Download PDF
Pharmacopsychiatry 2022; 55(01): 30-39
DOI: 10.1055/a-1559-3904
Original Paper

Impact of Psychiatric and Related Somatic Medications on the Duration and Severity of COVID-19: A Retrospective Explorative Multi-center Study from the German Metropolitan Ruhr-area

Udo Bonnet
1   Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Evangelisches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University of Duisburg-Essen, Essen, Germany
2   LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany
,
BenediktBernd Claus
1   Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Evangelisches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University of Duisburg-Essen, Essen, Germany
3   PedScience, Datteln, Germany
,
Martin Schaefer
4   Department of Psychiatry, Psychotherapy, Psychoso-matics and Addiction Medicine, Evangelische Kliniken Essen-Mitte, Essen, Germany
,
Jens Kuhn
5   Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Johanniter Hospital Oberhausen, Oberhausen, Germany
,
Peter Nyhuis
6   St. Marien-Hospital Eickel, Herne, Germany
,
Norbert Scherbaum
2   LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany
,
Martin Brüne
7   Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Bochum, Germany
,
Velat Wakili
4   Department of Psychiatry, Psychotherapy, Psychoso-matics and Addiction Medicine, Evangelische Kliniken Essen-Mitte, Essen, Germany
,
Georg Juckel
7   Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Bochum, Germany
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Introduction Several psychiatric and somatic medications are assumed to improve COVID-19-symptoms. These include antidepressants, antipsychotics, and anticonvulsants as well as anticoagulants, statins, and renin-angiotensin-aldosterone-system (RAAS)-inhibitors for somatic comorbid conditions. All these agents may reduce the hyperinflammatory response to SARS/CoV-2 or the related negative cardio-cerebrovascular outcomes.

Methods In a retrospective longitudinal, multi-center inpatient study, we sought to explore the influence of psychiatric medications on COVID-19, comprising the period from diagnosing SARS/CoV-2-infection via PCR (nasopharyngeal swab) up to the next 21 days. Ninety-six psychiatric inpatients (mean age [SD] 65.5 (20.1), 54% females) were included. The primary outcome was the COVID-19-duration. Secondary outcomes included symptom severity and the presence of residual symptoms.

Results COVID-19-related symptoms emerged in 60 (62.5%) patients, lasting 6.5 days on average. Six (6.3%) 56–95 years old patients died from or with COVID-19. COVID-19-duration and residual symptom-presence (n=22, 18%) were not significantly related to any substance. Respiratory and neuro-psychiatric symptom-load was significantly and negatively related to prescription of antidepressants and anticoagulants, respectively. Fatigue was negatively and positively related to RAAS-inhibitors and proton-pump-inhibitors, respectively. These significant relationships disappeared with p-value adjustment owed to multiple testing. The mean total psychiatric burden was not worsened across the study.

Discussion None of the tested medications was significantly associated with the COVID-19-duration and -severity up to the end of post-diagnosing week 3. However, there were a few biologically plausible and promising relationships with antidepressants, anticoagulants, and RAAS-inhibitors before p-value adjustment. These should encourage larger and prospective studies to re-evaluate the influence of somatic and psychiatric routine medications on COVID-19-related health outcomes.

Key words

antidepressants - antipsychotics - anticonvusants - anticoagulants - RAAS-inhibitors


