Trends in Prescription Drug Use Among Adults in the United States ...
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Trends in Prescription Drug Use Among Adultsin the United States From 1999-2012Elizabeth D. Kantor, PhD, MPH; Colin D. Rehm, PhD, MPH; Jennifer S. Haas, MD, MSc;Andrew T. Chan, MD, MPH; Edward L. Giovannucci, MD, ScD
IMPORTANCE It is important to document patterns of prescription drug use to inform bothclinical practice and research.
OBJECTIVE To evaluate trends in prescription drug use among adults livingin the United States.
DESIGN, SETTING, AND PARTICIPANTS Temporal trends in prescription drug use wereevaluated using nationally representative data from the National Health and NutritionExamination Survey (NHANES). Participants included 37 959 noninstitutionalized US adults,aged 20 years and older. Seven NHANES cycles were included (1999-2000 to 2011-2012),and the sample size per cycle ranged from 4861 to 6212.
EXPOSURES Calendar year, as represented by continuous NHANES cycle.
MAIN OUTCOMES AND MEASURES Within each NHANES cycle, use of prescription drugs in theprior 30 days was assessed overall and by drug class. Temporal trends across cycles wereevaluated. Analyses were weighted to represent the US adult population.
RESULTS Results indicate an increase in overall use of prescription drugs among US adultsbetween 1999-2000 and 2011-2012 with an estimated 51% of US adults reporting use of anyprescription drugs in 1999-2000 and an estimated 59% reporting use of any prescriptiondrugs in 2011-2012 (difference, 8% [95% CI, 3.8%-12%]; P for trend <.001). The prevalence ofpolypharmacy (use of �5 prescription drugs) increased from an estimated 8.2% in1999-2000 to 15% in 2011-2012 (difference, 6.6% [95% CI, 4.4%-8.2%]; P for trend <.001).These trends remained statistically significant with age adjustment. Among the 18 drugclasses used by more than 2.5% of the population at any point over the study period, theprevalence of use increased in 11 drug classes including antihyperlipidemic agents,antidepressants, prescription proton-pump inhibitors, and muscle relaxants.
CONCLUSIONS AND RELEVANCE In this nationally representative survey, significant increasesin overall prescription drug use and polypharmacy were observed. These increases persistedafter accounting for changes in the age distribution of the population. The prevalence ofprescription drug use increased in the majority of, but not all, drug classes.
JAMA. 2015;314(17):1818-1831. doi:10.1001/jama.2015.13766
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Author Affiliations: Authoraffiliations are listed at the end of thisarticle.
Corresponding Author: Elizabeth D.Kantor, PhD, MPH, Department ofEpidemiology and Biostatistics,Memorial Sloan Kettering CancerCenter, 485 Lexington Ave,Second Floor, New York, NY 10017([email protected]).
Research
Original Investigation
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U se of prescription drugs represents a major expendi-ture in the United States,1 and research suggests thatuse of prescription drugs is increasing.2 Yet much of
the information about prescription use is derived from phar-macy databases or expenditure data,1,3,4 neither of which di-rectly captures use at the population level. Although severalstudies have sought to assess prescription drug use on thepopulation level,5-15 these studies are either outdated, nar-row in scope, or limited to certain populations such as olderindividuals or those with a given clinical indication.
An updated comprehensive assessment of prescriptiondrug use is important given that practice patterns are continu-ally evolving to reflect the changing health needs of the popu-lation, advances in treatment, new clinical guidelines, the en-trance or exit of drugs from the market, and shifts in policiesregarding drug marketing and promotion. Because of this dy-namic climate, it is important to document patterns of pre-scription drug use to inform both clinical practice and re-search, while also identifying population subgroups with thepotential for underuse, misuse, and polypharmacy.
Nationally representative data from the National Healthand Nutrition Examination Survey (NHANES) were used to es-timate the prevalence of prescription drug use from 1999-2000 to 2011-2012.
MethodsData Source and Study PopulationNHANES is a nationally representative cross-sectional surveyof civilian noninstitutionalized persons living in the UnitedStates.16 Analyses for our study are based on data collected frompersons aged 20 years and older during the 7 most recent cycles.The selection of cycles was determined by data availability:1999-2000 represents the first year of continuous NHANES,and 2011-2012 is the most recent cycle for which data are avail-able. As a stratified, complex, multistage, probability-based sur-vey, NHANES oversamples older adults, low-income individu-als, and certain racial/ethnic groups; participants were assignedweights to account for their unequal sampling probability andnonresponse.
All participants provided written informed consent, anddata are publicly available.17 This study was deemed exemptfrom human subjects approval by the Harvard T. H. ChanSchool of Public Health institutional review board.
Assessment of Prescription Drug UseInformation about prescription drug use was collected duringa household interview. Participants were asked if they hadtaken prescription drugs over the prior 30 days. Those whoresponded “yes” were asked to show the containers of allproducts; when unavailable, participants were asked toreport the medication name. For each drug reported, theinterviewer entered the information into a laptop computer,and the drug was linked to a prescription drug database(Lexicon Plus) that includes all prescription drugs available.This database was updated at the beginning of each surveyyear to include new products.
Most drug categories are classified as defined by theNational Center for Health Statistics (NCHS). Some additionaldefinitions were generated, including antihypertensives,noncontraceptive hormones, antibiotics (including oralantibiotic-containing medications and antibiotic-containingdermatologic, ophthalmic, and respiratory medications), andoral antibiotics. Subclasses of drugs within a given drug classare not presented if used by too few individuals to providereliable estimates on the prevalence of use. Medicationsdefined as combination drugs are included within both com-binations as well as their component drug categories to allowfor tracking of both combination drugs and specific drugclasses. For example, combination drugs containing adrener-gic bronchodilators are classified as adrenergic bronchodila-tors and also as bronchodilator combinations to allow forsimple quantification of trends in the use of medications con-taining adrenergic bronchodilators and also of combinationtherapies.
Statistical AnalysisThe prevalence of use within each 2-year NHANES cycle wasestimated for any prescription drug use and use by drug class.Polypharmacy was defined as use of at least 5 drugs, which in-dicates a threshold commonly used in the literature.18 Addi-tional results are presented for the most commonly used in-dividual drugs in 2011-2012. Survey-weighted logisticregression was used to calculate a P value for trend across sur-vey cycles. Statistical significance of trends was assessed at the2-sided α=.05 level. In the results presentation, data reportedas an increase refers to a P value for trend of less than .05 anda ratio greater than 1, a decrease refers to a P value for trend ofless than .05 and ratio of less than 1, and stable refers to aP value for trend of .05 or greater. We have also presented thedifference in prevalence in 2011-2012 vs 1999-2000, al-though these data, in some cases, may not represent the mostextreme difference in use across years
Because changes in the age distribution of the populationmay account for observed trends in prescription drug use,secondary age-adjusted analyses were conducted using stan-dardization based on the US 2000 Standard Population(eTable 1 in the Supplement).
Given potential for heterogeneity by population sub-groups, results were stratified by age (20-39 years, 40-64years, and ≥65 years), sex, and race/ethnicity (non-Hispanicwhite, non-Hispanic black, and Mexican American). Data forother race/ethnicity groups were not included in the strati-fied analyses due to insufficient sample sizes to reliably esti-mate the prevalence of use. Results are presented forMexican Americans rather than overall Hispanics because oftemporal changes in data collection among Hispanics.19 Addi-tional analyses evaluated race/ethnicity–stratified estimateswith adjustment for age (previously described) and with fur-ther adjustment for insurance coverage. In analyses adjustedfor both age and insurance, standardization was imple-mented using the age and insurance distribution of the 1999-2000 NHANES cycle. Given the large number of drug classesanalyzed, results for a given overarching drug class are dis-cussed if they meet any of the following criteria: (1) a greater
Prescription Drug Use in US Adults 1999-2012 Original Investigation Research
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than 10% prevalence of use in any cycle; (2) prevalence of usegreater than 5% with at least a 1.5-fold change; or (3) preva-lence of use greater than 2.5% with at least a 2-fold change inuse. This approach was selected to focus on commonly useddrugs and on modestly used drugs with notable trends.
For drugs meeting the previously described criteria, wehave calculated an average annual percentage change usingJoinpoint Statistical Software (version 4.2.0.2), which uses apermutation test to identify points of inflection (providing anannual percentage change (APC) before and after the point ofinflection [eTable 2 in the Supplement]).20,21
All analyses account for complex survey design and post-stratification weighting using Stata version 13.1.
