There had been increasing trend in ADs prescribing globally, with almost 2 to 3 folds increase in consumption over the last few years in Asia, Australia, European countries, such as France and the United Kingdom, and the United States [10,11,12,13]. A recent study in the United States showed a 21% increase in the number of ADs, antianxiety, and anti-insomnia prescriptions during the first period of the pandemic between February and March 2020, reaching its peak on 15 March, just after the declaration of COVID-19 as a pandemic by the World Health Organization . This is consistent with our findings; we also found a considerable rise in the prescribing of ADs from February to March 2020. The historic trends in ADs prescribing in England shows an annual increase of ~3 to 4 million prescriptions every year (Table S1). Although this did not change significantly in 2020, our findings suggest that the overall costs associated with ADs in England increased significantly during 2020 compared to 2019, hinting at the potential impact of COVID-19 on the health and mental wellbeing of public in large as also reported elsewhere [15, 16].
Many factors may have contributed to the rise in ADs prescriptions worldwide; the most important factor is the increasing prevalence of depression among the general public which had almost doubled during the COVID-19 pandemic [4, 17]. A study from the United States suggested that the prevalence of depression among adults increased three times during the COVID-19 pandemic compared with the pre-pandemic period . Likewise, the rise in depression symptoms during the COVID-19 pandemic was also reported in the United Kingdom . Similar findings were reported by Pierce et al. in which a deterioration in mental health among the general public in the United Kingdom was found . The increasing number of newly diagnosed cases of depressive disorder, coupled with social isolation, psychological changes, changes in lifestyle associated with COVID-19 pandemic leading to poor quality of life, and temporary suspension of various mental health interventions/services were attributed to the global rise in ADs prescribing, consumption, and associated medication costs.
Various concerns have been raised in the literature about the safety of ADs. Violence, akathisia, and suicidal thoughts are the commonly reported side-effects of ADs, particularly in adolescents and young adults . A review based on the data submitted to the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom showed an increased rate of suicide during early treatment with ADs, particularly SSRIs . Similarly, a meta-analysis of 100,000 patients using ADs concluded that the risk of suicide doubled in children and adolescents, although there was no similar increase in the risk in adults . These findings are particularly important in the context of COVID-19 pandemic as observational data suggest that young adults, i.e., up to 25 years of age, were impacted by the mental health issues during the pandemic, and hence, were more likely to use ADs . It is, therefore, important to optimize the safe use of ADs, particularly in young adults, not only to help with mental health but also in preventing the associated side-effects that may further increase the morbidity and mortality associated with depression in younger adults.
Certain ADs are known for causing weight gain. For instance, all the cyclic ADs block histamine receptors and cause increased appetite . Likewise, treatment with SSRIs for long term, as occurred with major depressive disorder, may result in weight gain. The evidence suggests that that paroxetine and fluvoxamine are the most problematic SSRIs with regard to undesirable weight gain: paroxetine leads to weight gain in 6% of patients , with a gain of weight ranging from 1.6% to 3.6% of baseline body weight [24, 25], while fluvoxamine leads to weight gain of 2.6% of baseline body weight . On the other hand, among the SNRIs, both duloxetine and venlafaxine are associated with weight gain: weight gain ≥7% of baseline weight occurred in 11% of patients receiving duloxetine (either 80 mg/day or 120 mg/day) , whereas the mean weight gain within an average of 18 months with venlafaxine was 7 kg . The weight gain associated with ADs may be undesirable during COVID-19 pandemic since body mass index is a strong independent risk factor for severe course of COVID-19  and obesity itself increases the risk to acquire COVID-19 . Therefore, ADs prescribing of ADs amid COVID-19 should take a personalised approach by considering the patient's body weight.
Limitations of the study
The nationwide data extracted from PCA database provided unique insights into the ADs prescribing trends across England. However, caution should be exercised while extrapolating these findings acknowledging the limitations of the study. First, the findings of the study draw on the number of prescriptions dispensed; therefore, we cannot be assured if the number of items dispensed was all consumed by the patients. Second, we were not able to provide information about the diagnosis or characteristics of individual patients as PCA only provided a population-level data set. Finally, the prescribing and dispensing trends may be characteristic to England and caution should be exercised before extrapolating these findings to other regions.