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BMC Medicine
Published in: BMC Medicine 1/2020

Open Access 01-12-2020 | Coronavirus | Research article

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

Authors: Giovanni Ostuzzi, Davide Papola, Chiara Gastaldon, Georgios Schoretsanitis, Federico Bertolini, Francesco Amaddeo, Alessandro Cuomo, Robin Emsley, Andrea Fagiolini, Giuseppe Imperadore, Taishiro Kishimoto, Giulia Michencigh, Michela Nosé, Marianna Purgato, Serdar Dursun, Brendon Stubbs, David Taylor, Graham Thornicroft, Philip B. Ward, Christoph Hiemke, Christoph U. Correll, Corrado Barbui

Published in: BMC Medicine | Issue 1/2020

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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.
Appendix
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Literature
1.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020. https://​doi.​org/​10.​1001/​jama.​2020.​2648. Online ahead of print.
2.
3.
4.
5.
Jin Y-H, Cai L, Cheng Z-S, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Military Medical Research. 2020;7(1):4.PubMedPubMedCentralCrossRef
6.
7.
8.
Grabias B, Kumar S. Adverse neuropsychiatric effects of antimalarial drugs. Expert Opin Drug Saf. 2016;15(7):903–10.PubMedCrossRef
9.
Hansen BA, Greenberg KS, Richter JA. Ganciclovir-induced psychosis. N Engl J Med. 1996;335(18):1397.PubMedCrossRef
10.
Kong X, Zheng K, Tang M, et al. Prevalence and factors associated with depression and anxiety of hospitalized patients with COVID-19. medRxiv. 2020:2020.2003.2024.20043075.
11.
12.
Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091.PubMedPubMedCentralCrossRef
13.
14.
15.
16.
Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565–75.PubMedCrossRef
17.
Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci. 2020;11(7):995–8.PubMedCrossRef
18.
Barbui C, Bighelli I, Carrà G, Castellazzi M, Lucii C, Martinotti G, Nosè M, Ostuzzi G, STAR NETWORK INVESTIGATORS. Antipsychotic dose mediates the association between polypharmacy and corrected QT interval. PLoS One. 2016;11(2):e0148212.PubMedPubMedCentralCrossRef
19.
20.
Bindraban AN, Rolvink J, Berger FA, van den Bemt P, Kuijper AFM, van der Hoeven RTM, Mantel-Teeuwisse AK, Becker ML. Development of a risk model for predicting QTc interval prolongation in patients using QTc-prolonging drugs. Int J Clin Pharm. 2018;40(5):1372–9.PubMedCrossRef
21.
Brandt J, Leong C. Benzodiazepines and Z-drugs: an updated review of major adverse outcomes reported on in epidemiologic research. Drugs R D. 2017;17(4):493–507.PubMedPubMedCentralCrossRef
22.
Casini A, Alberio L, Angelillo-Scherrer A, et al. Thromboprophylaxis and laboratory monitoring for in-hospital patients with COVID-19 - a Swiss consensus statement by the Working Party Hemostasis. Swiss Med Wkly. 2020;150:w20247.PubMed
23.
Clegg A, Young JB. Which medications to avoid in people at risk of delirium: a systematic review. Age Ageing. 2011;40(1):23–9.PubMedCrossRef
24.
Correll CU, Detraux J, De Lepeleire J, De Hert M. Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry. 2015;14(2):119–36.PubMedPubMedCentralCrossRef
25.
26.
27.
de Leon J, Sanz EJ, Norén GN, De Las Cuevas C. Pneumonia may be more frequent and have more fatal outcomes with clozapine than with other second-generation antipsychotics. World Psychiatry. 2020;19(1):120–1.PubMedPubMedCentralCrossRef
28.
Deidda A, Pisanu C, Micheletto L, Bocchetta A, Del Zompo M, Stochino ME. Interstitial lung disease induced by fluoxetine: systematic review of literature and analysis of Vigiaccess, Eudravigilance and a national pharmacovigilance database. Pharmacol Res. 2017;120:294–301.PubMedCrossRef
29.
30.
Dragioti E, Solmi M, Favaro A, et al. Association of antidepressant use with adverse health outcomes: a systematic umbrella review. JAMA Psychiatry. 2019;76(12):1241–55.CrossRefPubMedPubMedCentral
31.
32.
Dzahini O, Singh N, Taylor D, Haddad PM. Antipsychotic drug use and pneumonia: systematic review and meta-analysis. J Psychopharmacol. 2018;32(11):1167–81.PubMedCrossRef
33.
Ekström MP, Bornefalk-Hermansson A, Abernethy AP, Currow DC. Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study. BMJ. 2014;348:g445.PubMedPubMedCentralCrossRef
34.
35.
