic group (p > 0.05).

CONCLUSION: The serum TNF-value of schizophrenic patients with COVID-19 is higher than schizophrenic patients without COVID-19. Coadministration of chlorpromazine, antipsychotics, and COVID-19 therapy reduces serum TNF- values in schizophrenic patients with COVID-19. The administration of chlorpromazine and antipsychotic in therapeutic doses reduced the total PANSS and CGI-SCH values.

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References

WHO. Clinical Management of Severe Acute Respiratory Infection when Novel Coronavirus (nCoV) Infection is Suspected. Geneva: WHO; 2020. Available from: https://www.who.int/internal-publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus- (ncov)-infection-is-suspected [Last accessed on 2020 Apr 21].

Coccolini F, Sartelli M, Kluger Y, Pikoulis E, Karamagioli E, Moore E. COVID-19 the showdown for mass casualty preparedness and management: The cassandra syndrome. World J Emerg Surg. 2020;15(1):26. https://doi.org/10.1186/s13017-020-00304-5 PMid:32272957 DOI: https://doi.org/10.1186/s13017-020-00304-5

Katlyn N, Chenxiang L, Mark O. Association of psychiatric disorders with mortality among patients with COVID-19. JAMA Psychiatry. 2021;78(4):1-7. DOI: https://doi.org/10.1001/jamapsychiatry.2020.4442

Hoertel N, Sachez-Rico M, Vernet R, Jannot AS, Neuraz A, Blanco C, et al. Observational study of chlorpromazine in hospitalized patients with COVID19. Clin Drug Investig. 2021;41(3):221-33. https://doi.org/10.1007/s40261-021-01001-0 PMid:33559821 DOI: https://doi.org/10.1007/s40261-021-01001-0

Arana GW. Antipsychotic Drugs in Handbook of Psychiatric Drug Therapy. Philadelphia, PA: Lippincot Williams & Wilkins; 2000.

Plaze M, Attali D, Petit A, Blatzer M, Simon-Loriere E, Vinckier F. Repurposing chlorpromazine to treat COVID-19: The reCoVery study. Encephale. 2020;46(3):169-72. https://doi.org/10.1016/j.encep.2020.05.006 PMid:32425222 DOI: https://doi.org/10.1016/j.encep.2020.05.006

Dyall J, Coleman C, Hart B, Venkataraman T, Holbrook M, Kindrachuk J. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014;58(8):4885-93. https://doi.org/10.1128/AAC.03036-14 PMid:24841273 DOI: https://doi.org/10.1128/AAC.03036-14

DeWilde A, Jochmans D, Posthuma C, Zevenhoven-Dobbe J, van Nieuwkoop S, Bestebroer T. No TitleScreening of an FDAapproved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome Coronavirus replication in cell culture. Am Soc Microbiol. 2014;8:4875-84. https://doi.org/10.1128/AAC.03011-14 PMid:24841269 DOI: https://doi.org/10.1128/AAC.03011-14

Daniel J, Chau N, Abdel-Hamid M, Hu L, VonKleist L, Whiting A. Phenothiazine-derived antipsychotic drugs inhibit dynamin and clathrin-mediated endocytosis. Traffic. 2015;16:635-54. https://doi.org/10.1111/tra.12272 PMid:25693808 DOI: https://doi.org/10.1111/tra.12272

Miller B, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Metaanalysis of cytokine alterations in schizophrenia: Clinical status and antipsychotic effects. Biol Psychiatry. 2011;70(7):663-71. https://doi.org/10.1016/j.biopsych.2011.04.0 PMid:21641581 DOI: https://doi.org/10.1016/j.biopsych.2011.04.013

Bertini R, Garattini S, Delgado R, Ghezzi P. Pharmacological activities of chlorpromazine involved in the inhibition of tumour necrosis factor production in vivo in mice. Immunology. 1993;79:217-9. PMid:8102118