Results
In these NHANES cycles, the response rate for adults aged 20years and older was 73.6%,22 and 84% of medication contain-ers were seen by interviewers. After excluding 65 individualswho did not have data on prescription drug use, the finalsample size was 37 959; the sample size for individual NHANEScycles ranged from 4861 to 6212.
Table 1 shows the estimated percentage of US adults re-porting use of any prescription medication in 2011-2012 andalso of those reporting use of 5 or more prescription medica-tions both overall and by population characteristics. Fifty-
Table 1. Prevalence of Prescription Drug Use in Prior 30 Days Among US Adults—2011-2012a
No. of Participants
No. (%) [95% CI]b
Any PrescriptionsPolypharmacy(≥5 Prescriptions)
Overall 5558 3144 (59) [55-62] 917 (15) [13-17]
Age group, y
20-39 1957 596 (35) [32-39] 47 (3.1) [2.1-4.6]
40-64 2352 1428 (65) [62-67] 372 (15) [13-17]
≥65 1249 1120 (90) [87-93] 498 (39) [35-44]
Sex
Men 2739 1398 (52) [48-57] 418 (13) [10-16]
Women 2819 1746 (65) [62-67] 499 (16) [14-19]
Race/ethnicity
White non-Hispanic 2040 1377 (66) [63-69] 440 (17) [15-20]
Black non-Hispanic 1455 835 (52) [49-55] 266 (14) [12-17]
Asian non-Hispanic 794 335 (41) [36-45] 54 (6) [4.0-8.7]
Mexican American 539 214 (33) [28-38] 56 (6.8) [4.2-10]
Other Hispanic 578 305 (41) [36-45] 77 (8.5) [6.0-12]
Other 152 78 (51) [38-63] 24 (17) [8.6-32]
Education
<High school 1331 806 (57) [50-64] 296 (19) [16-23]
High school 1169 658 (58) [53-64] 196 (15) [12-19]
Some college 1657 901 (57) [52-62] 264 (15) [13-19]
College 1396 776 (61) [57-65] 160 (12) [9.2-14]
Family income-to-poverty ratioc
<1 (Lowest income) 1303 677 (49) [43-54] 241 (16) [11-21]
1-<2 1326 755 (59) [52-65] 258 (18) [15-21]
2-<4 1167 662 (58) [51-64] 173 (15) [11-19]
≥4 (Highest income) 1267 760 (65) [60-69] 148 (12) [10-14]
Insurance status (age <65 y)d
No insurance 1259 369 (31) [25-38] 47 (3.6) [2.1-6.0]
Government only 872 544 (64) [59-70] 201 (21) [17-25]
Any private insurance 2175 1110 (57) [54-60] 171 (9.1) [7.5-11]
Body mass indexe
<18.5 103 50 (59) [50-68] 12 (18) [9.8-32]
18-<25 1577 768 (52) [48-57] 148 (8.4) [5.5-13]
25-<30 1684 939 (57) [52-62] 245 (12) [10-15]
30-<35 1066 1066 (62) [58-66] 212 (17) [15-19]
35-<40 451 284 (68) [60-75] 109 (24) [18-30]
≥40 354 250 (73) [66-78] 117 (29) [24-35]
a All paticipants were aged 20 yearsor older.
b The values for % (95% CI) areweighted to be nationallyrepresentative.
c Data were based on the federalpoverty level. In 2012, the federalpoverty level for a family of 4 was$22 050. A family of 4 with anincome of $40 000 would have afamily income-to-poverty ratio of1.81, indicating that their income is181% greater than the federalpoverty level.
d Information on insurance status wasobtained from the health insurancequestionnaire, assessing whetherthe individual was covered byhealth insurance at the time of thesurvey. Limited to adults who wereyounger than aged 65 since 98.9%of adults aged 65 years and olderreported having some form ofhealth insurance.
e Body mass index was calculated asweight in kilograms divided byheight in meters squared. Data wereavailable for 94.2% of respondents.Mobile Exam Center weights wereused for analyses of body massindex (interview analytic weightswere used in all other cases).
Research Original Investigation Prescription Drug Use in US Adults 1999-2012
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nine percent of adults used any prescription in the prior 30days, while 39% of adults aged 65 years and older reportedpolypharmacy. A significant increase in polypharmacy was ob-served in all 3 adult age groups: among those aged 20 to 39years, from 0.7% to 3.1%; among 40- to 64-year-olds, from 10%to 15%; and among those aged 65 years and older, from 24%to 39% (Figure 1).
From 1999-2000 to 2011-2012, the percentage of adults re-porting use of any prescription in the previous 30 days in-creased from an estimated 51% to 59% (difference, 8% [95%CI, 3.8%-12%]). Polypharmacy increased from an estimated8.2% to 15% (difference, 6.6% [95% CI, 4.4%-8.2%]; Figure 1
and Table 1). The increase in any prescription drug use and poly-pharmacy remained statistically significant in age-adjustedmodels (eTable 1 in the Supplement). Among the 18 drug classesused by more than 2.5% of the population, the prevalence ofuse increased in 11 drug classes (Table 2). All subsequent rangespresent prevalence of use in 1999-2000 vs 2011-2012 unlessspecified as otherwise.
Use of antihypertensives increased (20%-27%), with in-creases observed in most drug classes (Table 2). Antihyperlip-idemics use increased, a trend largely driven by statins (6.9%-17%). Use of statins increased markedly prior to 2005-2006(APC = 12%, after which the APC was 4.0%; eTable 2 in the
Figure 1. Trends in Any Prescription Drug Use and Use of 5 or More Prescription Drugs (Polypharmacy), Overall, and by Age Group, Sex,and Race/Ethnicity—1999-2012
80
60
40
20
100
80
60
40
20
100
60
40
20
80
100
0
Repo
rted
Use
in P
rior 3
0 Da
ys, %
YearNo. of participants20-39 y40-64 y≥65 y
1999-2000
169217871382
2001-2002
192520221452
2003-2004
173717991493
2005-2006
192318641183
2007-2008
191024691551
2009-2010
208126111520
2011-2012
195723521249
Reported by ageBAge 20-39 y
Any usePolypharmacy
Age 40-64 yAny usePolypharmacy
Age ≥65 yAny usePolypharmacy
Non-Hispanic whiteAny usePolypharmacy
Non-Hispanic blackAny usePolypharmacy
Mexican AmericanAny usePolypharmacy
80
60
40
20
100
0
Repo
rted
Use
in P
rior 3
0 Da
ys, %
YearNo. of participants
1999-2000
4861
2001-2002
5399
2003-2004
5029
2005-2006
4970
2007-2008
5930
2009-2010
6212
2011-2012
5558
All participantsA
0
Repo
rted
Use
in P
rior 3
0 Da
ys, %
YearNo. of participantsNon-Hispanic
WhiteBlack
MexicanAmerican
1999-2000
2210904
1280
2001-2002
285410101112
2003-2004
2686987985
2005-2006
249111201003
2007-2008
275812271032
2009-2010
297511211138
2011-2012
20401455
539
Reported by race/ethnicityD
0
Repo
rted
Use
in P
rior 3
0 Da
ys, %
YearNo. of participantsWomenMen
1999-2000
26002261
2001-2002
28672532
2003-2004
26172412
2005-2006
25872383
2007-2008
30212909
2009-2010
32103002
2011-2012
28192739
Reported by sexC
Any use
Polypharmacy
WomenAny usePolypharmacy
MenAny usePolypharmacy
All trends statistically significant except for any prescription drug use amongpersons aged 20 to39 years (P for trend = .22) and for any prescription drug use
among Mexican Americans (P for trend = .17). All data are weighted to benationally representative. Error bars indicate 95% CIs.
Prescription Drug Use in US Adults 1999-2012 Original Investigation Research
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9(0
.7-1
.2)
e.0
7N
AN
A
Antid
epre
ssan
ts6.
8(5
.8-7
.9)
9.1
(8.0
-10)
11(9
.9-1
2)11
(10-
12)
12(1
1-14
)11
(9.4
-12)
13(1
1-15
)<.
001
6.0
(3.5
to8.
6)1.
9(1
.5to
2.4)
Phen
ylpi
pera
zine
1.0
(0.8
-1.2
)1.
4(1
.0-1
.9)
1.0
(0.7
-1.4
)1.
0(0
.8-1
.4)
1.0
(0.8
-1.3
)0.
9(0
.7-1
.2)
1.3
(0.9
-1.7
).9
20.
3(−
0.1
to0.
7)1.
3(0
.92
to1.
9)
SSN
RIs
0.4
(0.3
-0.7
)0.
7(0
.4-1
.0)
1.1
(0.7
-1.7
)1.
