Relation of severe COVID-19 to polypharmacy and prescribing of psychotropic drugs: the REACT-SCOT case-control study
Paul M Mckeigue, Sharon Kennedy, Amanda Weir, Jen Bishop, Stuart J Mcgurnaghan, David Mcallister, Chris Robertson, Rachael Wood, Nazir Lone, Janet Murray, Thomas M Caparrotta, Alison Smith-Palmer, David Goldberg, Jim Mcmenamin, Bruce Guthrie, Sharon Hutchinson, Helen M Colhoun
BMC Medicine, doi:10.1186/s12916-021-01907-8
Background: The objective of this study was to investigate the relation of severe COVID-19 to prior drug prescribing. Methods: Severe cases were defined by entry to critical care or fatal outcome. For this matched case-control study (REACT-SCOT), all 4251 cases of severe COVID-19 in Scotland since the start of the epidemic were matched for age, sex and primary care practice to 36,738 controls from the population register. Records were linked to hospital discharges since June 2015 and dispensed prescriptions issued in primary care during the last 240 days. Results: Severe COVID-19 was strongly associated with the number of non-cardiovascular drug classes dispensed. This association was strongest in those not resident in a care home, in whom the rate ratio (95% CI) associated with dispensing of 12 or more drug classes versus none was 10.8 (8.8, 13.3), and in those without any of the conditions designated as conferring increased risk of COVID-19. Of 17 drug classes postulated at the start of the epidemic to be "medications compromising COVID", all were associated with increased risk of severe COVID-19 and these associations were present in those without any of the designated risk conditions. The fraction of cases in the population attributable to exposure to these drug classes was 38%. The largest effect was for antipsychotic agents: rate ratio 4. 18 (3.42, 5.11). Other drug classes with large effects included proton pump inhibitors (rate ratio 2.20 (1.72, 2.83) for = 2 defined daily doses/day), opioids (3.66 (2.68, 5.01) for = 50 mg morphine equivalent/day) and gabapentinoids. These associations persisted after adjusting for covariates and were stronger with recent than with non-recent exposure. Conclusions: Severe COVID-19 is associated with polypharmacy and with drugs that cause sedation, respiratory depression, or dyskinesia; have anticholinergic effects; or affect the gastrointestinal system. These associations are not easily explained by co-morbidity. Measures to reduce the burden of mortality and morbidity from COVID-19 should (Continued on next page)
Supplementary Information The online version contains supplementary material available at https://doi.org/10.1186/s12916-021-01907-8. Additional file 1: Supplementary information.
Authors' contributions PM, DA, CR, RW, JM, SH and HC provided substantial contributions to the conception or design and drafting of the manuscript. NL, ASP, DG and JM provided substantial contributions to the data acquisition. SK, AW, JB, SM and BG provided substantial contributions to the data analysis or interpretation. All authors contributed to revising the manuscript critically for important intellectual content and approved the final manuscript.
Ethics approval and consent to participate This study was conducted under approvals from the Public Benefit and Privacy Panel for Health and Social Care that allow Public Health Scotland staff to link datasets. Datasets were de-identified before analysis.
Consent for publication Not applicable.
Competing interests HC receives research support and honoraria and is a member of advisory panels or speaker bureaus for Sanofi Aventis, Regeneron, Novartis, Novo-Nordisk and Eli Lilly. HC receives or has recently received non-binding research support from AstraZeneca and Novo-Nordisk. SH received honoraria from Gilead.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
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'relation': { 'has-preprint': [ { 'id-type': 'doi',
'id': '10.1101/2020.07.23.20160747',
'asserted-by': 'object'}]},
'ISSN': ['1741-7015'],
'subject': [],
'container-title-short': 'BMC Med',
'published': {'date-parts': [[2021, 2, 22]]},
'assertion': [ { 'value': '25 August 2020',
'order': 1,
'name': 'received',
'label': 'Received',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '11 January 2021',
'order': 2,
'name': 'accepted',
'label': 'Accepted',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': '22 February 2021',
'order': 3,
'name': 'first_online',
'label': 'First Online',
'group': {'name': 'ArticleHistory', 'label': 'Article History'}},
{ 'value': 'Not applicable.',
'order': 1,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}},
{ 'value': 'HC receives research support and honoraria and is a member of advisory panels '
'or speaker bureaus for Sanofi Aventis, Regeneron, Novartis, Novo-Nordisk and '
'Eli Lilly. HC receives or has recently received non-binding research support '
'from AstraZeneca and Novo-Nordisk. SH received honoraria from Gilead.',
'order': 2,
'name': 'Ethics',
'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}],
'article-number': '51'}