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, Public Health Scotland COVID-19 Health Protection Study Group

*Corresponding author for this work

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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 include reinforcing existing guidance on reducing overprescribing of these drug classes and limiting inappropriate polypharmacy. Registration: ENCEPP number EUPAS35558
Original languageEnglish
Article number51 (2021)
Pages (from-to)1-11
Number of pages11
JournalBMC Medicine
Publication statusPublished - 22 Feb 2021


  • aged
  • aged, 80 and over
  • COVID-19/chemically induced
  • case-control studies
  • comorbidity
  • critical care/trends
  • dose-response relationship, Drug
  • drug prescriptions
  • female
  • humans
  • male
  • middle aged
  • polypharmacy
  • psychotropic drugs/adverse effects
  • Scotland/epidemiology
  • severity of Illness Index
  • antipsychotic agents
  • COVID-19
  • pharmacoepidemiology
  • gabapentinoids
  • opioids
  • overprescribing
  • proton pump inhibitors

ASJC Scopus subject areas

  • General Medicine


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