9(1
.5-2
.5)
2.3
(1.8
-2.8
)1.
9(1
.5-2
.4)
2.0
(1.5
-2.6
)<.
001
1.6
(1.0
to2.
2)4.
7(2
.6to
8.5)
SSRI
s4.
3(3
.6-5
.2)
5.8
(5.1
-6.7
)7.
4(6
.5-8
.5)
7.0
(6.2
-7.9
)7.
3(6
.3-8
.4)
6.9
(5.6
-8.5
)8.
5(6
.9-1
0.4)
<.00
14.
2(2
.3to
6.1)
2.0
(1.5
to2.
6)
(con
tinue
d)
Research Original Investigation Prescription Drug Use in US Adults 1999-2012
1822 JAMA November 3, 2015 Volume 314, Number 17 (Reprinted) jama.com
Confidential. Do not distribute. Pre-embargo material.
Tabl
e2.
Tren
dsin
Pres
crip
tion
Dru
gU
sein
the
Prio
r30
Day
sAm
ong
US
Adul
tsby
Top
18–U
sed
Dru
gCl
asse
s—19
99-2
012
a(c
ontin
ued)
Prev
alen
ceof
Use,
%b
(95%
CI)
Pfo
rTr
end
2011
-201
2vs
1999
-200
0
1999
-200
0(n
=48
61)
2001
-200
2(n
=53
99)
2003
-200
4(n
=50
29)
2005
-200
6(n
=49
70)
2007
-200
8(n
=59
30)
2009
-201
0(n
=62
12)
2011
-201
2(n
=55
58)
Diff
eren
cein
Prev
alen
ce,
%(9
5%CI
)c
Ratio
ofPr
eval
ence
,Ra
tio(9
5%CI
)d
Tric
yclic
s1.
2(0
.9-1
.7)
1.5
(0.9
-2.3
)1.
5(1
.2-1
.9)
1.1
(0.9
-1.4
)1.
4(1
.2-1
.6)
1.0
(0.8
-1.5
)1.
3(1
.0-1
.8)
.59
0.1
(−0.
4to
0.7)
1.1
(0.7
2to
1.8)
Pres
crip
tion
anal
gesi
cs11
(10-
12)
13(1
2-14
)17
(15-
19)
12(1
0-13
)12
(10-
14)
12(1
0-13
)11
(9.2
-14)
.13
−0.1
(−2.
6to
2.5)
0.99
(0.7
9to
1.2)
COX-
2in
hibi
tors
1.9
(1.3
-2.7
)4.
3(3
.6-5
.0)
4.5
(3.8
-5.2
)1.
3(0
.8-2
.0)
1.0
(0.7
-1.6
)0.
5(0
.3-0
.7)
0.6
(0.4
-1.0
)<.
001
−1.3
(−2.
0to
−0.6
)0.
32(0
.17
to0.
59)
Nar
cotic
anal
gesi
cs3.
8(3
.1-4
.8)
4.5
(3.6
-5.6
)5.
8(4
.7-7
.2)
5.9
(4.9
-7.0
)5.
8(4
.5-7
.4)
5.1
(4.2
-7.6
)5.
7(4
.2-7
.6)
.05
1.8
(0.0
to3.
7)1.
5(1
.0to
2.1)
Pres
crip
tion
NSA
IDsf
5.6
(4.7
-6.6
)3.
7(3
.1-4
.4)
6.6
(5.6
-7.8
)4.
6(4
.0-5
.2)
4.2
(3.4
-5.1
)4.
5(3
.8-5
.2)
4.2
(3.4
-5.2
).0
3−1
.4(−
2.7
to−0
.1)
0.75
(0.5
7to
0.98
)
Salic
ylat
es0.
6(0
.4-0
.9)
0.7
(0.5
-0.9
)0.
5(0
.3-0
.8)
0.6
(0.5
-0.8
)1.
0(0
.7-1
.4)
1.5
(1.2
-2.0
)0.
6(0
.4-0
.9)
.002
0.0
(−0.
3to
0.3)
1.0
(0.5
8to
1.8)
Mis
cella
neou
san
alge
sics
0.4
(0.2
-0.7
)0.
4(0
.2-0
.6)
1.0
(0.7
-1.7
)0.
8(0
.5-1
.2)
1.1
(0.7
-1.6
)1.
3(1
.0-1
.7)
1.3
(1.0
-1.8
)<.
001
0.9
(0.4
to1.
4)3.
3(1
.8to
5.9)
Hor
mon
esg
Sex
19(1
6-21
)21
(18-
24)
14(1
3-16
)12
(11-
14)
12(1
0-14
)10
(8.6
-12)
11(8
.7-1
3)<.
001
−7.9
(−11
to−4
.6)
0.57
(0.4
5to
0.73
)
Cont
race
ptiv
e8.
1(6
.6-9
.8)
8.5
(6.7
-11)
7.0
(6.0
-8.3
)6.
9(5
.7-8
.3)
7.6
(5.8
-9.9
)7.
1(5
.9-8
.5)
7.1
(5.1
-9.9
).3
5−0
.9(−
3.8
to1.
9)0.
88(0
.60
to1.
3)
Non
cont
race
ptiv
e12
(10-
15)
14(1
2-16
)7.
2(6
.0-8
.7)
5.6
(4.8
-6.5
)4.
3(3
.2-5
.6)
3.1
(2.6
-3.8
)4.
0(3
.2-5
.1)
<.00
1−8
.5(−
11to
−5.6
)0.
32(0
.23
to0.
45)
Antid
iabe
ticag
ents
4.6
(3.8
-5.5
)5.
3(4
.5-6
.1)
6.4
(5.5
-7.5
)6.
4(5
.6-7
.3)
7.7
(6.5
-9.1
)7.
7(6
.8-8
.6)
8.2
(7.2
-9.3
)<.
001
3.6
(2.3
to5.
0)1.
8(1
.4to
2.2)
Bigu
anid
es2.
0(1
.5-2
.6)
2.5
(2.0
-3.1
)3.
6(3
.0-4
.3)
3.6
(2.9
-4.5
)4.
7(3
.9-5
.7)
4.9
(4.3
-5.7
)5.
5(4
.7-6
.4)
<.00
13.
5(2
.5to
4.5)
2.7
(2.0
to3.
7)
Insu
lin1.
1(0
.8-1
.6)
1.3
(0.9
-1.8
)1.
5(1
.2-1
.9)
1.6
(1.4
-1.9
)2.
1(1
.6-2
.8)
2.1
(1.6
-2.7
)2.
6(2
.2-3
.1)
<.00
11.
5(0
.9to
2.1)
2.3
(1.6
to3.
3)
Sulfo
nylu
reas
2.6
(2.2
-3.2
)2.
7(2
.3-3
.1)
3.3
(2.6
-4.1
)2.
9(2
.3-3
.6)
3.3
(2.8
-3.8
)3.
0(2
.6-3
.5)
3.2
(2.5
-4.2
)<.
001
0.6
(−0.
4to
1.5)
1.2
(0.8
8to
1.7)
Thia
zolid
ined
ione
s0.
5(0
.3-0
.8)
0.9
(0.7
-1.2
)2.
0(1
.7-2
.4)
2.0
(1.5
-2.6
)1.
9(1
.4-2
.4)
1.2
(1.0
-1.6
)0.
8(0
.6-1
.1)
.17
0.3
(−0.
1to
0.7)
1.6
(0.8
6to
2.9)
Pres
crip
tion
prot
on-p
ump
inhi
bito
rs3.
9(3
.0-5
.0)
6.2
(5.5
-7.1
)7.
5(6
.4-8
.7)
8.0
(6.7
-9.5
)9.
0(7
.4-1
1)9.
3(8
.0-1
1)7.
8(6
.2-9
.6)
<.00
13.
9(1
.9to
5.9)
2.0
(1.4
to2.
8)
Thyr
oid
horm
ones
5.1
(4.4
-5.9
)5.
2(4
.5-6
.0)
7.0
(6.1
-8.0
)7.
1(6
.0-8
.3)
6.7
(5.9
-7.6
)7.
1(6
.2-8
.3)
6.4
(5.3
-7.7
).0
071.
3(−
0.2
to2.
7)1.
2(0
.98
to1.
6)
Anxi
olyt
ics,
seda
tives
,hy
pnot
ics
4.2
(3.4
-5.1
)4.
4(3
.7-5
.2)
6.1
(4.6
-7.9
)5.
5(4
.8-6
.4)
6.5
(5.5
-7.7
)6.
1(5
.4-6
.8)
6.1
(5.0
-7.3
)<.
