Eur J Clin Pharmacol (2014) 70:437443

DOI 10.1007/s00228-013-1621-6

PHARMACOEPIDEMIOLOGY AND PRESCRIPTION

Changes in drug prescribing to Italian community-dwelling

elderly people: the EPIFARMElderly Project 20002010
Carlotta Franchi & Mauro Tettamanti & Luca Pasina &
Codjo Djade Djignefa & Ida Fortino & Angela Bortolotti &
Luca Merlino & Alessandro Nobili

Received: 13 August 2013 / Accepted: 26 November 2013 / Published online: 8 January 2014
# Springer-Verlag Berlin Heidelberg 2014

Abstract
Purpose To investigate the changes in the last decade (2000
2010) in drug prescribing among community-dwelling elderly
people aged 6594 years, in relation to age and sex.
Methods We analyzed the data of nearly two million subjects
ranging in age from 65 to 94 years recorded in the Drug
Administrative Database of the Lombardy Region (Italy) from
2000 to 2010. Associations between drug use (at least one
drug, one chronic drug, polypharmacy or chronic
polypharmacy) and age, sex, and year of prescription were
analyzed by logistic regression analysis. We also analyzed
differences in changes linked to sex and age.
Results Between 2000 and 2010, the prescriptions of at least
one drug or one chronic drug increased by 2 % (from 88.0 to
90.3 %; p<0.0001) and 8 % (from 73.8 to 82.0 %; p<0.0001),
respectively, while the mean number of packages/person/year
rose from 34.6 [standard deviation (SD) 32.4] to 48.5 (SD
42.2). During this same period, there was a 10 % increase in
the prevalence of elderly people exposed to polypharmacy (5
different active substances) (from 42.8 to 52.7 %; p<0.0001),
and the prevalence of those exposed to chronic polypharmacy
(5 different chronic drugs) doubled (from 14.9 to 28.5 %; p<
Electronic supplementary material The online version of this article
(doi:10.1007/s00228-013-1621-6) contains supplementary material,
which is available to authorized users.
C. Franchi (*) : L. Pasina : C. D. Djignefa : A. Nobili
Laboratory for Quality Assessment of Geriatric Therapies and
Services, IRCCS-Istituto di Ricerche Farmacologiche Mario
Negri, Via Giuseppe La Masa, 19, 20156 Milan, Italy
e-mail: carlotta.franchi@marionegri.it
M. Tettamanti
Laboratory of Geriatric Neuropsychiatry, IRCCS-Istituto di Ricerche
Farmacologiche Mario Negri, Milan, Italy
I. Fortino : A. Bortolotti : L. Merlino
Regional Health Ministry, Lombardy Region, Milan, Italy

0.0001). Males were less frequently treated than females, except for chronic polypharmacy. People aged 80 years showed
the largest increase in all prescribing patterns. Drug consumption in ATC groups A, H, and N (women) and in B and C (men)
increased most, with the greatest absolute differences occurring
in the consumption of proton pump inhibitors (31.1 %), platelet
aggregation inhibitors (30.1 %), and statins (23.8 %).
Conclusion Prescriptions to community-dwelling elderly
people have increased substantially during the last 10 years.
Although this might indicate an improvement in care, the large
increase in the number of elderly people exposed to
polypharmacy and chronic polypharmacy should be carefully
analyzed in terms of quality of care, patient safety, and costs.
Keywords Drug utilization . Polypharmacy . Trend . Elderly

Introduction
The elderly population is increasing throughout the world. In
Italy, people aged 65 years currently account for 21 % of the
overall population, and it is estimated this proportion will
reach 32 % in 2043. [13] In the last 10 years, the scenario
of drug therapies and guidelines for treating chronic diseases
has changed [46]. The availability of new drugs, increased
use of generics and a more active approach to the treatment of
elderly people [7, 8], supported by new diagnostic tools and
guidelines that suggest lower thresholds for starting drug
[913], have given physicians more opportunityand more
propensityto start or add medications to treatment regimens.
Multimorbidity [1416], high rates of hospitalization [17, 18]
and an increasing number of specialists who treat every single
chronic disease are other factors that may have contributed to
the increase in drug prescription rates.
However, reports on drug prescription changes are scarce
and differ in the presentation of the data and the settings and

