How Chronic Is Polypharmacy in Old Age?

A Longitudinal Nationwide Cohort Study

Jonas W. Wastesson, PhD; Lucas Morin, MSc; Marie-Laure Laroche, PhD; Kristina Johnell, PhD

Disclosures

J Am Geriatr Soc. 2019;67(3):455-462. 

In This Article

Discussion

This large longitudinal cohort study tracking monthly changes in drug utilization among older adults in Sweden shows that polypharmacy (concurrent use of five or more drugs) is often a chronic state. This was demonstrated with two complementary approaches.

First, when focusing on the duration of polypharmacy episodes, our data clearly show that polypharmacy is persistent for a majority of older adults. About 75% of the individuals with polypharmacy at baseline remained exposed to polypharmacy for at least 12 consecutive months. Moreover, even though persons with a new polypharmacy episode at baseline were more likely to discontinue polypharmacy in the short term, more than three quarters of the people who stopped polypharmacy eventually transitioned back to polypharmacy before the end of the study period. This suggests that polypharmacy is often a chronic state; however, a substantial share of older adults experience short episodes of polypharmacy and are thus exposed to its potential harms in a transient rather than persistent manner. This is especially true among those who are prescribed three to four medications for the management of chronic diseases (and who are likely to fluctuate around the threshold of five drugs used to define polypharmacy).

Another way to assess the longitudinal exposure to polypharmacy is to investigate the proportion of months that older adults spend with polypharmacy. Contrary to duration, which measures the length of continuous and uninterrupted polypharmacy episodes and is therefore particularly sensitive to grace periods and right censoring (eg, survival), the fraction of time with polypharmacy describes the burden of polypharmacy with respect to the available follow-up time. This approach is comparable to the method proposed by Franchi et al, for defining chronic polypharmacy users, which consists in measuring the proportion of individuals exposed to polypharmacy at least 6 of 12 months.[32] In the present study, we found that 80% of older adults had a high fraction of time with polypharmacy (ie, spent 80% or more of follow-up with polypharmacy), which is indicative of a chronic exposure. Risk factors associated with high fraction of time with polypharmacy included higher age, female sex, living in an institution, chronic multimorbidity, and multidose dispensing.[33–35] When using the same cutoff value as Franchi et al[32] (namely, being exposed to polypharmacy during more than 50% of the available months), 42% of older adults who started a new polypharmacy episode at baseline had chronic polypharmacy in our study. An unexpected finding was that the adjusted probability of spending a large proportion of months with polypharmacy was higher among people residing in the community than in nursing homes. However, more detailed analyses revealed that this association was mostly driven by multidose dispensing: the small share of persons living in the community with multidose drug dispensing had the largest fraction of time with polypharmacy. The finding that people with multidose dispensing spend a higher fraction of time with polypharmacy is in agreement with previous Swedish studies showing that persons with multidose dispensing have fewer changes made to their drug regimens (eg, dose adjustments, drug discontinuations, and newly prescribed drugs).[30,36] One suggested reason for the fewer changes is that prescribers have the possibility to renew all drugs at once, which is not possible with ordinary prescriptions.[36]

There currently exists no consensual definition of polypharmacy, but two aspects have been widely discussed: the number of drugs that define polypharmacy in a clinically meaningful way[37,38] and the criteria that would allow for drawing the line between appropriate and inappropriate polypharmacy.[20] These two dimensions, the intensity and the composition of polypharmacy, are important. However, only few studies have made a distinction between chronic and transient polypharmacy.[19] Our study shows that exposure to polypharmacy is not always stable over time and that transient polypharmacy episodes are not uncommon. The notion of temporality should thus be better accounted for in the future. Observational studies that have investigated the association between polypharmacy and negative health outcomes have seldom considered polypharmacy as a time-varying exposure.[2,39] Yet, doing so would considerably improve the assessment of harms of polypharmacy and could potentially elucidate the question of whether the effect of polypharmacy is cumulative (ie, longer exposure to polypharmacy leads to an accumulated risk of adverse effects) or if polypharmacy is hazardous even if exposure is short lasting. The potential cumulative hazard of polypharmacy was recently highlighted in a British study, which demonstrated that the associations between polypharmacy and physical and cognitive capabilities were more pronounced among older adults with a long-term exposure to polypharmacy.[23]

Strengths and Limitations

The main strength of this study is that it includes the entire population of older adults aged 65 years or older with polypharmacy in Sweden, followed up for 3 years. The monthly assessments of polypharmacy exposure provide better time resolution of the fluctuations in polypharmacy status than earlier survey-based studies with longer time periods between survey waves.[12–16,23] There are some notable limitations to the study. First, we assessed monthly exposure to polypharmacy rather than weekly or even daily exposure periods, which could overlook some of the fluctuations in drug use. The choice of monthly time windows was dictated by the considerable computation power required to calculate concurrent drug exposure for a population of 700,000 individuals over 3 years with a more detailed time resolution. Drugs used in hospitals are not recorded in the Swedish Prescribed Drug Register, and a 1-month stay in the hospital could thus result in a change in polypharmacy because of not filling new prescriptions. Additionally, over-the-counter drugs are not recorded in the Swedish Prescribed Drug Register; this most likely leads to an underestimation of the individual burden of polypharmacy. Adherence to different medications could lead to misclassification of the exposure to polypharmacy in this study: our data do not provide information about drugs that were prescribed but never dispensed or whether the dispensed drugs were actually consumed. Our results should be interpreted in the light of this limitation. To reduce the risk of overestimating short-term fluctuations, we only considered polypharmacy to be discontinued if 2 consecutive months were spent without polypharmacy. Second, we calculated the number of drugs by summing together all distinct ATC codes, including medications intended for short-term use that do not contribute to chronic polypharmacy. However, considering all prescribed drugs reflects the natural course of polypharmacy in the older population. Third, we tried to isolate people with a new episode of polypharmacy at baseline from those who had already been exposed. This is because incident polypharmacy users have been proposed as a promising target for future interventions.[23] However, because we could only construct a 6-month washout period before baseline, we cannot be certain that these individuals have a truly incident episode of polypharmacy. Last, polypharmacy is often a result of multimorbidity. We were able to account for the number of chronic conditions at baseline. However, future studies should also investigate how severity of different conditions affects chronicity of polypharmacy.

In conclusion, in this longitudinal study of more than half a million older people followed up for up to 3 years, we found that that about 75% of the persons with polypharmacy were exposed to polypharmacy for at least 12 consecutive months. A large majority of older adults was also exposed to polypharmacy for more than 80% of the total study months. Our results therefore suggest that polypharmacy is most often chronic, but that a substantial share of older adults experience short, recurring episodes of polypharmacy and are thus exposed to its potential harms in a transient rather than persistent manner. This highlights the need to consider polypharmacy as a dynamic state in both epidemiological studies and in clinical practice.

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