001
1.9
(0.5
to3.
3)1.
5(1
.1to
1.9)
Benz
odia
zepi
nes
2.8
(2.2
-3.5
)3.
2(2
.6-3
.8)
4.2
(3.1
-5.6
)3.
4(2
.9-4
.0)
3.8
(3.1
-4.6
)3.
8(3
.1-4
.6)
3.9
(3.3
-4.8
).0
41.
1(0
.2to
2.1)
1.4
(1.0
to1.
9)
Antic
onvu
lsan
ts2.
3(1
.9-2
.9)
3.5
(2.8
-4.3
)4.
5(3
.7-5
.5)
4.3
(3.7
-5.0
)5.
3(4
.5-6
.3)
5.3
(4.8
-5.8
)5.
5(4
.6-6
.6)
<.00
13.
2(2
.0to
4.3)
2.3
(1.8
to3.
1)
Benz
odia
zepi
nes
1.2
(0.9
-1.7
)1.
6(1
.1-2
.1)
2.1
(1.5
-2.9
)1.
8(1
.5-2
.2)
1.9
(1.6
-2.3
)2.
1(1
.7-2
.7)
2.3
(1.8
-2.9
).0
021.
1(0
.4to
1.7)
1.8
(1.3
to2.
7)
γ-Am
inob
utyr
icac
idan
alog
se
0.9
(0.7
-1.2
)1.
2(0
.8-1
.8)
1.2
(0.8
-1.7
)1.
9(1
.4-2
.5)
1.9
(1.6
-2.3
)2.
1(1
.6-2
.7)
<.00
11.
8(1
.2to
2.4)
7.4
(2.8
to19
)
Bron
chod
ilato
rs3.
2(2
.6-4
.0)
3.3
(2.6
-4.2
)3.
9(3
.1-4
.8)
4.4
(3.7
-5.2
)5.
1(4
.3-5
.9)
4.7
(3.8
-5.7
)5.
2(4
.0-6
.6)
<.00
11.
9(0
.5to
3.4)
1.6
(1.1
to2.
2)
Adre
nerg
icbr
onch
odila
tors
2.9
(2.3
-3.6
)3.
2(2
.5-4
.1)
3.7
(3.0
-4.5
)4.
2(3
.6-5
.0)
4.9
(4.1
-5.7
)4.
4(3
.6-5
.3)
4.9
(3.7
-6.3
)<.
001
2.0
(0.5
to3.
4)1.
7(1
.2to
2.4)
Antic
holin
ergi
cbr
onch
odila
tors
0.6
(0.5
-0.7
)0.
5(0
.4-0
.7)
1.1
(0.8
-1.6
)0.
9(0
.7-1
.2)
1.3
(1.0
-1.8
)1.
0(0
.7-1
.5)
1.1
(0.8
-1.6
)<.
001
0.5
(0.1
to1.
0)1.
9(1
.2to
3.0)
(con
tinue
d)
Prescription Drug Use in US Adults 1999-2012 Original Investigation Research
jama.com (Reprinted) JAMA November 3, 2015 Volume 314, Number 17 1823
Confidential. Do not distribute. Pre-embargo material.Ta
ble
2.Tr
ends
inPr
escr
iptio
nD
rug
Use
inth
ePr
ior3
0D
aysA
mon
gU
SAd
ults
byTo
p18
–Use
dD
rug
Clas
ses—
1999
-20
12a
(con
tinue
d)
Prev
alen
ceof
Use,
%b
(95%
CI)
Pfo
rTr
end
2011
-201
2vs
1999
-200
0
1999
-200
0(n
=48
61)
2001
-200
2(n
=53
99)
2003
-200
4(n
=50
29)
2005
-200
6(n
=49
70)
2007
-200
8(n
=59
30)
2009
-201
0(n
=62
12)
2011
-201
2(n
=55
58)
Diff
eren
cein
Prev
alen
ce,
%(9
5%CI
)c
Ratio
ofPr
eval
ence
,Ra
tio(9
5%CI
)d
Bron
chod
ilato
rco
mbi
natio
ns0.
3(0
.2-0
.4)
0.6
(0.4
-0.8
)1.
9(1
.4-2
.5)
1.9
(1.4
-2.4
)2.
2(1
.7-2
.7)
2.1
(1.5
-2.9
)2.
1(1
.4-3
.0)
<.00
11.
8(1
.0to
2.6)
7.9
(4.6
to14
)
Antib
iotic
s5.
7(5
.1-6
.3)
5.6
(4.5
-6.9
)5.
5(4
.8-6
.3)
5.4
(4.5
-6.4
)4.
3(3
.8-4
.8)
4.0
(3.4
-4.7
)4.
2(3
.7-4
.9)
<.00
1−1
.4(−
2.3
to−0
.6)
0.75
(0.6
3to
0.90
)
Ora
lant
ibio
tics
3.8
(3.2
-4.4
)3.
6(2
.9-4
.5)
3.7
(3.1
-4.4
)3.
4(2
.6-4
.4)
2.8
(2.3
-3.3
)2.
7(2
.3-3
.2)
2.9
(2.5
-3.3
)<.
001
−0.9
(−1.
6to
−0.1
)0.
77(0
.63
to0.
96)
Antia
rrhy
thm
icag
ents
4.9
(4.5
-5.4
)4.
5(3
.8-5
.3)
4.3
(3.7
-5.0
)4.
5(3
.8-5
.3)
3.4
(2.8
-4.1
)3.
0(2
.5-3
.7)
2.7
(2.1
-3.5
)<.
001
−2.2
(−3.
0to
−1.4
)0.
55(0
.42
to0.
73)
Clas
sIV
2.7
(2.4
-2.9
)2.
4(1
.9-2
.9)
2.1
(1.7
-2.6
)2.
2(1
.8-2
.8)
1.3
(1.0
-1.6
)1.
4(1
.1-1
.8)
1.0
(0.6
-1.5
)<.
001
−1.7
(−2.
2to
−1.2
)0.
52(0
.30
to0.
89)
Clas
sV1.
4(1
.1-1
.8)
1.0
(0.8
-1.3
)1.
1(0
.8-1
.5)
0.9
(0.6
-1.3
)0.
7(0
.5-0
.9)
0.5
(0.3
-1.0
)0.
7(0
.4-1
.0)
<.00
1−0
.8(−
1.2
to−0
.3)
0.83
(0.4
2to
1.6)
Coag
ulat
ion
mod
ifier
s2.
3(1
.9-2
.8)
2.6
(2.1
-3.1
)3.
3(2
.6-4
.2)
3.8
(3.1
-4.8
)4.
8(4
.1-5
.6)
4.8
(3.9
-5.8
)4.
0(3
.4-4
.8)
<.00
11.
8(0
.9to
2.6)
1.8
(1.4
to2.
3)
Antic
oagu
lant
s1.
3(0
.9-1
.8)
1.5
(1.2
-1.9
)1.
4(1
.1-1
.9)
1.7
(1.5
-2.0
)1.
9(1
.4-2
.6)
1.8
(1.4
-2.4
)1.
7(1
.3-2
.1)
.04
0.4
(−0.
2to
1.0)
1.3
(0.8
7to
2.0)
War
farin
1.3
(0.9
-1.8
)1.
4(1
.1-1
.8)
1.4
(1.1
-1.9
)1.
7(1
.5-2
.0)
1.9
(1.4
-2.6
)1.
8(1
.4-2
.3)
1.5
(1.1
-2.1
).1
00.
3(−
0.3
to0.
9)1.
2(0
.79
to1.
9)
Antip
late
let
agen
ts0.
9(0
.7-1
.2)
1.1
(0.8
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omen
.
Research Original Investigation Prescription Drug Use in US Adults 1999-2012
1824 JAMA November 3, 2015 Volume 314, Number 17 (Reprinted) jama.com
Confidential. Do not distribute. Pre-embargo material.Supplement). Use of antidepressants increased (6.8%-13%),reflected by an increase in use of selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) (0.4%-2.0%) andalso in selective serotonin reuptake inhibitors (SSRIs) (4.3%-8.5%). Use of antidepressants increased most in the early years,driven by a sharp increase in SSNRIs before 2005-2006(APC = 32%), after which time, the trend leveled off (APC,−0.2%).
Prescription analgesic use remained stable (11%), al-though trends differed by type. Use of cyclooxygenase-2(COX-2) inhibitors decreased from 1.9% to 0.6%, while theprevalence of narcotic analgesic use increased from 3.8% to5.7%. Notably, narcotic analgesics increased before 2003-2004 (APC=12%), after which time, the use stabilized (APC,−1.2%).