438

populations analyzed. A Swedish study in the county of

Holland [19] found that between 1988 and 2002 the total drug
exposure of the countys population nearly doubled. In a
register-based study [20], between 2005 and 2009 the prevalence of polypharmacy (5 drugs) increased by 8 %, and the
prevalence of excessive polypharmacy (10 drugs) increased
by nearly 10 %.
Although data on drug prescribing and expenditure in
different countries have been available as sales statistics for
specific drugs and populations, no study has specifically focused on the elderly. Specifically, the Italian setting and the
trends in recent years have nog yet been explored. In this study
we investigated the changes in the last decade (20002010) in
drug prescribing among community-dwelling elderly people
aged 6594 years in relation to age and sex.

Methods
Data source and study population
This study is a part of a large pharmacoepidemiological
collaborative project on drug prescription for elderly people
living in the Lombardy Region, the EPIFARMElderly Project
(Progetto EPIdemiologia del FARMaco nellAnziano). Data
on drug prescribing were obtained from the Drug Administrative Database of the Lombardy Region, Northern Italy, which
stores all prescriptions covered by the Italian National Health
System (NHS) issued to the nearly ten million individuals
living in the region (around 16 % of the Italian population).
The structure of this database, routinely updated for administrative and reimbursement purposes, has been described in
detail elsewhere [21, 22]. Briefly, each prescription record
contains information on the drug dispensed and the patients
data. Only drugs provided free of charge by the NHS and filled
at the pharmacy are stored. All data used in this study were
managed according to current Italian laws on privacy, and each
person was identified by an anonymous code.
We selected all residents of the Lombardy Region aged 65
94 years between 1 January 2000 and 31 December 2010.
Individuals who died, were institutionalized or were aged 95
years in the index year were excluded. People aged 95 years
were excluded due to problems in tracing drugs dispensed by
nursing homes. However, in a previous study [23], we estimated these individuals accounted for approximately 1 % of
the overall elderly population of the Lombardy Region.
For each year we calculated the prescription prevalence as
the proportion of all subjects who received at least one drug
and as the proportion by age and sex. Chronic drug exposure
was defined as the prescription of at least four packages of a
drug of the same active substance, polypharmacy as the prescription of five or more different active substances, and
chronic polypharmacy as the prescription of five or more

Eur J Clin Pharmacol (2014) 70:437443

different chronic drugs. Co-prescription was defined as the

prescription of a drug belonging to a main ATC group in the
same year in which another drug belonging to a different main
ATC group is prescribed.
All drugs were classified according to the Anatomic Therapeutic Classification (ATC) system. [24] We analyzed ATC
main anatomical groups (the 1st level) and its subgroups (the
2nd and 4th levels) looking for differences between years.
We report data for the first year of observation (2000),
for the last year a complete dataset was available
(2010), and for the year in the middle (2005). Reported
changes are in absolute terms (percentage).
Statistical analysis
We divided age groups into quinquennials, although decennia
were used in the graphs in order not to cause clutter. Reference
groups were females and the 65- to 69-year age group. Differences in drug exposure between 2000 and 2010 were
evaluated by multivariable logistic analyses adjusting for age
and sex (model 1). Interactions between prescription prevalence, sex and age were included in a full model (model 2).
Since about 33 % of people were present in both the first and
last years, a clustered sandwich estimator was used to correct
for non-independence of data. To control for the effects of age
and sex on the differences over time, we reported the results of
the analyses after standardization on the population living
in Lombardy Region in 2005 with very similar results
(differences of <0.5 %).