Publication History

Received: 27 June 2021
Received: 14 July 2021

Accepted: 20 July 2021

Article published online:
16 September 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Miners S, Kehoe PG, Love S. Cognitive impact of COVID-19: Looking beyond the short term. Alzheimers Res Ther 2020; 12: 170
    CrossrefPubMedGoogle Scholar
  • 2 Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020; 323: 1239-1242
    CrossrefPubMedGoogle Scholar
  • 3 Chugh H, Awasthi A, Agarwal Y. et al. A comprehensive review on potential therapeutics interventions for COVID-19. Eur J Pharmacol 2021; 890: 173741
    CrossrefPubMedGoogle Scholar
  • 4 Feldt T, Karagiannidis C, Mager S. et al. Welche Rolle spielt ein mögliches Hyperinflammationssyndrom bei einer schweren COVID-19-Infektion und können hieraus Konsequenzen für die Therapie gezogen werden? Erfahrungen im Umgang mit COVID-19-Erktankten-Hinweise von Klinikern für Kliniker-Stand: 07/27/2020. doi. 10.25646/7037; accessed at 06/27/2021
    PubMed
  • 5 Henderson LA, Canna SW, Schulert GS. et al. On the alert for cytokine storm: Immunopathology in COVID-19. Arthritis Rheumatol 2020; 72: 1059-1063
    CrossrefPubMedGoogle Scholar
  • 6 Cavalli G, Larcher A, Tomelleri A. et al. Interleukin-1 and interleukin-6 inhibition compared with standard management in patients with COVID-19 and hyperinflammation: a cohort study. Lancet Rheumatol 2021; 3: e253-e261
    CrossrefPubMedGoogle Scholar
  • 7 Scavone C, Mascolo A, Rafaniello C. et al. Therapeutic strategies to fight COVID-19: Which is the status artis? Br J Pharmacol 2021; doi: 10.1111/bph.15452. Epub ahead of print
    PubMed
  • 8 Eyre HA, Lavretsky H, Kartika J. et al. Modulatory effects of antidepressant classes on the innate and adaptive immune system in depression. Pharmacopsychiatry 2016; 49: 85-96
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Szałach ŁP, Lisowska KA, Cubała WJ. The influence of antidepressants on the immune system. Arch Immunol Ther Exp (Warsz) 2019; 67: 143-151
    CrossrefPubMedGoogle Scholar
  • 10 Dinesh AA, Islam J, Khan J. et al. Effects of antipsychotic drugs: Cross talk between the nervous and innate immune system. CNS Drugs. 2020; 34: 1229-1251
    CrossrefPubMedGoogle Scholar
  • 11 Lenze EJ, Mattar C, Zorumski CF. et al. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: A randomized clinical trial. JAMA 2020; 324: 2292-2300
    CrossrefPubMedGoogle Scholar
  • 12 Schloer S, Brunotte L, Goretzko J. et al. Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine. Emerg Microbes Infect 2020; 9: 2245-2255
    CrossrefPubMedGoogle Scholar
  • 13 Hoertel N, Sánchez-Rico M, Vernet R. et al. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: Results from an observational study. Mol Psychiatry 2021; doi: 10.1038/s41380-021-01021-4. Epub ahead of print
    PubMed
  • 14 Hoertel N, Sánchez-Rico M, Gulbins E. et al. Association between FIASMAs and reduced risk of intubation or death in individuals hospitalized for severe COVID-19: An observational multicenter study. Clin Pharmacol Ther 2021; doi: 10.1002/cpt.2317. Epub ahead of print
    PubMed
  • 15 Wang J, Pendurthi UR, Rao LVM. Acid sphingomyelinase plays a critical role in LPS- and cytokine-induced tissue factor procoagulant activity. Blood 2019; 134: 645-655
    CrossrefPubMedGoogle Scholar
  • 16 Bonnet U, Juckel G, Scherbaum N. et al. Are persons treated with antidepressants and/or antipsychotics possibly better protected against severe COVID 19?. Pharmacopsychiatry 2021; 54: 142-143
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Hoertel N, Sánchez-Rico M, Vernet R. et al. Observational study of haloperidol in hospitalized patients with COVID-19. PLoS One 2021; 16: e0247122