Use of sex hormones among women decreased from 19%to 11%, which was a change primarily driven by a decline in useof noncontraceptive hormones (12.0%-4.0%, a drug class com-posed largely of menopausal hormone therapy). Use ofantidiabetic agents increased from 4.6% to 8.2%, specifi-cally, increases were observed for biguanides, insulin, and sul-fonylureas. Although use of thiazolidinediones remained un-changed overall, a significant inflection point was observed in2003-2004 (before which, use increased [APC = 48%], and af-ter which, use decreased [APC, −8.8%]).
An increase was reported in the use of prescription proton-pump inhibitors (PPIs) (3.9%-7.8%) and also the use of anti-convulsants (2.3%-5.5%). Notably, the use of anticonvulsantsincreased most in the early years with an APC of 16% ob-served before 2003-2004, and an APC of 3.0% was observedthereafter. Use of bronchodilators increased (3.2%-5.2%) over-all, with use of adrenergic bronchodilators increasing most be-fore 2007-2008 (APC = 6.6%) and stabilizing afterwards (APC,−1.2%). Use of bronchodilator combinations increased sharplybefore 2003-2004 (APC = 66%), and were reported with an APC2.2% afterwards. Further, use of muscle relaxants increased(1.2%-2.5%), with the increase sharpest in the periods be-tween 1999-2000 and 2003-2004 (APC prior to 2003-2003,19%; thereafter, −1.7%). Use of antibiotics decreased from 5.7%to 4.2% over the study period. Trends of use for prescriptiondrug classifications with a prevalence of use less than 2.5% arereported in Table 3.
Prescription drug use increased significantly among per-sons aged 40 to 64 years (57%-65%) and also among those aged65 years and older (84%-90%) (Table 4), but not among adultsaged 20 to 39 years (32%-35%) (Figure 1, panel B). For specificdrug classes, trends were generally similar by age and sex withsome exceptions (eg, use of prescription analgesics did notchange among adults aged 40-64 years [13%-14%], but use sig-nificantly decreased among adults aged ≥65 years [18%-14%]; use of muscle relaxants increased significantly amongwomen [1.2%-3.3%], but did not increase significantly amongmen [1.3%-1.7%]) (Table 4 and Table 5; eTables 3 and 4 in theSupplement).
Although significant increases in the percentage of per-sons using 5 or more prescriptions were observed in all racial/ethnic groups (eTable 5 in the Supplement), an overall in-crease in prescription drug use was evident among individuals
who were non-Hispanic white (55%-66%) and non-Hispanicblack (43%-52%), but not Mexican American (30%-33%). Thispattern remained unchanged with age adjustment, and theprevalence of use among individuals who were Mexican Ameri-can remained markedly lower than among that of those whowere non-Hispanic white (although the difference was attenu-ated somewhat; eTable 6 in the Supplement). Further sensi-tivity analyses revealed that this difference in any prescrip-tion use was not entirely attributable to adjustment forinsurance status, although race/ethnicity–specific differ-ences in polypharmacy were attenuated (eTable 6 and eTable7 in the Supplement).
The most commonly used individual drug in 2011-2012 wassimvastatin (7.9%), increasing from 2.0% in 1999-2000 (eTable8 in the Supplement and Figure 2). The remaining top 10 drugsincluded lisinopril, levothyroxine, metoprolol, metformin, hy-drochlorothiazide, omeprazole, amlodipine, atorvastatin, andalbuterol; all of the top 10 most commonly used drugs in-creased over the study period except atorvastatin.
DiscussionOverall, prescription drug use increased among US adults be-tween 1999-2000 and 2011-2012, as reflected by an increasein any prescription drug use and a marked increase in poly-pharmacy. Specifically, the prevalence of prescription drug useincreased from 51% in 1999-2000 to 59% in 2011-2012, whilethe prevalence of polypharmacy increased from 8.2% to 15%.The increase in prescription drug use was observed for the ma-jority of but not all drug classes.
Use of antihypertensive drugs increased over the study pe-riod, with a marked increase observed for several antihyper-tensives, including thiazide diuretics. The increase in use ofthiazide diuretics is notable, given the recommendations fortheir use as first-line agents by the 2003 JNC 7 (Seventh Re-port of the Joint National Committee on Prevention, Detec-tion, Evaluation, and Treatment of High Blood Pressure).24
However, in trend analyses accounting for potential inflec-tion points the APC was highest before 2003-2004, suggest-ing that the increase in thiazide diuretics use preceded ratherthan resulted from the 2003 recommendations. In 2014, theJNC 8 guidelines relaxed recommendations for drug initia-tion and expanded the options for first-line drug therapy, whichmay further influence the landscape of antihypertensive use.25
Use of antihyperlipidemics increased markedly, drivenprimarily by an increase in use of statins, for which the great-est increase was observed prior to 2005-2006. Although useof both simvastatin and atrovastatin increased early in thestudy period, use of atorvastatin started to decline after2005-2006. This pattern likely reflects the fact that simvasta-tin came off patent in 2006 while atorvastatin remained pat-ent protected, and therefore more costly, until 2011. Notably,this study preceded the release of the 2013 American Collegeof Cardiology/American Heart Association recommendations,which expanded guidelines for statin use.26
The increase in use of antidepressant drugs may, in part,reflect shifting attitudes regarding depression.27 Use of SSRIs
Prescription Drug Use in US Adults 1999-2012 Original Investigation Research
jama.com (Reprinted) JAMA November 3, 2015 Volume 314, Number 17 1825
Confidential. Do not distribute. Pre-embargo material.Ta
ble
3.Tr
ends
inPr
escr
iptio
nD
rug
Use
inth
ePr
ior3
0D
aysA
mon
gU
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ults
byLe
sser
-Use
dD
rug
Clas
ses—
1999
-20
12a
Prev
alen
ceof
Use,
%b
(95%
CI)
Pfo
rTr
end
2011
-201
2vs
1999
-200
0
1999
-200
0(n
=48
61)
2001
-200
2(n
=53
99)
2003
-200
4(n
=50
29)
2005
-200
6(n
=49
70)
2007
-200
8(n
=59
30)
2009
-201
0(n
=62
12)
2011
-201
2(n
=55
58)
Diff
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cein
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0.9
(0.7
-1.1
)1.
0(0
.7-1
.5)
0.7
(0.5
-1.1
)0.
7(0
.4-1
.3)
0.9
(0.6
-1.2
)0.
6(0
.4-0
.9)
0.6
(0.4
-1.0
).0
6−0
.3(−
0.6
to0.
1)0.
70(0
.40
to1.
2)
Sele
ctiv
ees
trog
enre
cept
or-m
odul
ator
s1.
1(0
.8-1
.6)
1.6
(1.2
-2.1
)1.
4(1
.0-2
.1)
1.4
(0.9
-2.0
)1.
4(1
.0-1
.8)
1.0
(0.7
-1.5
)f
.01
−0.3
(−0.
6to
0.0)
0.54
(0.2
6to
1.1)
Abbr
evia
tions
:CN
S,ce
ntra
lner
vous
syst
em.
aAl
ldat
aar
ew
eigh
ted
tobe
natio
nally
repr
esen
tativ
e.O
vera
rchi
ngdr
ugcl
asse
sare
pres
ente
din
orde
rof
desc
endi
ngpr
eval
ence
in20
11-2
012
.Pre
vale
nce
ofus
efo
rdru
gcl
asse
srep
orte
din
this
tabl
ew
ere
less
than
2.5%
atal
ltim
epo
ints
durin
gth
est
udy
perio
d.b
Prev
alen
ceva
lues
of10
%an
dgr
eate
rare
roun
ded
toth
ene
ares
twho
lenu
mbe
r.c
Indi
cate
sthe
abso
lute
incr
ease
orde
crea
sein
prev
alen
ceof
use
betw
een
1999
-20
00
and
2011
-20
12.
dIn
dica
test
here
lativ
ein
crea
seor
decr
ease
inpr
eval
ence
ofus
ebe
twee
n19
99-2
00
0an
d20
11-2
012
.e
Anal
yses
limite
dto
men
.f
Dat
aw
ithhe
lddu
eto
rela
tive
stan
dard
erro
rofg
reat
erth
an30
%in
resu
ltsfo
ragi
ven
surv
eycy
cle,
cons
isten
tw
ithN
HAN
ES(N
atio
nalH
ealth
and
Nut
ritio
nEx
amin
atio
nSu
rvey
)ana
lytic
guid
elin
es.23
Research Original Investigation Prescription Drug Use in US Adults 1999-2012
1826 JAMA November 3, 2015 Volume 314, Number 17 (Reprinted) jama.com
Confidential. Do not distribute. Pre-embargo material.