Results
The general characteristics of community-dwelling elderly
people living in the Lombardy Region in 2000, 2005, and
2010 are reported in Table 1. Women were more prevalent
(around 60 %) and people aged 6574 years old were the
largest group (20002010: 58.953.4 %).
Prescribing patterns from 2000 to 2010, overall,
and in relation to age and sex
The prevalence of elderly people who received at least one
drug prescription rose 2 % from 2000 to 2010, while those
receiving at least one chronic drug increased by nearly 8 %
(Table 1). The prevalence of elderly people with no drug, only
one drug, or two to four drugs fell over time from 12.1 to
9.7 %, from 10.7 to 7.9 %, and from 34.4 % to 29.7 %,
respectively. The increase in prevalence of elderly people
treated with at least one drug was similar for females (from
89.1 to 91.1 %) and males (from 86.2 to 89.4 %), while the
prevalence according to age rose from 86.1 to 87.9 % in those

Eur J Clin Pharmacol (2014) 70:437443

439

Table 1 Main details of elderly people aged 6594 years living in the Lombardy Region in 2000, 2005, and 2010
Variables

Total population of Lombardy Region

Elderly population (6594 years)a
Age (years), mean (SD)
Female
Male
Age groups (years)
6569
7074
7579
8084
8589
9094
No drug
At least one chronic drugb
Polypharmacy (5 drugs)c
Chronic polypharmacy (5 chronic drugs)d
Total prescriptions to the elderly
Total packages to the elderly
Total active substances to the elderly
Number of prescriptions/person/year, mean (SD)
Number of packages/person/year, mean (SD)
Number of active substances/person/year, mean (SD)

2000

2005

2010

9,256,127
1,557,560
75.1 ( 6.9)
941,106
616,454

100
17.0

100
18.3
58.8
41.2

10,155,949
1,930,855
76.1 (6.8)
1,113,400
817,455

100
19.0

60.4
39.6

9,719,718
1,776,297
75.3 (6.9)
1,044,253
732,044

495,296
421,355
325,846
154,535
119,700
40,828
187,764

31.8
27.1
20.9
9.9
7.7
2.6
12.0

557,080
455,344
363,954
250,608
97,249
52,062
197,409

31.4
25.6
20.5
14.1
5.5
2.9
11.1

508,881
521,894
403,308
289,106
161,950
45,716
185,683

26.4
27.0
20.9
15.0
8.4
2.4
9.7

1,148,741

73.8

1,365,099

76.8

1,581,059

82.0

666,125
231,672
21,439,913
47,376,354
979
13.9 (14.8)
34.6 (32.4)
4.6 (4.0)

42.8
14.9

822,930
352,638
31,013,858
61,132,221
1,157
17.6 ( 17.8)
38. 7 ( 35.8)
4.2 ( 5.0)

46.3
19.8

1,018,413
551,170
43,877,720
84,729,502
1,142
22.8 ( 21.8)
48.5 ( 42.2)
4.4 ( 5.6)

52.7
28.5

57.7
42.3

SD, Standard deviation

a

Excluding elderly people living in nursing homes or died

At least four packages of a drug with the same active substance

Five or more different active substances

Five or more different chronic drugs (at least four packages of the same active substance)

aged 6574 years, from 90.7 to 93.4 % in those aged 75

84 years, and from 90.5 to 92.7 % in those aged 8594 years.
The prevalence of elderly people exposed to polypharmacy
increased by 10 % between 2000 and 2010 (from 42.8 to
52.7 %). This was more evident in females (from 44.0 to
53.4 %) and subjects aged 7584 (from 49.0 to 60.8 %) and
8594 (from 51.3 to 63.5 %) years. Finally, the prevalence of
elderly people exposed to chronic polypharmacy doubled in
the period considered (Table 1).

Prescribing patterns from 2000 to 2010 by ATC classification

Electronic Supplementary Material (ESM) Table 1s shows the
changes in drug prescribing to community-dwelling elderly
people from 2000 to 2010 according to the first level of ATC
classification. Although cardiovascular drugs ) were the
most prescribed drug class over time, the prevalence of prescriptions for alimentary tract and metabolism drugs (A),