Feng G, Zheng KI, Yan QQ, Rios RS, Targher G, Byrne CD, Poucke SV, Liu WY, Zheng MH. COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies. J Clin Transl Hepatol. 2020;8(1):18–24.PubMedPubMedCentralCrossRef
36.
Flanagan RJ, Dunk L. Haematological toxicity of drugs used in psychiatry. Hum Psychopharmacol. 2008;23(Suppl 1):27–41.PubMedCrossRef
37.
Foisy MM, Yakiwchuk EM, Hughes CA. Induction effects of ritonavir: implications for drug interactions 2008; 42(7–8):1048–1059.
38.
Gałecki P, Mossakowska-Wójcik J, Talarowska M. The anti-inflammatory mechanism of antidepressants - SSRIs, SNRIs. Prog Neuropsychopharmacol Biol Psychiatry. 2018;80(Pt C):291–4.PubMedCrossRef
39.
Galling B, Roldán A, Hagi K, et al. Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis. World Psychiatry. 2017;16(1):77–89.PubMedPubMedCentralCrossRef
40.
41.
Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J. 2013;13(2):214–23.PubMedPubMedCentral
42.
43.
44.
Hasnain M, Vieweg WV. QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review. CNS Drugs. 2014;28(10):887–920.PubMedCrossRef
45.
Hiemke C, Bergemann N, Clement HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry. 2018;51(1–02):e1.PubMed
46.
Hiemke C, Pfuhlmann B. Interactions and monitoring of antipsychotic drugs. Handb Exp Pharmacol. 2012;212:241–65.CrossRef
47.
Howland RH. More on antidepressant drugs and infectious disease. J Psychosoc Nurs Ment Health Serv. 2013;51(10):11–3.PubMedCrossRef
48.
Huhn M, Nikolakopoulou A, Schneider-Thoma J, et al. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019;394(10202):939–51.PubMedPubMedCentralCrossRef
49.
Hui D. Benzodiazepines for agitation in patients with delirium: selecting the right patient, right time, and right indication. Curr Opin Support Palliat Care. 2018;12(4):489–94.PubMedPubMedCentralCrossRef
50.
51.
Kaplan J, Schwartz AC, Ward MC. Clozapine-associated aspiration pneumonia: case series and review of the literature. Psychosomatics. 2018;59(2):199–203.PubMedCrossRef
52.
Kirmeier E, Eriksson LI, Lewald H, et al. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study. Lancet Respir Med. 2019;7(2):129–40.PubMedCrossRef
53.
Köhler CA, Freitas TH, Stubbs B, et al. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol. 2018;55(5):4195–206.PubMed
54.
Kubera M, Lin AH, Kenis G, Bosmans E, van Bockstaele D, Maes M. Anti-inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. J Clin Psychopharmacol. 2001;21(2):199–206.PubMedCrossRef
55.
Kunutsor SK, Seidu S, Khunti K. Depression, antidepressant use, and risk of venous thromboembolism: systematic review and meta-analysis of published observational evidence. Ann Med. 2018;50(6):529–37.PubMedCrossRef
56.
Lader M, Kyriacou A. Withdrawing benzodiazepines in patients with anxiety disorders. Curr Psychiatry Rep. 2016;18(1):8.PubMedCrossRef
57.
Lal LS, Zhuang A, Hung F, Feng C, Arbuckle R, Fisch MJ. Evaluation of drug interactions in patients treated with antidepressants at a tertiary care cancer center. Support Care Cancer. 2012;20(5):983–9.PubMedCrossRef
58.
Levin GM, DeVane CL. A review of cyclic antidepressant-induced blood dyscrasias. Ann Pharmacother. 1992;26(3):378–83.PubMedCrossRef
59.
Lu XM, Zhu JP, Zhou XM. The effect of benzodiazepines on insomnia in patients with chronic obstructive pulmonary disease: a meta-analysis of treatment efficacy and safety. Int J Chron Obstruct Pulmon Dis. 2016;11:675–85.PubMedPubMedCentralCrossRef
60.
May M, Beauchemin M, Vary C, Barlow D, Houseknecht KL. The antipsychotic medication, risperidone, causes global immunosuppression in healthy mice. PLoS One. 2019;14(6):e0218937.PubMedPubMedCentralCrossRef
61.
62.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–4.PubMedPubMedCentralCrossRef
63.
Misra DP, Agarwal V, Gasparyan AY, Zimba O. Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets. Clin Rheumatol. 2020.
64.
Molanaei H, Qureshi AR, Heimbürger O, Lindholm B, Diczfalusy U, Anderstam B, Bertilsson L, Stenvinkel P. Inflammation down-regulates CYP3A4-catalysed drug metabolism in hemodialysis patients. BMC Pharmacol Toxicol. 2018;19(1):33.PubMedPubMedCentralCrossRef
65.