Tabl
e4.
Tren
dsin
Use
ofSe
lect
edPr
escr
iptio
nD
rugs
inth
ePr
ior3
0D
aysA
mon
gU
SAd
ults
byAg
eGr
oup—
1999
-20
12a
Aged
40-6
4Ye
ars
Aged
≥65
Year
sPr
eval
ence
ofUs
e,%
(95%
CI)
Pfo
rTr
end
2011
-201
2vs
1999
-200
0Pr
eval
ence
ofUs
e,%
(95%
CI)
Pfo
rTr
end
2011
-201
2vs
1999
-200
0
1999
-200
0(n
=17
87)
2011
-201
2(n
=23
52)
Diff
eren
cein
Prev
alen
ce,
%(9
5%CI
)b
Ratio
ofPr
eval
ence
,Ra
tio(9
5%CI
)c19
99-2
000
(n=
1382
)20
11-2
012
(n=
1249
)
Diff
eren
cein
Prev
alen
ce,
%(9
5%CI
)b
Ratio
ofPr
eval
ence
,Ra
tio(9
5%CI
)c
Any
pres
crip
tion
57(5
2-63
)65
(62-
67)
.01
7.4
(1.7
to13
)1.
1(1
.0to
1.2)
84(8
1-86
)90
(87-
93)
<.00
16.
5(2
.8to
10)
1.1
(1.0
to1.
1)
≥5Pr
escr
iptio
ns10
(8.8
-12)
15(1
3-17
).0
024.
4(1
.8to
6.9)
1.4
(1.2
to1.
7)24
(21-
26)
39(3
5-44
)<.
001
16(1
0to
21)
1.7
(1.4
to1.
9)
Antih
yper
tens
ive
agen
ts24
(21-
28)
31(2
8-33
)<.
001
6.4
(2.0
to11
)1.
3(1
.1to
1.5)
55(5
0-59
)66
(62-
69)
<.00
111
(5.9
to17
)1.
2(1
.1to
1.3)
Antih
yper
lipid
emic
agen
ts11
(8.9
-13)
21(1
8-24
)<.
001
10(6
.5to
14)
2.0
(1.6
to2.
4)21
(17-
25)
47(4
4-51
)<.
001
27(2
2to
32)
2.3
(1.9
to2.
7)
Antid
epre
ssan
ts8.
4(7
.0-1
0)15
(13-
18)
<.00
16.
9(3
.9to
9.8)
1.8
(1.4
to2.
3)8.
4(6
.8-1
0)17
(13-
22)
<.00
18.
8(4
.3to
13)
2.0
(1.5
to2.
8)
Pres
crip
tion
anal
gesi
cs13
(12-
15)
14(1
1-18
).2
70.
4(−
3.3
to4.
2)1.
0(0
.79
to1.
3)18
(16-
21)
14(1
1-18
).0
1−3
.9(−
8.4
to0.
7)0.
79(0
.59
to1.
1)
Sex
horm
ones
d24
(19-
29)
9.7
(7.5
-12)
<.00
1−1
4(−
20to
−8.8
)0.
41(0
.28
to0.
53)
16(1
2-22
)3.
9(2
.0-7
.5)
<.00
1−1
3(−
18to
−7.3
)0.
24(0
.08
to0.
40)
Antid
iabe
ticag
ents
5.5
(4.2
-7.3
)9.
4(7
.9-1
1)<.
001
3.9
(1.7
to6.
1)1.
7(1
.3to
2.3)
13(1
1-15
)19
(17-
22)
<.00
16.
5(3
.4to
9.7)
1.5
(1.3
to1.
8)
Pres
crip
tion
prot
on-p
ump
inhi
bito
rs4.
9(3
.4-7
.1)
8.3
(5.8
-12)
.006
3.4
(0.0
to6.
7)1.
7(1
.0to
2.7)
8.2
(6.4
-10)
18(1
4-22
)<.
001
9.6
(5.4
to14
)2.
2(1
.6to
2.9)
Thyr
oid
horm
ones
5.9
(4.6
-7.4
)6.
9(5
.1-9
.2)
.13
1.0
(−1.
4to
3.4)
1.2
(0.8
2to
1.7)
13(1
1-17
)15
(12-
18)
.25
1.6
(−2.
7to
5.8)
1.1
(0.8
4to
1.5)
Anxi
olyt
ics,
seda
tives
,hy
pnot
ics
5.5
(4.1
-7.3
)6.
7(5
.1-8
.7)
.17
1.2
(−1.
2to
3.6)
1.2
(0.8
3to
1.8)
8.6
(6.8
-11)
9.3
(7.7
-11)
.52
0.7
(−1.
9to
3.4)
1.1
(0.8
1to
1.4)
Antic
onvu
lsan
ts3.
1(2
.1-4
.8)
5.8
(4.3
-7.8
).0
022.
7(0
.5to
4.8)
1.8
(1.1
to3.
0)4.
5(3
.5-5
.8)
9.0
(6.5
-12)
<.00
14.
5(1
.5to
7.4)
2.0
(1.4
to2.
9)
Bron
chod
ilato
rs3.
4(2
.5-4
.5)
6.0
(4.0
-8.7
).0
022.
6(0
.1to
5.1)
1.8
(1.1
to2.
8)6.
3(4
.2-9
.2)
7.3
(5.8
-9.2
).1
41.
1(−
1.8
to3.
9)1.
2(0
.77
to1.
8)
Antib
iotic
s5.
9(4
.5-7
.6)
3.7
(2.5
-5.6
).0
09−2
.1(−
4.2
to−0
.1)
0.64
(0.4
0to
1.0)
4.4
(3.2
-6.0
)3.
5(2
.2-5
.4)
.01
−0.9
(−2.
9to
1.1)
0.80
(0.4
7to
1.3)
Antia
rrhy
thm
icag
ents
5.4
(4.7
-6.2
)2.
1(1
.6-2
.7)
<.00
1−3
.3(−
4.3
to−2
.4)
0.38
(0.2
8to
0.51
)17
(14-
19)
9.0
(6.9
-12)
<.00
1−7
.5(−
11to
−4.0
)0.
54(0
.40
to0.
74)
Coag
ulat
ion
mod
ifier
s2.
7(1
.9-3
.8)
2.8
(1.9
-3.9
).0
20.
0(−
1.3
to1.
3)1.
0(0
.64
to1.
6)7.
0(5
.6-8
.9)
15(1
3-18
)<.
001
7.9
(5.0
to11
)2.
1(1
.6to
2.8)
Mus
cle
rela
xant
s1.
8(1
.1-2
.9)
3.4
(2.4
-4.7
).0
41.
6(0
.2to
3.0)
1.9
(1.1
to3.
3)1.
1(0
.6-1
.9)
2.6
(0.9
-7)
.19
1.5
(−1.
2to
4.2)
2.4
(0.7
9to
7.2)
H 2An
tago
nist
s1.
9(1
.2-2
.9)
2.2
(1.2
-4)
.34
0.3
(−1.
2to
1.8)
1.2
(0.5
8to
2.4)
5.8
(3.7
-9.1
)4.
9(3
.3-7
.1)
.45
−0.9
(−4.
0to
2.2)
0.84
(0.4
8to
1.5)
Pres
crip
tion
antih
ista
min
es4.
6(3
.3-6
.3)
2.0
(1.3
-2.9
)<.
001
−2.6
(−4.
2to
−1.0
)0.
43(0
.27
to0.
69)
3.9
(2.7
-5.4
)3.
3(1
.9-5
.6)
.09
−0.6
(−2.
7to
1.6)
0.85
(0.4
6to
1.6)
Antie
met
ic/a
ntiv
ertig
oag
ents
2.6
(1.7
-3.8
)2.
1(1
.3-3
.3)
.54
−0.5
(−1.
8to
0.9)
0.81
(0.4
6to
1.4)
3.8
(2.1
-6.6
)3.
6(2
.4-5
.6)
.38
−0.1
(−2.
7to
2.4)
0.97
(0.4
9to
1.9)
Gluc
ocor
ticoi
ds2.
7(2
.1-3
.5)
1.8
(1.2
-2.8
).0
1−0
.9(−
1.9
to0.
1)0.
66(0
.41
to1.
1)3.
8(2
.7-5
.2)
2.4
(1.7
-3.4
).0
2−1
.4(−
2.8
to0.
1)0.
64(0
.41
to1.