drugs for blood and blood-forming organs (B), and nervous

system (N) drugs rose markedly from 2000 to 2010.
The main changes in drug prescribing among the first level
of ATC classification involved drugs belonging to classes B
and C for males and A, H, and N for females (ESM Fig. 1s).
No differences were found in relation to age. In 2000 cardiovascular system drugs (C) were co-prescribed mainly
with A, B, M, and N ATC groups. This was confirmed
in 2010, at which time the prevalence of these coprescriptions had increased (A/C: from 29.6 to 41.8 %;
B/C: from 21.0 to 36.2 %; M/C: from 28.1 to 28.6 %;
N/C: from 7.4 to 19.8 %). ESM Table 2s shows the top
ten of the changes at the second level of the ATC
classification. Proton pomp inhibitors (A02BC), platelet
aggregation inhibitors excluding heparin (B01AC), and
statins (C10AA) showed the biggest increases, namely,
31.1, 30.1 and 23.8 %, respectively. Among the nervous
system drugs, selective serotonin reuptake inhibitors
(SSRIs) (N06AB) showed the highest increase (8.7 %).

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Eur J Clin Pharmacol (2014) 70:437443

Table 2 Univariable, multivariable and interaction analyses results

Variables

At least one drug

Univariable analyses
Year
2000
Reference
2010
1.29 (1.281.30)
Multivariable analyses (model 1)
Year
2010
1.24 (1.231.25)
Sex
Female
Reference
Male
0.83 (0.830.84)
Age group (years)
6569
Reference
7074
1.44 (1.431.45)
7579
1.93 (1.921.95)
8084
2.24 (2.212.27)
8589
2.00 (1.972.03)
9094
1.54 (1.511.58)
Interaction between year and sex or age (model 2)
Males
1.07 (1.061.09)
Age 7074 years
1.10 (1.081.11)
Age 7579
Age 8084
Age 8589
Age 9094

years
years
years
years

1.28 (1.251.30)
1.33 (1.301.37)
1.21 (1.171.24)
1.16 (1.111.22)

At least one chronic druga

Polypharmacyb

Chronic polypharmacyc

Reference
1.61 (1.601.62)

Reference
1.49 (1.481.50)

Reference
2.28 (2.272.30)

1.54 (1.531.55)

1.44 (1.431.45)

2.19 (2.182.20)

Reference
0.97(0.960.97)

Reference
0.97 (0.970.98)

Reference
1.33 (1.321.34)

Reference
1.48 (1.471.49)
2.07 (2.052.08)
2.50 (2.472.52)
2.40 (2.372.43)
1.99 (1.962.03)

Reference
1.42 (1.42-1.43)
1.93 (1.921.94)
2.31 (2.292.32)
2.32 (2.302.34)
2.11 (2.092.15)

Reference
1.53 (1.521.54)
2.24 (2.232.26)
2.81 (2.792.84)
2.96 (2.932.99)
2.76 (2.712.80)

1.06 (1.051.07)

1.07 (1.061.08)

1.00 (0.991.01)

1.08 (1.071.10)
1.28 (1.261.30)
1.37 (1.351.40)
1.31 (1.281.34)
1.29 (1.251.34)

1.06 (1.051.07)
1.22 (1.201.23)
1.30 (1.281.32)
1.30 (1.281.32)
1.30 (1.261.34)

1.02 (1.011.04)
1.14 (1.121.16)
1.23 (1.201.25)
1.28 (1.261.31)
1.32 (1.281.36)

OR, Odds ratio; CI, confidence interval

Data are presented as the odds ratio with the 95 % confidence interval given in parenthesis
Model 1: Logistic regression analysis adjusted for age and sex. Model 2: Model 1 plus interaction between year and sex or age
a

At least four packages of a drug with the same active substance

Five or more different active substances

Five or more different chronic drugs (at least four packages of the same active substances)

Univariable, multivariable, and interaction analyses

Table 2 summarizes the univariable, multivariable and interaction analyses. In comparison to 2000, community-dwelling
elderly people living in the Lombardy Region in 2010 had a
significantly higher risk of being treated with at least one drug.
This risk was even greater in the case of chronic treatment.
Males were in general less treated than females (one drug, one
chronic drug or polypharmacy) but, as shown by the interactions analysis, their drug consumption increased more than for
females. Conversely, males had more frequently chronic
polypharmacy in 2000 and 2010 (OR 1.33; 95%CI 1.321.34).
Prescription prevalence reached its maximum in patients
aged 8084 years with the prescribing pattern of one drug or
one chronic drug and in those aged 8589 years with the
prescribing pattern of chronic polypharmacy. Individuals in
the age class 8084 years showed the maximum increase in
prescription prevalence for at least one drug/one chronic drug,

and those in the older age classes (8084 years) showed the
maximum increase in prescription prevalence for
polypharmacy. Finally, in chronic polypharmacy, the increase
continued to rise with advancing age.