Himmerich H, Schonherr J, Fulda S, Sheldrick AJ, Bauer K, Sack U. Impact of antipsychotics on cytokine production in vitro. J Psychiatr Res. 2011;45(10):1358-65. https://doi.org/10.1016/j.jpsychires.2011.04.009 PMid:21592521 DOI: https://doi.org/10.1016/j.jpsychires.2011.04.009

Lee EE, Hong S, Martin AS, Eyler LT, Jeste DV. Inflammation in schizophrenia: Cytokine levels and their relationships to demographic and clinical variables. Am J Geriatr Psychiatry. 2017;25(1):50-61. https://doi.org/10.1016/j.jagp.2016.09.009 PMid:27840055 DOI: https://doi.org/10.1016/j.jagp.2016.09.009

Suchanek-Raif R, Raif P, Kowalczyk M, Paul-Samojedny M, Kucia K, Merk W. Promoter polymorphisms of TNF-a gene as a risk factor for schizophrenia. Arch Med Res. 2018;49:248-54. https://doi.org/10.1016/j.arcmed.2018.09.007. PMid:30268704 DOI: https://doi.org/10.1016/j.arcmed.2018.09.007

Narla S, Lee Y, Benson C, Sarder P, Brennand K, Stachowiak E. Common developmental genome deprogramming in schizophrenia-role of integrative nuclear FGFR1 signaling (INFS). Schizophr Res. 2017;185:17-32. https://doi.org/10.1016/j.schres.2016.12.012 PMid:28094170 DOI: https://doi.org/10.1016/j.schres.2016.12.012

Gennaro F, Pizzol D, Marotta C, Antunes M, Racalbuto V, Veronese N, et al. Coronavirus diseases (COVID-19) current status and future perspectives: A narrative review. Int J Environ Res Public Health. 2020;17(8):2690. https://doi.org/10.3390/ijerph17082690 PMid:32295188 DOI: https://doi.org/10.3390/ijerph17082690

Malavika L, Goyal T, Ghosh R, Suri S, Mitra P. Inflammation, immunity and immunogenetics in COVID-19: A narrative review. Indian J Clin Biochem. 2020;35(3):260-73. https://doi.org/10.1007/s12291-020-00897-3 PMid:32641873 DOI: https://doi.org/10.1007/s12291-020-00897-3

Stip E, Rizvi TA, Farah Mustafaa SJ, Aburuz S, Ahmed NN, Aziz KA, et al. The large action of chlorpromazine: Translational and transdisciplinary considerations in the face of COVID-19. Front Pharmacol. 2020;11:577678. https://doi.org/10.3389/fphar.2020.577678 PMid:33390948 DOI: https://doi.org/10.3389/fphar.2020.577678

Leucht S, Kane J, Kissling W, Hamann J, Etschel E, Engel R. What does the PANSS mean? Schizophr Res. 2005;79(2-3):231-8. https://doi.org/10.1016/j.schres.2005.04.008 PMid:15982856 DOI: https://doi.org/10.1016/j.schres.2005.04.008

Haro J, Kamath S, Ochoa S. The clinical global impressionschizophrenia scale: A simple instrument to measure the diversity of symptoms present in schizophrenia. Acta Psychiatr Scand. 2003;107(416):16-23. https://doi.org/10.1034/j.1600-0447.107.s416.5.x PMid:12755850 DOI: https://doi.org/10.1034/j.1600-0447.107.s416.5.x

Sadock B, Sadock V, Ruiz P. Schizophrenia spectrum and other psychotic disorder. In: Kaplan and Sadock’s Synopsis of Psychiatry Behavioural Sciences/Clinical Psychiatry. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2015. p. 300-23.