    CrossrefPubMedGoogle Scholar
  • 18 Hoertel N, Sánchez-Rico M, Vernet R. et al. Observational study of chlorpromazine in hospitalized patients with COVID-19. Clin Drug Investig; 41: 221-233
    PubMed
  • 19 Bonnet U, Knierim U, Ronge R. et al. Late-onset polyserositis emerging during long-term clozapine treatment and persisting after clozapine discontinuation: Is clozapine really innocent? J Clin Psychopharmacol 2021. Epub ahead of print
    PubMed
  • 20 Clark SR, Warren NS, Kim G. et al. Elevated clozapine levels associated with infection: A systematic review. Schizophr Res 2018; 192: 50-56
    CrossrefPubMedGoogle Scholar
  • 21 de Leon J, Sanz EJ, Norén N. et al. Pneumonia may be more frequent and have more fatal outcomes with clozapine than with other second-generation antipsychotics. World Psychiatry 2020; 19: 120
    CrossrefPubMedGoogle Scholar
  • 22 Govind R, Fonseca de Freitas D. et al. Clozapine treatment and risk of COVID-19 infection: Retrospective cohort study. Br J Psychiatry 2020; doi: 10.1192/bjp.2020.151. Epub ahead of print
    PubMed
  • 23 Nadkarni GN, Lala A, Bagiella E. et al. Anticoagulation, bleeding, mortality, and pathology in hospitalized patients with COVID-19. J Am Coll Cardiol 2020; 76: 1815-1826
    CrossrefPubMedGoogle Scholar
  • 24 Magro G. COVID-19: Review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking. Virus Res 2020; 286: 198070
    CrossrefPubMedGoogle Scholar
  • 25 Wang JJ, Edin ML, Zeldin DC. et al. Good or bad: application of RAAS inhibitors in COVID-19 patients with cardiovascular comorbidities. Pharmacol Ther 2020; 215: 107628
    CrossrefPubMedGoogle Scholar
  • 26 Malhotra A, Hepokoski M, McCowen KC. et al. Metformin and COVID-19. iScience. 2020; 23: 101425
    CrossrefPubMedGoogle Scholar
  • 27 Rodrigues-Diez RR, Tejera-Muñoz A, Marquez-Exposito L. et al. Statins: Could an old friend help in the fight against COVID-19?. Br J Pharmacol 2020; 177: 4873-4886
    CrossrefPubMedGoogle Scholar
  • 28 Almario CV, Chey WD, Spiegel BMR. Increased risk of covid-19 among users of proton pump inhibitors. Am J Gastroenterol 2020; 115: 1707-1715
    CrossrefPubMedGoogle Scholar
  • 29 Pranata R, Huang I, Lawrensia S, Henrina J. et al. Proton pump inhibitor on susceptibility to COVID-19 and its severity: A systematic review and meta-analysis. Pharmacol Rep 2021; doi: 10.1007/s43440-021-00263-x. Epub ahead of print
    PubMed
  • 30 Nemani K, Li C, Olfson M, Blessing EM. et al. Association of psychiatric disorders with mortality among patients with COVID-19. JAMA Psychiatry 2021; 78: 380-386
    CrossrefPubMedGoogle Scholar
  • 31 Wang Q, Xu R, Volkow ND. 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: 124-130
    CrossrefPubMedGoogle Scholar
  • 32 Xiong GL, Atkin A, Moquin K. et al. COVID-19 transmission in a psychiatric long-term care rehabilitation facility: An observational study. Prim Care Companion CNS Disord 2020; 22: 20m02765
    CrossrefPubMedGoogle Scholar
  • 33 Budweiser S, Baş Ş, Jörres RA. et al. Comparison of the first and second waves of hospitalized patients with SARS-CoV-2. Dtsch Arztebl Int 2021; 118: 326-327
    CrossrefPubMedGoogle Scholar
  • 34 Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont) 2007; 4: 28-37
    PubMedGoogle Scholar
  • 35 DeBruine LM, Barr DJ. Understanding mixed-effects models through data simulation. Adv Methods Practices Psychological Sci 2021; 4: 1-15
    CrossrefPubMedGoogle Scholar
  • 36 Finch WH, Bolin JE, Kelley K. Multilevel Modeling Using R (2nd ed.). Chapman & Hall/CRC Statistics in the Social and Behavioral Sciences Series. Boca Raton, Florida: CRC Press; 2019