Discussion
To our knowledge only a few studies have recently investigated the changes in prescribing trends in the elderly during
this last decade. The results of our study indicate that the
prevalence of drug prescriptions issued to communitydwelling elderly people aged 6594 years increased from
2000 to 2010 for both overall use of drugs (at least one drug)
and chronic treatments (at least 4 packages of the same active
substance) and polypharmacy (5 different active substances),
independently of the age structure of the elderly population.
Although males were always less exposed than females to

Eur J Clin Pharmacol (2014) 70:437443

drugs (except for chronic polypharmacy), the changes between 2000 and 2010 in prescribing prevalence in the male
subjects were larger than those in the female subjects. A Swedish
study that compared the patterns of drug use during a 15-year
period (19882002) for all ages (from 0 to 80 years) found that
drug exposure for the entire study population doubled during the
study period [19] and that the number of prescriptions for those
aged 60 years increased by 133 %. Another study found that
both the crude number of prescription claims and prescription
rates in adults aged 65 years increased dramatically over a
period of 10 years (19972006) in Ontario, with the greatest
changes occurring in females aged 85 years [25].
To study whether there was an association between age class
and increased drug exposure, we used a multivariable analysis
and found an age-related increasing risk to receive drugs that was
particularly evident for chronic drugs and chronic polypharmacy.
In patients exposed to at least one drug or to at least one chronic
drug the maximum increase was seen in the age group of 8084
years. In a previous study on prescription data for the 2005, we
found that age was the most important predictor of exposure to
chronic therapies and polypharmacy [18]. In the present study, in
which we standardized the prevalence of the elderly population
according to the population residing in the Lombardy Region in
2005, the results obtained were almost identical, indicating that
the observed changes in the prevalence of drug exposure between 2000 and 2010 cannot be explained by a change in the age
structure of the population. A possible explanation of the increase
in the number of drug prescriptions might be the increase in the
prevalence of diagnoses of chronic diseases and multimorbidity
in these individuals, which could have induced physicians to
prescribe more drugs according to the specific guidelines for
each single chronic disease. Another explanation of the increases
in drug prescribing across our 10-year study period might be the
implementation of new guidelines for the treatment of many
chronic diseases (e.g., diabetes, hypertension, osteoporosis) that
lowered the thresholds for starting drug treatments. This latter
phenomenon is evidenced by the increase in prescriptions for the
drug classes of the cardiovascular system (C), blood and bloodforming organs (B), alimentary tract and metabolism (A) and
central nervous system (N). The small reduction in prescribing
for musculoskeletal drugs (M) might be related to safety issues
(particularly the increased risk of cardiovascular events, gastrointestinal bleedings, and impaired renal function) for coxibs and
other non steroidal anti-inflammatory drugs. The largest increases in prescribing drugs in the therapeutic subgroups between
2000 and 2010 were for the lipid-modifying agents (C10),
followed by antithrombotic agents (B01), and agents acting on
the reninangiotensin system (C09). Silwer et al. [19] reported
the largest changes in B01, from approximately zero to 43
prescriptions per 100 inhabitants, while C09 prescriptions increased tenfold, calcium channel blockers (C08) prescriptions
tripled, and C10 prescriptions increased from approximately zero
to 14 defined daily dose per 100 inhabitants. In another study,