0)a
Resu
ltsfo
radu
ltsag
ed20
-39
year
sare
notp
rese
nted
beca
use
ofsm
alln
umbe
rs(s
eeeT
able
3in
the
Supp
lem
ent)
.Ove
rarc
hing
drug
clas
sesa
repr
esen
ted
inor
dero
fdes
cend
ing
prev
alen
cein
2011
-20
12.A
lldat
aar
ew
eigh
ted
tobe
natio
nally
repr
esen
tativ
e.b
Indi
cate
sthe
abso
lute
incr
ease
orde
crea
sein
prev
alen
ceof
use
betw
een
1999
-20
00
and
2011
-20
12.
cIn
dica
test
here
lativ
ein
crea
seor
decr
ease
inpr
eval
ence
ofus
ebe
twee
n19
99-2
00
0an
d20
11-2
012
.d
Anal
yses
limite
dto
wom
en.
Prescription Drug Use in US Adults 1999-2012 Original Investigation Research
jama.com (Reprinted) JAMA November 3, 2015 Volume 314, Number 17 1827
Confidential. Do not distribute. Pre-embargo material.Ta
ble
5.Tr
ends
inU
seof
Sele
cted
Pres
crip
tion
Dru
gsin
the
Prio
r30
Day
sAm
ong
US
Adul
tsby
Sex—
1999
-20
12a
Men
Wom
enPr
eval
ence
ofUs
e,%
(95%
CI)
Pfo
rTr
end
2011
-201
2vs
1999
-200
0Pr
eval
ence
ofUs
e,%
(95%
CI)
Pfo
rTr
end
2011
-201
2vs
1999
-200
0
1999
-200
0(n
=22
61)
2011
-201
2(n
=23
52)
Diff
eren
cein
Prev
alen
ce,
%(9
5%CI
)b
Ratio
ofPr
eval
ence
,Ra
tio(9
5%CI
)c19
99-2
000
(n=
1382
)20
11-2
012
(n=
1249
)
Diff
eren
cein
Prev
alen
ce,
%(9
5%CI
)b
Ratio
ofPr
eval
ence
,Ra
tio(9
5%CI
)c
Any
pres
crip
tion
42(3
9-45
)52
(48-
57)
<.00
111
(5.4
to16
)1.
3(1
.1to
1.4)
59(5
5-63
)65
(62-
67)
.03
5.7
(0.7
to11
)1.
1(1
.0to
1.2)
≥5Pr
escr
iptio
ns5.
8(5
.2-6
.6)
13(1
0-16
)<.
001
7.2
(4.3
to10
)2.
2(1
.8to
2.8)
10(9
.0-1
2)16
(15-
19)
<.00
16.
0(3
.5to
8.6)
1.6
(1.3
to1.
9)
Antih
yper
tens
ive
agen
ts18
(16-
21)
26(2
3-30
)<.
001
8.0
(3.6
to12
)1.
4(1
.2to
1.7)
21(1
8-24
)29
(26-
32)
<.00
17.
7(3
.9to
12)
1.4
(1.2
to1.
6)
Antih
yper
lipid
emic
agen
ts8.
6(7
.4-1
0)19
(16-
22)
<.00
110
(7.3
to14
)2.
2(1
.8to
2.7)
6.7
(5.8
-7.7
)18
(15-
20)
<.00
111
(8.5
to14
)2.
7(2
.2to
3.2)
Antid
epre
ssan
ts4.
1(3
.1-5
.4)
8.8
(7.2
-11)
<.00
14.
8(2
.6to
6.9)
2.2
(1.6
to3.
0)9.
3(7
.7-1
1)17
(14-
20)
<.00
17.
2(3
.6to
11)
1.8
(1.4
to2.
3)
Pres
crip
tion
anal
gesi
cs9.
4(8
.0-1
1)9.
7(7
.6-1
2).7
30.
2(−
2.5
to3.
0)1.
0(0
.78
to1.
4)13
(11-
15)
13(1
0-16
).0
4−0
.4(−
3.5
to2.
8)0.
97(0
.76
to1.
2)
Antid
iabe
ticag
ents
4.6
(3.5
-6.0
)9.
1(7
.7-1
1)<.
001
4.5
(2.6
to6.
4)2.
0(1
.5to
2.7)
4.6
(3.7
-5.8
)7.
4(6
.2-8
.8)
<.00
12.
8(1
.2to
4.4)
1.6
(1.2
to2.
0)
Pres
crip
tion
prot
on-p
ump
inhi
bito
rs3.
4(2
.3-4
.9)
7.0
(5.1
-9.4
)<.
001
3.6
(1.1
to6.
0)2.
1(1
.3to
3.3)
4.3
(3.3
-5.7
)8.
5(6
.6-1
1)<.
001
4.2
(1.8
to6.
6)2.
0(1
.4to
2.8)
Thyr
oid
horm
ones
2.0
(1.3
-3.0
)3.
2(2
.3-4
.6)
.04
1.2
(−0.
2to
2.7)
1.6
(0.9
6to
2.8)
8.0
(6.7
-9.4
)9.
3(7
.8-1
1).0
21.
3(−
0.7
to3.
3)1.
2(0
.93
to1.
5)
Anxi
olyt
ics,
seda
tives
,hy
pnot
ics
3.0
(2.2
-4.3
)5.
3(4
.0-7
.0)
.002
2.3
(0.5
to4.
1)1.
8(1
.2to
2.7)
5.2
(4.1
-6.6
)6.
8(5
.4-8
.5)
.01
1.5
(−0.
4to
3.5)
1.3
(0.9
4to
1.8)
Antic
onvu
lsan
ts1.
8(1
.3-2
.4)
4.9
(3.9
-6.2
)<.
001
3.1
(1.9
to4.
4)2.
8(1
.9to
3.9)
2.8
(2.0
-3.9
)6.
0(4
.8-7
.6)
<.00
13.
2(1
.5to
4.8)
2.1
(1.5
to3.
1)
Bron
chod
ilato
rs2.
3(1
.6-3
.2)
5.0
(3.6
-6.9
).0
012.
7(0
.9to
4.5)
2.2
(1.4
to3.
4)4.
1(3
.0-5
.5)
5.3
(4.0
-6.9
).0
061.
2(−
0.6
to3.
1)1.
3(0
.88
to1.
9)
Antib
iotic
s4.
6(3
.8-5
.6)
3.7
(2.7
-5.0
).0
47−0
.9(−
2.3
to0.
5)0.
79(0
.56
to1.
1)6.
6(5
.4-8
.0)
4.8
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Research Original Investigation Prescription Drug Use in US Adults 1999-2012
1828 JAMA November 3, 2015 Volume 314, Number 17 (Reprinted) jama.com
Confidential. Do not distribute. Pre-embargo material.and SSNRIs markedly increased; notably, use of SSNRIs in-creased between 1999-2000 and 2005-2006, remaining stablethereafter. Even so, SSRIs remain much more commonly usedthan the other antidepressant drugs, and the continued popu-larity of the SSRIs may reflect the availability of several ge-neric options with a wide range of indications and a favorableprofile regarding adverse effects.28
Overall, trends in analgesic use were stable; however, therewas marked heterogeneity by class. Use of COX-2 inhibitors de-creased, likely a result of rofecoxib being taken off the marketin 2004.29 Conversely, use of narcotic analgesic drugs in-creased from 1999-2000 to 2011-2012. Although increased useof narcotic analgesics may raise concern about their potentialmisuse or abuse, it should be noted that use stabilized after2003-2004. This flattening trend may reflect increased aware-ness of prescription opioid drug misuse or abuse,30 althoughunderreporting of these drugs may have increased with aware-ness regarding their potential for abuse.
Use of sex hormones decreased substantially amongwomen, resulting from the decrease in noncontraceptive hor-mone use (following the release of results from the Women’sHealth Initiative Hormone Therapy Trial).10,31 This decrease isnotable because conjugated estrogens once represented themost commonly used prescription drug.11
As the prevalence of diabetes increased,32 use of antidia-betic drugs also increased, driven by a sharp rise in use of in-sulin and biguanides. Accordingly, metformin, considered afirst-line agent in the treatment of diabetes,33 is now the fifthmost commonly used drug. Use of thiazolidinediones de-creased in recent years, likely owing to concern regarding thelink between rosiglitazone and risk of cardiovascular events.34
Despite certain proton-pump inhibitors becoming avail-able over the counter (OTC), use of prescription proton-pump inhibitors increased, a trend which would be likely evenmore marked if we were able to account for OTC use. The in-crease in prescription proton-pump inhibitors may, in part, re-flect the availability of more affordable varied options for pro-ton-pump inhibitors following the loss of patent protection foromeprazole in 2001 and subsequent market entry of esome-prazole. It remains unclear how use of prescription proton-pump inhibitors will be affected long term by increasing avail-ability of OTC proton-pump inhibitors.
