Discussion
Primary care prescribing has profoundly changed during the COVID-19 pandemic. Increased prescribing and dispensing of medications used in chronic obstructive pulmonary disease (COPD), insulin-dependent diabetes, and transplant immunosuppression was observed, while drugs involving face-to-face visits were avoided. Elderly care medications, including anti-dementia drugs and those used in the treatment of Parkinson’s disease, experienced an alteration of their upwards trend towards a decline during the pandemic. Somewhat surprisingly, the majority of drugs associated with chronic health conditions such as hypertension, type 2 diabetes and mental health conditions, were not grossly affected.
Our results indicate increased prescribing and dispensing of health-critical drugs during the initial pandemic months. Affected medications include insulins, transplant immunosuppressants and respiratory drugs such as inhalers (figure 1). Since prescriptions of these medications increased during March and April 2020, returning to normal thereafter, we surmise that that the observed stockpiling of consumer goods translated into medication stockpiling.15 We theorise that patients anticipated shortages of medications and reduced ability to attend GP practices, and so were motivated to request prescription of extra medications, or seek dispensing of already prescribed items. A survey of solid organ transplant recipients in Germany highlighted this group’s particular fears regarding COVID-19.28 Montelukast deviated minimally from prediction, as did the beclometasone/formoterol fumarate combination inhaler, suggesting that these trends may be driven by patients with COPD, rather than asthma. The observed increased prescribing and dispensing of prednisolone and doxycycline, commonly used in COPD rescue packs (a ‘pack’ containing a combination of steroid and antibiotic kept by the patient and used in the event of a COPD exacerbation), supports this hypothesis. Indeed, patients with COPD are particularly at risk of mental health disorders in response to lockdown.29 The possible difference between patients with COPD and asthma is interesting, as UK shielding guidelines were similar for both patients with severe COPD and severe asthma.30 Prescribing of oral diabetic medications did not significantly differ from forecast, suggesting that medications for individuals with type 1 diabetes, for whom abstinence from insulin would be most detrimental, are responsible for the spike in insulin and testing prescriptions. Insulins were reportedly stockpiled in response to the proposed UK exit from the EU in 2019,31 although we find no evidence of increased prescribing and dispensing of insulin during that time. Prescribing and dispensing of both glucose and glucagon increased in March 2020, and their observed annual summer prescribing peak is consistent with previous reports.32 33 Possible alternative explanations for increased prescribing and dispensing during the lockdown period include increased GP prescribing, or increased dispensing by patients’ pharmacies when attempting to fulfil prescriptions, although to our knowledge there is not yet any peer-reviewed evidence to support this theory.
The alarming spike in palliative care medication prescription coincided with the UK peak overall deaths. National Institute for Health and Care Excellence (NICE) guidelines for management of COVID-19 at the end of life specifically recommends levomepromazine for control of delirium or agitation,34 which has been borne out in observed community prescribing (figure 2). A recent survey of practitioners regarding provision of end-of-life care highlights the unprecedented demand on the service.35 Further to the high death toll among the elderly, their overall care appears to have suffered throughout 2020, with several drugs used in the management of dementia and Parkinson’s disease exhibiting a reduction in absolute number of prescriptions dispensed in 2020, rather than the steady increase they had been experiencing prior to this. This correlates with the observed lack of new diagnoses of dementia,36 37 with the attrition possibly reflecting patient deaths, as treatment with drugs to combat Parkinson’s disease and dementia is often lifelong. It may also be possible, however, that elderly patients were unable to visit pharmacies to have their prescriptions dispensed due to reduced social support from relatives during lockdown, shielding advice or fears of leaving the house.
Prescribing of drugs involving face-to-face visits reduced during the pandemic, including intramuscular injections, contraceptive implants, practice-based diagnostic tests, and local anaesthetic agents. This is in line with the observed dramatic decrease in face-to-face consultations recorded during 2020.6 The depot antipsychotic medications were an exception, likely due to their enforced administration under the mental health act. Despite guidance advising switching patients from warfarin to direct oral anticoagulants (DOACs) in order to minimise clinic visits,38 and a preprint study reporting that 12.2% of patients taking warfarin in England were switched (most commonly to edoxaban or apixaban) between March and May 2020,39 we detected no significant deviation from prediction in prescribing of warfarin or DOACs during 2020. The aforementioned study includes only 40% of England’s population, and does not appear to include dispensing data, possibly accounting for these discrepancies.