  • 37 R Core Team. R: A language and environment for statistical computing (Version 4.0.3) [Computer software]. Vienna 2020, Austria. https://www.R-project.org/; accessed on 06/27/2021
    PubMed
  • 38 RStudio Team. RStudio: Integrated development environment for R (Version 1.4.1087) [Computer software]. Boston 2020, MA. http://www.rstudio.com; accessed at 06/27/2021
    PubMed
  • 39 Wickham H, Averick M, Bryan J. et al. Welcome to the Tidyverse. J Open Source Software 2019; 4: 1686
    CrossrefPubMedGoogle Scholar
  • 40 Bates D, Mächler M, Bolker B. et al. Fitting linear mixed-effects models using lme4. J Stat Softw 2015; 67: 1-48
    CrossrefPubMedGoogle Scholar
  • 41 Kuznetsova A, Brockhoff PB, Christensen RHB. lmerTest Package: tests in linear mixed effects models. J Stat Softw 2017; 82. doi: 10.18637/jss.v082.i13 accessed at 06/27/2021
    PubMed
  • 42 Giesbrecht FG, Burns JC. Two-stage analysis based on a mixed model: large-sample asymptotic theory and small-sample simulation results. Biometrics 1985; 41: 477. doi: 10.2307/2530872; accessed at 06/27/2021
    PubMed
  • 43 Hrong-Tai Fai A, Cornelius PL. Approximate F-tests of multiple degree of freedom hypotheses in generalized least squares analyses of unbalanced split-plot experiments. J Stat Comput Simul 1996; 54: 363–378. doi: 10.1080/00949659608811740; accessed on 06/27/2021
    PubMed
  • 44 Benjamini Y, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 1995; 57: 289–300 doi: 10.1111/J.2517-6161.1995.TB02031.X; accessed on 06/27/2021
    PubMed
  • 45 Williamson EJ, Walker AJ, Bhaskaran K. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020; 584: 430-436
    CrossrefPubMedGoogle Scholar
  • 46 Chatterjee NA, Jensen PN, Harris AW. et al. Admission respiratory status predicts mortality in COVID-19. Influenza Other Respir Viruses 2021; doi: 10.1111/irv.12869. Epub ahead of print
    PubMed
  • 47 Zeitler S, Ye L, Andreyeva A, Schumacher F. et al. Acid sphingomyelinase-a regulator of canonical transient receptor potential channel 6 (TRPC6) activity. J Neurochem 2019; 150: 678-690
    CrossrefPubMedGoogle Scholar
  • 48 Bonnet U, Bingmann D, Wiltfang J. et al. Modulatory effects of neuropsychopharmaca on intracellular pH of hippocampal neurones in vitro. Br J Pharmacol 2010; 159: 474-483 DOI: 10.1111/j.1476-5381.2009.00540.x.
    CrossrefPubMedGoogle Scholar
  • 49 Bonnet U. The sour side of vitamin C might mediate neuroprotective, anticonvulsive and antidepressant-like effects. Med Hypotheses 2019; 131: 109320
    CrossrefPubMedGoogle Scholar
  • 50 Spuch C, López-García M, Rivera-Baltanás T. et al. Does lithium deserve a place in the treatment against COVID-19? A preliminary observational study in six patients, case report. Front Pharmacol 2020; 11: 557629
    CrossrefPubMedGoogle Scholar
  • 51 Nassar A, Azab AN. Effects of lithium on inflammation. ACS Chem Neurosci 2014; 5: 451-458
    CrossrefPubMedGoogle Scholar
  • 52 Castillo R, Quizon G, Juco M. et al. Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series. Melatonin Research 2020; 3: 297-310
    CrossrefPubMedGoogle Scholar
  • 53 Huang Y, Pinto MD, Borelli JL. et al. COVID symptoms, symptom clusters, and predictors for becoming a long-hauler: Looking for clarity in the haze of the pandemic. medRxiv [Preprint] 2021: 2021.03.03.21252086. doi: 10.1101/2021.03.03.21252086
    PubMed
  • 54 Wang X, Kattan MW. Cohort studies: Design, analysis, and reporting. Chest 2020; 158: S72-S78
    CrossrefPubMedGoogle Scholar
  • 55 Stengel A, Malek N, Zipfel S. et al. Long haulers—what is the evidence for post-COVID fatigue?. Front Psychiatry 2021; 12: 677934
    CrossrefPubMedGoogle Scholar