Safety of psychotropic medications in people with COVID-19: evidence review and practical recommendations

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Abstract

Background

The novel coronavirus pandemic calls for a rapid adaptation of conventional medical practices to meet the evolving needs of such vulnerable patients. People with coronavirus disease (COVID-19) may frequently require treatment with psychotropic medications, but are at the same time at higher risk for safety issues because of the complex underlying medical condition and the potential interaction with medical treatments.

Methods

In order to produce evidence-based practical recommendations on the optimal management of psychotropic medications in people with COVID-19, an international, multi-disciplinary working group was established. The methodology of the WHO Rapid Advice Guidelines in the context of a public health emergency and the principles of the AGREE statement were followed. Available evidence informing on the risk of respiratory, cardiovascular, infective, hemostatic, and consciousness alterations related to the use of psychotropic medications, and drug–drug interactions between psychotropic and medical treatments used in people with COVID-19, was reviewed and discussed by the working group.

Results

All classes of psychotropic medications showed potentially relevant safety risks for people with COVID-19. A set of practical recommendations was drawn in order to inform frontline clinicians on the assessment of the anticipated risk of psychotropic-related unfavorable events, and the possible actions to take in order to effectively manage this risk, such as when it is appropriate to avoid, withdraw, switch, or adjust the dose of the medication.

Conclusions

The present evidence-based recommendations will improve the quality of psychiatric care in people with COVID-19, allowing an appropriate management of the medical condition without worsening the psychiatric condition and vice versa.

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Most cited references 107

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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

Zunyou Wu, Jennifer M. McGoogan (2020)

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COVID-19: consider cytokine storm syndromes and immunosuppression

Puja Mehta, Daniel McAuley, Michael Brown … (2020)

As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, 1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. 2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections 3 and occurs in 3·7–4·3% of sepsis cases. 4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients. 5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α. 6 Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p 39·4°C 49 Organomegaly None 0 Hepatomegaly or splenomegaly 23 Hepatomegaly and splenomegaly 38 Number of cytopenias * One lineage 0 Two lineages 24 Three lineages 34 Triglycerides (mmol/L) 4·0 mmol/L 64 Fibrinogen (g/L) >2·5 g/L 0 ≤2·5 g/L 30 Ferritin ng/ml 6000 ng/ml 50 Serum aspartate aminotransferase <30 IU/L 0 ≥30 IU/L 19 Haemophagocytosis on bone marrow aspirate No 0 Yes 35 Known immunosuppression † No 0 Yes 18 The Hscore 11 generates a probability for the presence of secondary HLH. HScores greater than 169 are 93% sensitive and 86% specific for HLH. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of HLH. HScores can be calculated using an online HScore calculator. 11 HLH=haemophagocytic lymphohistiocytosis. * Defined as either haemoglobin concentration of 9·2 g/dL or less (≤5·71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. † HIV positive or receiving longterm immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine).

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Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

Ling Mao, Huijuan Jin, Mengdie Wang … (2020)

The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations.

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Author and article information

Contributors

Giovanni Ostuzzi:

ORCID: http://orcid.org/0000-0003-2248-9524

giovanni.ostuzzi@univr.it

Journal

Journal ID (nlm-ta): BMC Med

Journal ID (iso-abbrev): BMC Med

Title: BMC Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1741-7015

Publication date (Electronic): 15 July 2020

Publication date PMC-release: 15 July 2020

Publication date Collection: 2020

Volume: 18

Electronic Location Identifier: 215

Affiliations

[1 ]GRID grid.5611.3, ISNI 0000 0004 1763 1124, WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, , University of Verona, ; Verona, Italy

[2 ]GRID grid.440243.5, ISNI 0000 0004 0453 5950, Department of Psychiatry, , The Zucker Hillside Hospital, ; Northwell Health, Glen Oaks, NY USA

[3 ]GRID grid.9024.f, ISNI 0000 0004 1757 4641, Department of Molecular Medicine, , University of Siena, ; Siena, Italy

[4 ]GRID grid.11956.3a, ISNI 0000 0001 2214 904X, Department of Psychiatry, Faculty of Medicine and Health Sciences, , Stellenbosch University, ; Tygerberg Campus, Cape Town, 8000 South Africa

[5 ]Azienda ULSS 9 Scaligera, Verona, Italy

[6 ]GRID grid.26091.3c, ISNI 0000 0004 1936 9959, Department of Neuropsychiatry, , Keio University School of Medicine, ; Tokyo, Japan

[7 ]GRID grid.17089.37, Department of Psychiatry, , University of Alberta, ; Edmonton, Alberta Canada

[8 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, , King’s College London, ; London, UK

[9 ]Physiotherapy Department, South London and Maudsley National Health Services Foundation Trust, London, UK

[10 ]GRID grid.439833.6, ISNI 0000 0001 2112 9549, Pharmacy Department, , Maudsley Hospital, ; London, UK

[11 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Centre for Global Mental Health and Centre for Implementation Science, Institute of Psychiatry, Psychology and Neuroscience, , King’s College London, ; London, UK

[12 ]GRID grid.429098.e, School of Psychiatry, , UNSW Sydney and Schizophrenia Research Unit, Ingham Institute of Applied Medical Research, ; Liverpool, NSW Australia

[13 ]GRID grid.410607.4, Department of Psychiatry and Psychotherapy, , University Medical Center of Mainz, ; Mainz, Germany

[14 ]GRID grid.257060.6, ISNI 0000 0001 2284 9943, Department of Psychiatry and Molecular Medicine, , Zucker School of Medicine at Hofstra/Northwell, ; Hempstead, NY USA

[15 ]GRID grid.6363.0, ISNI 0000 0001 2218 4662, Department of Child and Adolescent Psychiatry, , Charité Universitätsmedizin Berlin, ; Berlin, Germany

Author information

Giovanni Ostuzzi http://orcid.org/0000-0003-2248-9524

Article

Publisher ID: 1685

DOI: 10.1186/s12916-020-01685-9

PMC ID: 7360478

PubMed ID: 32664944

SO-VID: b692eea0-318e-46c2-9672-80c7901e8307

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 14 May 2020

Date accepted : 28 June 2020

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: novel coronavirus,covid-19,psychopharmacology,psychiatric comorbidity,drug–drug interactions

Data availability:

ScienceOpen disciplines: Medicine

Keywords: novel coronavirus, covid-19, psychopharmacology, psychiatric comorbidity, drug–drug interactions