Li R, Ma X, Wang G, Yang J, Wang C. Why sex differences in schizophrenia? J Transl Neurosci (Beijing). 2016;1(1):37-42. PMid:29152382

Dickson H, Hedges E, Ma S, Cullen A, MacCabe J, Kempton M. Academic achievement and schizophrenia: A systematic metaanalysis. Psychol Med. 2020;50(12):1949-65. https://doi.org/10.1017/S0033291720002354 PMid:32684198 DOI: https://doi.org/10.1017/S0033291720002354

Davidson L, Schmutte T, Dinzeo T, Andres-Hyman R. Remission and recovery in schizophrenia: Practitioner and patient perspectives. Schizophr Bull. 2008;34(1):5-8. https://doi.org/10.1093/schbul/sbm122 PMid:17984297 DOI: https://doi.org/10.1093/schbul/sbm122

Vela J. Repurposing sigma-1 receptor ligands for COVID-19 therapy? Front Pharmacol. 2020;11:1716. https://doi.org/10.3389/fphar.2020.582310 PMid:33364957 DOI: https://doi.org/10.3389/fphar.2020.582310

Hoertel N, Sanchez-Rico M, Vernet R, Jannot A, Neuraz A, Blanco C. Observational study of haloperidol in hospitalized patients with COVID-19. PLoS One. 2021;16(2):e0247122. https://doi.org/10.1371/journal.pone.0247122 PMid:33606790 DOI: https://doi.org/10.1371/journal.pone.0247122

Gardner D, Murphy A, O’Donnel H, Centorrino F, Baldessarini R. International consensus study of antipsychotic dosing. Am J Psychiatry. 2010;167(6):686-93. https://doi.org/10.1176/appi.ajp.2009.09060802 PMid:20360319 DOI: https://doi.org/10.1176/appi.ajp.2009.09060802

Haack M, Hinze-Selch D, Fenzel T, Kraus T, Kuhn M, Schuld A, et al. Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: Effects of confounding factors and diagnosis. J Psychiatr Res. 1999;33(5):407-18. https://doi.org/10.1016/s0022-3956(99)00021-7 PMid:10504009 DOI: https://doi.org/10.1016/S0022-3956(99)00021-7

Li L. Challenges and priorities in responding to COVID-19 in inpatient psychiatry. Psychiatr Serv. 2020;71(6):624-6. https://doi.org/10.1176/appi.ps.202000166 PMid:32321388 DOI: https://doi.org/10.1176/appi.ps.202000166

CDC. Implementation of Mitigation Strategies for Communities with Local COVID-19 Transmission. Atlanta, Georgia, United States: CDC; 2020. Available from: https://www.cdc.gov/coronavirus/2019-ncov/downloads/community-mitigationstrategy.pdf [Last accessed on 2021 Aug 14].

Fond G, Pauly V, Leone M, Llorca P. Disparities in intensive care unit admission and mortality among patients with schizophrenia and COVID-19: A national cohort study. Schizophr Bull. 2020;47(3):624-34. https://doi.org/10.1093/schbul/sbaa158 PMid:33089862 DOI: https://doi.org/10.1093/schbul/sbaa158

Lee S, Yang J, Moon S, Yoo I, Ha E. Association between mental illness and COVID-19 susceptibility and clinical outcomes in South Korea: A nationwide cohort study. Lancet Psychiatry. 2020;7(12):1025-31. https://doi.org/10.1016/S2215-0366(20)30421-1 PMid:32950066 DOI: https://doi.org/10.1016/S2215-0366(20)30421-1

Wang Q, Xu R, Volkow N. Increased risk of COVID-19 infection and mortality in people with mental disorders: Analysis from electronic health records in the United States. World Psychiatry. 2021;20(1):124-30. https://doi.org/10.1002/wps.20806 PMid:33026219 DOI: https://doi.org/10.1002/wps.20806

Li Y, Shi J, Xia J, Duan J, Chen L, Yu X. Asymptomatic and symptomatic patients with non-severe Coronavirus disease (COVID-19) have similar clinical features and virological courses: A retrospective single center study. Front Microbiol. 2020;11:1570. https://doi.org/10.3389/fmicb.2020.01570. PMid:32754137 DOI: https://doi.org/10.3389/fmicb.2020.01570