Use of anticonvulsant drugs increased over the studyperiod. Several anticonvulsants are cross-classified in otherdrug classes (eg, benzodiazepines), and it is likely that thesealternative indications are in part driving the observedincrease in use.
A significant inflection point was observed for use of ad-renergic bronchodilators in 2007-2008, after which time usestabilized. It is possible that this pattern may in part reflect the2005 US Food and Drug Administration’s Public Health Advi-sory regarding use of long-acting β2-adrenergic agonists. Thesharp early increase in use of bronchodilator combinations mayreflect other market forces, including direct-to-consumer ad-vertising (DCTA), which peaked in the mid-2000s.35,36 DCTAis particularly relevant to bronchodilator combinations suchas the popular combination drug Advair, which was ranked asone of the top drugs in terms of DCTA in 2010.36 Even so, a re-
cent study found little evidence of association between DCTAand Advair prescriptions, and it therefore seems unlikely thatDCTA alone is responsible.37
Use of muscle relaxants increased over the study period.Although the reasons underlying this increase are unclear, therehas been discussion about the potential for misuse or abuseof carisoprodol, one of the more commonly used muscle re-laxants. In 2011, the Drug Abuse Warning Network released areport showing an increase in emergency department visits as-sociated with carisoprodol between 2004 and 2009,38 and in2012, the Drug Enforcement Administration classified this drugas a controlled substance. Notably, however, in our data, thesharpest increase in prevalence of use of muscle relaxants wasobserved before 2003-2004, with no significant change ob-served thereafter.
The increases in any prescription drug use and polyphar-macy are not explained by changes in the age distribution ofthe population. An alternative explanation for the observed in-crease in prescription drug use might be large-scale policychanges, including the implementation of Medicare Part D.However, the increase in prescription drug use was not ob-served only among adults aged 65 years and older but alsoamong adults aged 40 to 64 years. Furthermore, MedicarePart D went into effect in 2006, and for many of the drug classesdiscussed, the sharpest increase occurred before 2006.
It is unclear if this pattern, with the sharpest increases ob-served early in the study period, reflects a saturation of the mar-ket, the peak of DCTA in the mid-2000s,36 or lagged effects re-sulting from the increase in obesity in the population. Eightof the 10 most commonly used drugs in 2011-2012 are used totreat components of the cardiometabolic syndrome, includ-ing hypertension, diabetes, and dyslipidemia. Another is a pro-ton-pump inhibitor used for gastroesophageal reflux, a con-dition more prevalent among individuals who are overweight
Figure 2. Trends in Individual Prescription Medications UsedBy More Than 4% of US Adults—2011-2012
8
6
4
2
10
0
Repo
rted
Use
in P
rior 3
0 Da
ys, %
Year
No. ofparticipants
1999-2000
4861
2001-2002
5399
2003-2004
5029
2005-2006
4970
2007-2008
5930
2009-2010
6212
2011-2012
5558
SimvastatinLisinoprilLevothyroxineMetoprololMetforminHydrochlorothiazideOmeprazole
All trends were statistically significant (P for trend for each drug < .001). All dataare weighted to be nationally representative. Error bars indicate 95% CIs.
Prescription Drug Use in US Adults 1999-2012 Original Investigation Research
jama.com (Reprinted) JAMA November 3, 2015 Volume 314, Number 17 1829
Confidential. Do not distribute. Pre-embargo material.or obese.39 Thus, the increase in use of some agents may re-flect the growing need for treatment of complications associ-ated with the increase in overweight and obesity.
For most drugs and drug classes, trends were generallycomparable across age, sex, and race/ethnicity. One majordifference was that any prescription drug use was substan-tially lower for Mexican American than for non-Hispanicwhite individuals. Because the Mexican American popula-tion is younger than the non-Hispanic white population,40
we conducted age-adjusted analyses and found that amarked difference between groups persisted, although thedifference attenuated somewhat. Further adjustment forinsurance status did not entirely account for the difference inany prescription use, although it is possible that prescriptiondrug coverage may better account for the observed pattern.An alternative explanation may be the Hispanic paradox,which is that despite lower socioeconomic status, individualsof Hispanic descent have better-than-expected health status,which would likely result in less use of prescriptionmedications.41 The reasons underlying these differences arelikely multifactorial, meriting further investigation.
We have provided a comprehensive picture of prescrip-tion drug use in the US adult population using nationally rep-resentative data. Prescription drug use was assessed viain-home interviews in which containers were seen for 84% of
drugs, giving confidence to participants’ self-reported use.Further, NHANES has a high response rate, reducing concernabout bias. Even so, this study has several limitations. First,recall of intermittently used drugs may be more prone tomeasurement error than drugs used daily. Second, we areunable to capture OTC drug use, and some trends, such asthe decrease in antihistamines use, reflect the availability ofcertain drugs becoming available OTC. Third, this survey wasconducted among noninstitutionalized adults; thus, resultsdo not capture use among adults living in nursing homes andshould only be generalized to the community-dwelling USadult population. Additionally, certain drugs may be in morethan one class and some drugs may be taken for off-label use,and therefore, the classifications of drugs do not perfectlyalign with reasons for use.
ConclusionsIn this nationally representative survey, significant increasesin overall prescription drug use and polypharmacy were ob-served. These increases persisted even after accounting forchanges in the age distribution of the population. The preva-lence of prescription drug use increased in the majority of butnot all drug classes.
ARTICLE INFORMATION
Author Affiliations: Department of Epidemiology,Harvard T. H. Chan School of Public Health, Boston,Massachusetts (Kantor, Giovannucci); Departmentof Epidemiology and Biostatistics, Memorial SloanKettering Cancer Center, New York, New York(Kantor); Friedman School of Nutrition Science andPolicy, Tufts University, Boston, Massachusetts(Rehm); Office of Community & Population Health,Montefiore Medical Center, Bronx, New York(Rehm); Division of General Internal Medicine andPrimary Care, Brigham and Women’s Hospital,Boston, Massachusetts (Haas); Department ofSocial and Behavioral Sciences, Harvard T. H. ChanSchool of Public Health, Boston, Massachusetts(Haas); Channing Division of Network Medicine,Brigham and Women's Hospital, Boston,Massachusetts (Chan, Giovannucci); Division ofGastroenterology, Massachusetts General Hospital,Boston (Chan); Clinical and TranslationalEpidemiology Unit, Massachusetts GeneralHospital, Boston (Chan); Department of Nutrition,Harvard T. H. Chan School of Public Health, Boston,Massachusetts (Giovannucci).
Author Contributions: Drs Kantor and Rehm hadfull access to all of the data in the study and takeresponsibility for the integrity of the data and theaccuracy of the data analysis. Both authorscontributed equally to this article.Study concept and design: Kantor, Rehm, Chan.Acquisition, analysis, or interpretation of data:Kantor, Rehm, Haas, Chan, Giovannucci.Drafting of the manuscript: Kantor, Rehm, Chan.Critical revision of the manuscript for importantintellectual content: Rehm, Haas, Chan,Giovannucci.Statistical analysis: Kantor, Rehm, Giovannucci.Study supervision: Haas, Chan, Giovannucci.
Conflict of Interest Disclosures: All authors havecompleted and submitted the ICMJE Form forDisclosure of Potential Conflicts of Interest. Dr Chanreports having consulted for Pfizer Inc, BayerHealthcare, and Pozen Inc.
Funding/Support: This work was conducted withsupport from the National Cancer Institute (supportfor Kantor, T32 CA 009001) and the NationalInstitute of Diabetes and Digestive and KidneyDiseases (support for Chan, K24 DK098311).Support for Haas: Harvard Catalyst—The HarvardClinical and Translational Science Center (NationalCenter for Research Resources and the NationalCenter for Advancing Translational Sciences,National Institutes of Health Award UL1 TR001102)and financial contributions from Harvard Universityand its affiliated academic health care centers.
Role of the Funder/Sponsor: The funder had norole in the design and conduct of the study;collection, management, analysis, andinterpretation of the data; and preparation, review,or approval of the manuscript; or the decision tosubmit the manuscript for publication.
Disclaimer: The content is solely the responsibilityof the authors and does not necessarily representthe official views of Harvard Catalyst, HarvardUniversity and its affiliated academic health carecenters, or the National Institutes of Health.
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