Relation of severe COVID-19 to polypharmacy and prescribing of psychotropic drugs: the REACT-SCOT case-control study

Abstract

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 https://EUPAS35558

SciScore for 10.1101/2020.07.23.20160747: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Institutional Review Board Statement	not detected.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.
Sex as a biological variable	not detected.

Table 2: Resources

No key resources detected.

Results from OddPub: Thank you for sharing your code.

Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

A limitation of this study is that we do not have morbidity data from primary care, which would include risk factors such as smoking and coding of presenting complaints. Another limitation is that it is not possible to capture hospital prescribing data which includes biologic agents that have immunosuppressive effects. Strengths of this study are that diagnoses are based on hospital discharge records coded to ICD-10 (rather than the SNOMED-CT codes used in primary care databases), and that drug exposure is based on dispensed rather than issued prescriptions. The mechanisms postulated by Laporte and Healy for drugs to increase risk of severe COVID-19 include sedation, respiratory depression, respiratory dyskinesia and anticholinergic effects4. We note that as SARS-CoV-2 is at least partly an enteric infection12 and the ACE2 receptor is expressed in the intestine, it is plausible that proton pump inhibitors and other drugs acting on the gastrointestinal tract could increase susceptibility to severe infection. It may be relevant to investigate these associations in other countries where COVID-19 epidemics have been especially severe and overprescribing of drug classes such as proton pump inhibitors13–15 or opioids16 has been reported previously. We emphasize that because of the relationship of COVID-19 to polypharmacy, associations with specific drug classes cannot be studied without taking into account how those drug classes are related to the profile of drug prescribing. Of th...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

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