Cheng JL, Huang C, Zhang GJ, Liu DW, Li P, Lu CY. Epidemiological characteristics of novel coronavirus pneumonia in Henan. Zhonghua Jie He He Hu Xi Za Zhi. 2020;43(4):327-31. https://doi.org/10.3760/cma.j.cn112147-20200222-00148 PMid:32118390

Wang D, Hu B, Hu C. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. https://doi.org/10.1001/jama.2020.1585 PMid:32031570 DOI: https://doi.org/10.1001/jama.2020.1585

Huang C, Wang Y, Li XL, Ren L, Zhao J, Hu Y. Clinical features of patients infected with 2019 novel Coronavirus in Wuhan, China. Lancet. 2020;395(15):497-506. https://doi.org/10.1016/S0140-6736(20)30183-5 PMid:31986264 DOI: https://doi.org/10.1016/S0140-6736(20)30183-5

Yang H, Yuan X, Zhijie L, Ling Y, Jing W. The clinical implication of dynamic hematological parameters in COVID-19: A retrospective study in Chongqing, China. Int J Gen Med. 2021;14:4073-80. https://doi.org/10.2147/IJGM.S321292 PMid:34354369 DOI: https://doi.org/10.2147/IJGM.S321292

Lanini S, Montaldo C, Nicastri E, Vairo F, Agrati D. COVID-19 disease-temporal analyses of complete blood count parameters over course of illness, and relationship to patient demographics and management outcomes in survivors and non-survivors: A longitudinal descriptive cohort study. PLoS One. 2020;15(12):e0244129. https://doi.org/10.1371/journal.pone.0244129 PMid:33370366 DOI: https://doi.org/10.1371/journal.pone.0244129

Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: A descriptive study. Lancet Infect Dis. 2020;20(4):425-34. https://doi.org/10.1016/S1473-3099(20)30086-4 PMid:32105637 DOI: https://doi.org/10.1016/S1473-3099(20)30086-4

Ma Y, Xu Q, Wang F, Ma X, Wang X. Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China. Microbes Infect. 2020;22(4-5):212-7. https://doi.org/10.1016/j.micinf.2020.04.011 PMid:32387682 DOI: https://doi.org/10.1016/j.micinf.2020.04.011

Monji A, Kato T, Kanba S. Cytokines and schizophrenia: Microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009;63(3):257-65. https://doi.org/10.1111/j.1440-1819.2009.01945.x PMid:19579286 DOI: https://doi.org/10.1111/j.1440-1819.2009.01945.x

Naudin J, Capo C, Giusano B, Mege J, Azorin J. A diferential role for interleukin-6 and tumor necrosis factor-a in schizophrenia? Schizophr Res. 1997;26:227-33. https://doi.org/10.1016/s0920-9964(97)00059-5 PMid:9323355 DOI: https://doi.org/10.1016/S0920-9964(97)00059-5

Kim YK, Myint AM, Verkerk R, Scharpe S, Steinbusch H. Cytokine changes and tryptophan metabolites in medication-naïve and medication-free schizophrenic patients. Neuropsychobiology. 2009;59(2):123-9. https://doi.org/10.1159/000213565 PMid:19390223 DOI: https://doi.org/10.1159/000213565

Luo Y, He H, Zhang J, Ou Y, Fan N. Changes in serum TNF α, IL-18, and IL-6 concentrations in patients with chronic schizophrenia at admission and at discharge. Compr Psychiatry. 2019;90:82-7. https://doi.org/10.1016/j.comppsych.2019.01.003 PMid:30782515 DOI: https://doi.org/10.1016/j.comppsych.2019.01.003