Morgan ET. Impact of infectious and inflammatory disease on cytochrome P450-mediated drug metabolism and pharmacokinetics. Clin Pharmacol Ther. 2009;85(4):434–8.PubMedCrossRef
66.
Murru A, Popovic D, Pacchiarotti I, Hidalgo D, León-Caballero J, Vieta E. Management of adverse effects of mood stabilizers. Curr Psychiatry Rep. 2015;17(8):603.PubMedCrossRef
67.
68.
Nooijen PM, Carvalho F, Flanagan RJ. Haematological toxicity of clozapine and some other drugs used in psychiatry. Hum Psychopharmacol. 2011;26(2):112–9.PubMedCrossRef
69.
Ostinelli EG, Brooke-Powney MJ, Li X, Adams CE. Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database Syst Rev. 2017;7(7):Cd009377.PubMed
70.
Papola D, Ostuzzi G, Gastaldon C, et al. Antipsychotic use and risk of life-threatening medical events: umbrella review of observational studies. Acta Psychiatr Scand. 2019;140(3):227–43.PubMedCrossRef
71.
Polcwiartek C, Sneider B, Graff C, Taylor D, Meyer J, Kanters JK, Nielsen J. The cardiac safety of aripiprazole treatment in patients at high risk for torsade: a systematic review with a meta-analytic approach. Psychopharmacology. 2015;232(18):3297–308.PubMedCrossRef
72.
Pollok J, van Agteren JE, Carson-Chahhoud KV. Pharmacological interventions for the treatment of depression in chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018;12(12):Cd012346.PubMed
73.
Ponsford M, Castle D, Tahir T, et al. Clozapine is associated with secondary antibody deficiency. Br J Psychiatry. 2018;214(2):1–7.
74.
75.
Rochester MP, Kane AM, Linnebur SA, Fixen DR. Evaluating the risk of QTc prolongation associated with antidepressant use in older adults: a review of the evidence. Ther Adv Drug Saf. 2018;9(6):297–308.PubMedPubMedCentralCrossRef
76.
Røge R, Møller BK, Andersen CR, Correll CU, Nielsen J. Immunomodulatory effects of clozapine and their clinical implications: what have we learned so far? Schizophr Res. 2012;140(1–3):204–13.PubMedCrossRef
77.
Romeo B, Brunet-Lecomte M, Martelli C, Benyamina A. Kinetics of cytokine levels during antipsychotic treatment in schizophrenia: a meta-analysis. Int J Neuropsychopharmacol. 2018;21(9):828–36.PubMedPubMedCentralCrossRef
78.
Schneider-Thoma J, Efthimiou O, Bighelli I, et al. Second-generation antipsychotic drugs and short-term somatic serious adverse events: a systematic review and meta-analysis. Lancet Psychiatry. 2019;6(9):753–65.PubMedCrossRef
79.
Schwartz PJ, Woosley RL. Predicting the unpredictable: drug-induced QT prolongation and torsades de pointes. J Am Coll Cardiol. 2016;67(13):1639–50.PubMedCrossRef
80.
Shah FA, Girard TD, Yende S. Limiting sedation for patients with acute respiratory distress syndrome - time to wake up. Curr Opin Crit Care. 2017;23(1):45–51.PubMedPubMedCentralCrossRef
81.
Stapel B, Sieve I, Falk CS, Bleich S, Hilfiker-Kleiner D, Kahl KG. Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells. J Psychiatr Res. 2018;105:95–102.PubMedCrossRef
82.
Sultana J, Calabró M, Garcia-Serna R, Ferrajolo C, Crisafulli C, Mestres J, Trifirò G. Biological substantiation of antipsychotic-associated pneumonia: systematic literature review and computational analyses. PLoS One. 2017;12(10):e0187034.PubMedPubMedCentralCrossRef
83.
Sun GQ, Zhang L, Zhang LN, Wu Z, Hu DF. Benzodiazepines or related drugs and risk of pneumonia: a systematic review and meta-analysis. Int J Geriatr Psychiatry. 2019;34(4):513–21.PubMedCrossRef
84.
Szałach ŁP, Lisowska KA, Cubała WJ. The influence of antidepressants on the immune system. Arch Immunol Ther Exp. 2019;67(3):143–51.CrossRef
85.
Takeuchi H, Suzuki T, Remington G, Uchida H. Antipsychotic polypharmacy and corrected QT interval: a systematic review. Can J Psychiatr. 2015;60(5):215–22.CrossRef
86.
Terpos E, Ntanasis-Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, Psaltopoulou T, Gerotziafas G, Dimopoulos MA. Hematological findings and complications of COVID-19. Am J Hematol. 2020;95(7):834–47. https://​doi.​org/​10.​1002/​ajh.​25829. Epub 2020 May 23.
87.
Vandael E, Vandenberk B, Vandenberghe J, Willems R, Foulon V. Risk factors for QTc-prolongation: systematic review of the evidence. Int J Clin Pharm. 2017;39(1):16–25.PubMedCrossRef
88.
