Background and purposePolypharmacy is becoming increasingly common owing to the ageing population, which can pose problems for patients and society. We investigated the trends in polypharmacy and underlying drug groups among adults in the Netherlands from 1999 to 2014 stratified by age, and compared these with findings from the United States (US).MethodsWe conducted a repeated cross-sectional study using the Dutch IADB.nl prescription database. All patients aged 20 years and older in the period 1999 to 2014 were included. Polypharmacy was defined as the dispensing of five or more chronic drugs at the pharmacological subgroup level. Chi-square tests were applied to calculate the p-value for trends. Changes in prevalences were compared between the Netherlands and the US.ResultsThe prevalence of polypharmacy increased from 3.1% to 8.0% (p-value for trend <0.001) over 15 years, and increased in all age groups. The highest rates were observed in patients aged ≥65 years, but the relative increase over time was higher in the younger age groups. Overall, large increases were observed for angiotensin-II inhibitors, statins and proton-pump inhibitors. The relative increase in polypharmacy was larger in the Netherlands than in the US (ratio of polypharmacy prevalence 2.4 versus 1.8). The Netherlands showed larger relative increases for angiotensin-II inhibitors, statins, proton-pump inhibitors, biguanides and smaller relative increases for antidepressants, benzodiazepines and insulins.ConclusionsPolypharmacy more than doubled from 1999 to 2014, and this increase was not limited to the elderly. The relative increase was larger in the Netherlands compared to the US, which was partly due to larger increases in several guideline-recommended preventive drugs.

Aims Polypharmacy is common in people with diabetes and is associated with the use of potentially inappropriate medication (PIM). This study aimed to assess trends in the prevalence of polypharmacy and PIM in older and middle‐aged people with diabetes. Methods A repeated cross‐sectional study using the University Groningen IADB.nl prescription database was conducted. All people aged 45 years and over who were treated for diabetes registered in the period 2012–2016 were included. Polypharmacy was assessed for three age groups. PIMs were assessed using Beers criteria for people ≥65 years old, and PRescribing Optimally in Middle‐aged People's Treatments (PROMPT) criteria for 45–64 years old. Chi‐square tests and regression analysis were applied. Results The prevalence of polypharmacy increased significantly in all age groups in the study period. In 2016, the prevalence of polypharmacy was 36.9% in patients aged 45–54 years, 50.3% in those aged 55–64 years, and 66.2% in those aged ≥65 years. The prevalence of older people with at least one PIM decreased by 3.1%, while in the middle‐aged group this prevalence increased by 0.9% from 2012 to 2016. The most common PIMs in both age groups were the use of long‐term high‐dose proton pump inhibitors, benzodiazepines and strong opioids without laxatives. Of those, only benzodiazepines showed a decreasing trend. Conclusions Polypharmacy increased in older and middle‐aged people with diabetes. While the prevalence of PIM decreased over time in older age, this trend was not observed in middle‐aged people with diabetes. Efforts are needed to decrease the use of PIMs in populations already burdened with many drugs, notably at middle age.

BackgroundA number of transporter proteins are expressed in the placenta, and they facilitate the placental transfer of drugs. The inhibition of P-glycoprotein (P-gp) was previously found to be associated with an increase in the risk of congenital anomalies caused by drug substrates of this transporter. We now explore the role of other placental transporter proteins.MethodsA population-based case-referent study was performed using cases with congenital anomalies (N = 5,131) from EUROCAT Northern Netherlands, a registry of congenital anomalies. The referent population (N = 31,055) was selected from the pregnancy IADB.nl, a pharmacy prescription database.ResultsTen placental transporters known to have comparable expression levels in the placenta to that of P-gp, were selected in this study. In total, 147 drugs were identified to be substrates, inhibitors or inducers, of these transporters. Fifty-eight of these drugs were used by at least one mother in our cases or referent population, and 28 were used in both. The highest user rate was observed for the substrates of multidrug resistance-associated protein 1, mainly folic acid (6% of cases, 8% of referents), and breast cancer resistance protein, mainly nitrofurantoin (2.3% of cases, 2.9% of referents). In contrast to P-gp, drug interactions involving substrates of these transporters did not have a significant effect on the risk of congenital anomalies.ConclusionsSome of the drugs which are substrates or inhibitors of placental transporters were commonly used during pregnancy. No significant effect of transporter inhibition was found on fetal drug exposure, possibly due to a limited number of exposures.