Mesa A, Cesar E, Martin-Montanez E, Alvarez E. Acute lung injury biomarkers in the prediction of COVID-19 severity: Total thiol, ferritin and lactate dehydrogenase. Antioxidants (Basel). 2021;10(8):1221. https://doi.org/10.3390/antiox10081221 PMid:34439469 DOI: https://doi.org/10.3390/antiox10081221

Hasbi M, Loebis B, Camelia V. Perbedaan Kadar Tumor Necrosis Factor-Alpha dan Kadar Interleukin-2 Pada Orang Dengan Skizofrenia Yang Mendapat Risperidon Pada Fase Akut Pengobatan di Rumah Sakit Jiwa Prof.dr.M.Ildrem Medan. Indonesia: North Sumatra University; 2020.

Muric N, Arsenijevic N, Borovcanin M. Chlorpromazine as a potential antipsychotic choice in COVID-19 treatment. Front Psychiatry. 2020;11:612347. https://doi.org/10.3389/fpsyt.2020.612347 PMid:33424669 DOI: https://doi.org/10.3389/fpsyt.2020.612347

Tsuneizumi T, Babb S, Cohen B. Drug distribution between blood and brainas a determinant of antipsychotic drug effects. Biol Psychiatry. 1992;32(9):817-24. https://doi.org/10.1016/0006-3223(92)90085-e PMid:1360262 DOI: https://doi.org/10.1016/0006-3223(92)90085-E

Procyshyn R, Bezchlibnyk-Butler KZ. In: Jeffries J, editor. Clinical Handbook of Psychotropic Drugs. 21st ed. Gottingen: Hogrefe Publishing; 2015. DOI: https://doi.org/10.1027/00474-000

Echeverría-Esnal D, Martin-Ontiyuelo C, Navarrete-Rouco M, Cusco M, Ferrandez O. Azithromycin in the treatment of COVID-19: A review. Expert Rev Anti Infect Ther. 2021;19(2):147-63. https://doi.org/10.1080/14787210.2020.1813024 PMid:32853038 DOI: https://doi.org/10.1080/14787210.2020.1813024

Lee N, Wong C, Chan M. Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial. Antiviral Res. 2017;144:48-56. https://doi.org/10.1016/j.antiviral.2017.05.008 PMid:28535933 DOI: https://doi.org/10.1016/j.antiviral.2017.05.008

Arshad S, Kilgore P, Chaudhry Z. Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19. Int J Infect Dis. 2020;97:396-403. https://doi.org/10.1016/j.ijid.2020.06.099 PMid:32623082 DOI: https://doi.org/10.1016/j.ijid.2020.06.099

Purwati, Miatmoko A, Nasronudin. An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia. PLoS One. 2021;16(6):e0252302. https://doi.org/10.1371/journal.pone.0252302 PMid:34143818 DOI: https://doi.org/10.1371/journal.pone.0252302

Meyerowitz E, Vannier A, Friesen M, Schoenfeld, Gelfand J, Callahan MV. Rethinking the role of hydroxychloroquine in the treatment of COVID-19. FASEB J. 2020;34(5):6027-37. https://doi.org/10.1096/fj.202000919 PMid:32350928 DOI: https://doi.org/10.1096/fj.202000919

Meng XY, Zhang HX, Mezei M, Cui M. A powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2011;7(2):146-57. https://doi.org/10.2174/157340911795677602 PMid:21534921 DOI: https://doi.org/10.2174/157340911795677602

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2021-12-27

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Tanra AJ, Andi Sameggu A, Renaldi R, Bahar B, Syamsuddin S, Ilyas M, Lisal ST. The Effectiveness of Chlorpromazine to Decrease the Level of Tumor Necrosis Factor-Alpha Serum in Schizophrenic Patients with Coronavirus Disease 2019. Open Access Maced J Med Sci [Internet]. 2021 Dec. 27 [cited 2024 Mar. 29];9(E):1606-1. Available from: https://oamjms.eu/index.php/mjms/article/view/7702

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