Vozoris NT, Fischer HD, Wang X, et al. Benzodiazepine drug use and adverse respiratory outcomes among older adults with COPD. Eur Respir J. 2014;44(2):332–40.PubMedCrossRef
89.
90.
Wang MT, Tsai CL, Lin CW, Yeh CB, Wang YH, Lin HL. Association between antipsychotic agents and risk of acute respiratory failure in patients with chronic obstructive pulmonary disease. JAMA Psychiatry. 2017;74(3):252–60.PubMedCrossRef
91.
92.
93.
Wiciński M, Węclewicz MM. Clozapine-induced agranulocytosis/granulocytopenia: mechanisms and monitoring. Curr Opin Hematol. 2018;25(1):22–8.PubMedCrossRef
94.
95.
Wu YC, Tseng PT, Tu YK, et al. Association of delirium response and safety of pharmacological interventions for the management and prevention of delirium: a network meta-analysis. JAMA Psychiatry. 2019;76(5):526–35.PubMedPubMedCentralCrossRef
96.
97.
98.
99.
100.
101.
102.
103.
Siccardi M, Marzolini C, Seden K, Almond L, Kirov A, Khoo S, Owen A, Back D. Prediction of drug-drug interactions between various antidepressants and efavirenz or boosted protease inhibitors using a physiologically based pharmacokinetic modelling approach. Clin Pharmacokinet. 2013;52(7):583–92.PubMedCrossRef
104.
Li SA, Alexander PE, Reljic T, Cuker A, Nieuwlaat R, Wiercioch W, Guyatt G, Schünemann HJ, Djulbegovic B. Evidence to decision framework provides a structured “roadmap” for making GRADE guidelines recommendations. J Clin Epidemiol. 2018;104:103–12.PubMedPubMedCentralCrossRef
105.
Ostuzzi G, Turrini G, Gastaldon C, Papola D, Rayner L, Caruso R, Grassi L, Hotopf M, Barbui C. Efficacy and acceptability of antidepressants in patients with ischemic heart disease: systematic review and meta-analysis. Int Clin Psychopharmacol. 2019;34(2):65–75.PubMedCrossRef
106.
Adhikari SP, Meng S, Wu YJ, et al. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infect Dis Poverty. 2020;9(1):29.PubMedPubMedCentralCrossRef
107.
Torbic H, Duggal A. Antipsychotics, delirium, and acute respiratory distress syndrome: what is the link? Pharmacotherapy. 2018;38(4):462–9.PubMedCrossRef
108.
Jönsson AK, Schill J, Olsson H, Spigset O, Hägg S. Venous thromboembolism during treatment with antipsychotics: a review of current evidence. CNS Drugs. 2018;32(1):47–64.PubMedPubMedCentralCrossRef
109.
Fanelli V, Fiorentino M, Cantaluppi V, Gesualdo L, Stallone G, Ronco C, Castellano G. Acute kidney injury in SARS-CoV-2 infected patients. Crit Care. 2020;24(1):155.PubMedPubMedCentralCrossRef
110.
Piano S, Dalbeni A, Vettore E, et al. Abnormal liver function tests predict transfer to intensive care unit and death in COVID-19. Liver Int. 2020.
111.
112.
Lembke A, Papac J, Humphreys K. Our other prescription drug problem. N Engl J Med. 2018;378(8):693–5.PubMedCrossRef
113.
Barbui C, Purgato M, Abdulmalik J, et al. Efficacy of psychosocial interventions for mental health outcomes in low-income and middle-income countries: an umbrella review. Lancet Psychiatry. 2020;7(2):162–72.PubMedCrossRef
114.
115.
van Ginneken N, Tharyan P, Lewin S, Rao GN, Meera SM, Pian J, Chandrashekar S, Patel V. Non-specialist health worker interventions for the care of mental, neurological and substance-abuse disorders in low- and middle-income countries. Cochrane Database Syst Rev. 2013;(11):CD009149. https://​doi.​org/​10.​1002/​14651858.​CD009149.​pub2.
116.
117.
Metadata
Title
Safety of psychotropic medications in people with COVID-19: evidence review and practical recommendations
Authors
Giovanni Ostuzzi
Davide Papola
Chiara Gastaldon
Georgios Schoretsanitis
Federico Bertolini
Francesco Amaddeo
Alessandro Cuomo
Robin Emsley
Andrea Fagiolini
Giuseppe Imperadore
Taishiro Kishimoto
Giulia Michencigh
Michela Nosé
Marianna Purgato
Serdar Dursun
Brendon Stubbs
David Taylor
Graham Thornicroft
Philip B. Ward
Christoph Hiemke
Christoph U. Correll
Corrado Barbui
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2020
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-020-01685-9

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