441

Bajcar et al. [25] found that all classes of medication showed an

increase in average annual claims per person, with the top ten
being medications for osteoporosis (+1.965 %), lipid-lowering (+
572 %), thyroid replacements (+200 %), psychotropics (+
198 %), cardiovascular (+191 %), diabetes (+188 %), gastrointestinal (+155 %), narcotics/analgesics (+78 %), and corticosteroids (+44 %).
In our study analgesics (particularly opioidsdata not shown)
and psychoanaleptics (particularly antidepressantsdata not
shown) showed the highest increase, occupying the sixth and
seven positions, respectively, among the top ten therapeutic
subgroups (3rd ATC level). These changes might be related to
changes in the Italian NHS reimbursement policy. One study
showed an increased prevalence in antidepressant (AD) use from
2000 to 2007, especially for SSRIs [26], that could be explained
by the fact that the Italian NHS started to fully reimburse SSRIs
from 2001 but also by the persistence of the treatment and the
broader indications for antidepressants [26].
Despite these increases in many different drug therapies, there
are still only few clinical trials routinely enrolling elderly patients,
specifically those aged 75 years. Moreover, clinical guidelines
based on the same trials contribute to the problem by focusing on
the benefits of individual medications on specific diseases, without considering the risks and the frequent lack of compliance
with treatments for multiple coexisting conditions [27].
Doctors are now faced with the contradiction of being able
to treat patients with new therapeutic agents on the market
while at the same time having to assess and control an increasing number of potential harmful drugdrug interactions,
adverse drug reactions, and inappropriate use of medications,
all factors with important implications for quality of care,
safety, and cost [28].
We also found that although community-dwelling elderly
people living in the Lombardy Region showed an increase in
the number of prescription claims and packages per person,
the number of active substances per person per year remained
stable over time. This could be partly explained by new
formulations of some drugs during the study, but more probably by a change in chronic treatment since chronic prescription prevalence increased by 8 % compared to 2 % for nonchronic treatment. The 10 % increase in the prevalence of
polypharmacy between 2000 and 2010 and the doubling of
the prevalence of chronic polypharmacy supports this hypothesis. Further analyses will help clarify the reason for this
change in chronic treatment over the years.
Limitations
Although we analyzed a large regional dataset that included
data on nearly two million people aged 65 years, this study
has some limitations. First, our findings may not be fully
representative of other regions. However, data from the National Drug Monitoring Center of the Italian Drug Agency

442

shows that the prescribing profile for the elderly in the Lombardy Region is comparable to that at the national level.
Second, common to many studies based on administrative
prescription databases, there is a lack of information on the
diseases and the indication for which the drugs are prescribed.
However, drug prescribing has been used in many studies as a
proxy for identifying comorbidity and disease-specific risk
factors, as well as for evaluating the burden of diseases in
the elderly population [29, 30]. Third, there is a lack of data on
drugs not reimbursed by the NHS and over-the-counter medications (not including drugs commonly used, such as benzodiazepines, peripheral vasodilators, vitamins, laxatives, and
seasonal drugs). This could result in an under-estimation of
polypharmacy and of changes in drug use. Fourth, information on effective drug intake is absent. However, at least for
chronic drugs, the periodic prescription may serve as an
indirect indicator of regular drug intake. Finally, some changes in drug prescribing during the study period might have been
influenced by regulatory decisions on safety and efficacy
implemented by the Italian Drug Agency, such as those relative to coxibs, non-steroidal anti-inflammatory drugs, and
antipsychotics, to mention only the most common.

Conclusions
The results of this study show that exposure to drug therapies
(overall use, chronic, and polypharmacy) of communitydwelling elderly people living in the Lombardy Region
(Italy) rose significantly from 2000 to 2010. These changes
might have been influenced by the presence of new drugs and
by increases in the diagnosis of chronic disease and
multimorbidity which could have induced physicians to prescribe more drugs, following new specific guidelines and
lower cutoffs for starting treatment. These developments were
particularly evident for exposure to chronic drugs and chronic
polypharmacy and for patients aged 75 years.
These new trends have important implications in terms of
monitoring costs and the appropriateness of drug prescribing
in these patients, and on the need to educate physicians and
create interdisciplinary teams involving pharmacists, nurses,
and social workers, for periodic critical reassessment of drug
profiles of elderly patients exposed to polypharmacy

Competing interests None.

Funding This study was supported by grants from the Region Health
Ministry of the Lombardy Region (Progetto EPIdemiologia dei FARMaci EPIFARM).
Ethics approval All data were managed according to the current Italian
law on privacy.

Eur J Clin Pharmacol (2014) 70:437443

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