Despite the considerable attention hydroxychloroquine received as a potential COVID-19 therapy, other antirheumatic drugs exhibited a similar degree of increased prescribing. One explanation of the observed increase is its use in chronic health conditions rather than to perceived benefits against COVID-19, although perhaps reduced availability of hydroxychloroquine due to diversion for COVID-19 therapy resulted in increased switching to alternatives. Indeed, prescribing of dexamethasone fell during COVID-19 despite widespread publicity of its benefit,40 possibly as a result of fewer new cancer diagnoses, or possibly due to supply issues in primary care with increase hospital demand for the drug.
A reduction in transmissible childhood diseases (including measles, mumps, rubella, scarlet fever and whooping cough) has been reported during 2020.41 Similarly, we observed a reduction in prescribing of antibiotics commonly used to treat common bacterial illnesses in children, including phenoxymethylpenicillin; we surmise that this is due to reduced overall social contact among children, including national lockdown, as well as shop and school closures, although this is an area in which much further work is needed to ascertain whether transmission was indeed reduced, or healthcare-seeking behaviour was curbed. While there are concerns that telephone consultation is leading to a generalised overuse of antibiotics in primary care, this is not apparent among our results.42 Due to widespread travel restrictions, prescribing of travel-related vaccines and medications fell dramatically. Norethisterone has a summer-predominant seasonality, thought to reflect attempts to avoid periods during travel,43 which was lost during 2020.
Prescribing of orlistat exhibits an almost 25% increase in prescribing in summer compared with winter, although this peak was almost completely lost during 2020. To our knowledge, this seasonality has not been described previously, and does not appear to coincide with peak dieting motivation,44 45 calorie intake or seasonal exercise.46 Colchicine also displayed seasonality, in agreement with preprint data regarding the summer-predominance of gout.47 There was a slight peak in nicotine prescribing during January, in agreement with published data.48
No antidepressant deviated significantly from forecast at any point in 2020. This likely multifactorial, and is is at odds with our prespecified hypothesis. Indeed there has been a reported reluctance for patients to attend primary care for mental health concerns,49 while a clear increase in symptoms of depression has been described,18 and intentional drug overdoses have spiked during COVID-19,50 51 betraying a further deterioration in general mental health. While there is some suggestion that patients are increasingly avoiding antidepressant medications due to publicised withdrawal effects,52 patients experiencing low mood as a result of lockdown may be facing delayed diagnosis, and likely represent an underserved group during the pandemic, thus reducing access to comprehensive investigation of physical causes of low mood, and to first-line treatments such as cognitive behavioural therapy.
Our results reveal the effects of several recent medication approvals and withdrawals. Prescribing of ranitidine dropped by 99.6% in August 2020, following its suspension in mid-2019 due to a carcinogenic ingredient.53 This was offset by an increase in famotidine and cimetidine. Prescriptions of ingenol mebutate fell 99.6% by August 2020 due to its suspension by the European Medicines Agency in the previous February.54 Prescription of the subcutaneous glucagon-like peptide-1 agonists fell gradually during 2020, possibly due to the recent approval of oral semaglutide.55
What this study adds
Our analysis provides some of the first published quantifiable impact of COVID-19 on primary care prescribing, and further adds to existing evidence regarding the impact of the pandemic on both acute and chronic health conditions. We observe trends in increased prescribing and dispensing of multiple medications relating to health-critical conditions, and present mediation stockpiling as possible explanation of these results, with others including altered GP prescribing or pharmacy dispensing habits. This research reveals issues surrounding reliance on in-person healthcare visits, which may discourage compliance or invoke fear among patients, thus highlighting societal groups who may experience disproportionate detriments in care during lockdown. Overall, however, measures taken by primary care practitioners to maintain prescription of medications for long-term health conditions, such as increased electronic repeat prescribing,56 57 appear to have been successful.
Strengths and limitations
We analysed an extensive dataset including dispensed prescriptions from the whole of England over the 6 years prior to the COVID-19 pandemic. Our forecast overlapped with several months of prepandemic data, thus validating the model. However, due to the volume of data analysed, we were unable to offer comparison of alternative forecast models. One major limitation of our study is that it does not fully elucidate patient attitudes to their health conditions; only information regarding dispensed prescriptions is captured, and not patient compliance with prescribed medications. In addition, we do not have data regarding absolute disease incidence, thus it is not clear from our data whether changes in number of prescriptions represents changing incidence of certain conditions during the pandemic, or simply a reluctance to interact with healthcare professionals for diagnosis. Due to the limitations of the dataset, we were unable to draw conclusions regarding differential prescribing by patient group during the pandemic, although were able to make some limited inferences based on the class of drug prescribed, for example, those drugs commonly used in paediatric populations or in elderly care.