PEDIATRICS Vol. 122 No. 5 November 2008, pp. e1053-e1061 (doi:10.1542/peds.2008-0214)
ARTICLE |
Trends in the Prevalence of Chronic Medication Use in Children: 2002–2005
a Express Scripts, Inc, St Louis, Missouri
b Pediatric Research Institute, St Louis University, St Louis, Missouri
c Kansas Health Institute, Topeka, Kansas
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ABSTRACT |
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OBJECTIVE. Our goal was to estimate the quarterly prevalence of and evaluate trends for chronic medication use in children.
PATIENTS AND METHODS. A cross-sectional study of ambulatory prescription claims data from 2002 to 2005 was conducted for a nationally representative sample of >3.5 million commercially insured children who were 5 to 19 years old. Prevalence of chronic medication use was measured quarterly for antihypertensives, antihyperlipidemics, type 2 antidiabetics, antidepressants, attention-deficit disorder and attention-deficit/hyperactivity disorder medications, and asthma-controller therapy.
RESULTS. First-quarter 2002 baseline prevalence of chronic medication use per 1000 child beneficiaries ranged from a high of 29.5 for antiasthmatics to a low of 0.27 for antihyperlipidemics. Except for asthma medication use, prevalence rates were higher for older teens aged 15 to 19 years. During the study period, the prevalence rate for type 2 antidiabetic agents doubled, driven by 166% and 135% increases in prevalence among females aged 10 to 14 and 15 to 19 years, respectively. Therapy classes with double-digit growth in prevalence of use were asthma medications (46.5%), attention-deficit disorder and attention-deficit/hyperactivity disorder medications (40.4%), and antihyperlipidemics (15%). Prevalence of use growth was more moderate for antihypertensives and antidepressants (1.8%). Rates of growth were dramatically higher among girls than boys for type 2 antidiabetics (147% vs 39%), attention-deficit disorder and attention-deficit/hyperactivity disorder medications (63% vs 33%), and antidepressants (7% vs –4%).
CONCLUSIONS. Prevalence of chronic medication use in children increased across all therapy classes evaluated. Additional study is needed into the factors influencing these trends, including growth in chronic disease risk factors, greater awareness and screening, and greater affinity toward early use of drug therapy in children.
Key Words: prescription drugs • chronic disease • prevalence • pediatrics
Abbreviations: ADD—attention-deficit disorder • ADHD—attention-deficit/hyperactivity disorder • ACE—angiotensin-converting enzyme inhibitors • ARB—angiotensin II receptor antagonists • CCB—calcium channel blockers • FDA—Food and Drug Administration
A growing body of evidence has documented the increased risk for and prevalence of chronic conditions in children including obesity,1 hypertension,2 diabetes,3 and asthma.4 Although the National Children's Study is a significant effort to understand the underlying etiology of disease in children, little is understood about existing treatment regimens, particularly drug therapy, for children with chronic conditions. Nonpharmacological treatment is considered first line for many chronic conditions in children; however, drug therapy is also recommended.5–11 Excepting drug therapy for attention-deficit disorder (ADD) and attention-deficit/hyperactivity disorder (ADHD) and depression,12–15 patterns of prescription drug use to treat chronic conditions in children are not well understood. The purpose of this study was to evaluate trends in the prevalence of chronic medication use within a population of commercially insured children aged 5 to 19 years.
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METHODS |
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Data represented ambulatory administrative pharmacy claims and eligibility information for commercially insured children enrolled with Express Scripts, Inc (St Louis, MO) between 2002 and 2005. Express Scripts administers pharmacy benefit services to >1300 plan sponsors representing >50 million members. Plan sponsors included in the analysis offered both a subsidized prescription benefit and integrated (home delivery and retail) pharmacy benefits within an employer-based market (ie, no Medicare or Medicaid).
Chronic drug therapy classes were identified as those with primary use for an ongoing health condition as defined by Stein and colleagues,16 were used to treat prevalent chronic conditions in children and where treatment would occur primarily in the outpatient setting. Those therapy classes selected included drugs used to treat hypertension, hyperlipidemia, type 2 diabetes, depression, ADD or ADHD, and asthma (Table 1). Therapy classes were identified by using the Generic Product Identifier code.17
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As profiled in Table 1, 5 antihypertensive drug classes were evaluated. The central
-blockers (eg, clonidine) were excluded because they are also used for treating ADD/ADHD in children.11 Asthma drugs included the controller medications18 but excluded short-acting β-agonists because of their frequent use for conditions other than asthma. Quarterly prevalence was calculated by dividing the number of children with at least 1 prescription claim in the therapy class by the average number of children 5 to 19 years old enrolled within that quarter. Average enrollment was calculated as the total number of months children were enrolled each quarter divided by 3 months. Estimates of prevalence were calculated overall, by gender, and across 3 age categories: 5 to 9, 10 to 14, and 15 to 19 years. Age was calculated at the beginning of each quarter. The quarterly trend was estimated by using time series analysis controlling for first-order autocorrelation (SPSS 12.0 [SPSS Inc, Chicago, IL]). The total increase in prevalence over the 4-year period was estimated by multiplying the slope coefficient for the quarter by 16 (4 quarters per year x 4 years). The percentage change in prevalence of use was estimated by dividing the overall increase in prevalence by the relevant intercept term from the regression equations. Including all children enrolled during a given quarter eliminated possible selection bias from including only children continually enrolled in that quarter.
This study was not submitted to an outside institutional review board. However, the Health Insurance Portability and Accountability Act regulations regarding use of personal health information were followed.
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RESULTS |
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More than 3 million children were included in each sample year, and the distribution of girls and boys was consistent across the age categories (Table 2). Baseline quarterly prevalence estimates per 1000 child beneficiaries are presented in Table 3. The highest prevalence rates were for medications used to treat asthma (29.5), ADD/ADHD (25.4), and depression (15.7). Baseline prevalence use was <3 per 1000 child beneficiaries for antihypertensives and <1 per 1000 for antihyperlipidemics and type 2 antidiabetic agents. Within the antihypertensive therapy class, β blockers had the highest prevalence of use at 1.12 followed by angiotensin converting enzyme inhibitors (ACEs)/angiotensin II receptor antagonists (ARBs) at 0.65. Calcium channel blockers (CCBs) had the lowest prevalence of use at 0.33 per 1000 child beneficiaries.
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Several patterns in baseline prevalence of use across age groups are notable. First, for antihypertensives, lipid-lowering agents, type 2 antidiabetics, and antidepressants, prevalence for children aged 15 to 19 years was at least 2 times greater than children aged 10 to 14 years and 3 times greater than children aged 5 to 9 years. ADD/ADHD use was higher among children aged 10 to 14 years and asthma prevalence use was highest for children aged 5 to 9 years of age.
Differences in baseline prevalence between males and females were not as disparate. Females had a 2 times higher rate than males for type 2 antidiabetic medications. In contrast, prevalence of use for ADD/ADHD medications in males was 3 times the rate in females. Prevalence of asthma medications was 1.5 and 1.3 times greater among boys aged 5 to 9 and 10 to 14 years, respectively, compared with their female counterparts.
Trends in Prevalence of Use
Estimated trends from 2002 through 2005 are presented in Table 3 and in Figs 1 through 6. Prevalence rate trends ranged from a low of 1.8% for any antihypertensive use to a high of 103% for type 2 antidiabetics. Compared with boys, girls had markedly higher use trends for type 2 antidiabetics (147% vs 38.7%), ADD/ADHD (62.6% vs 33.1%), and antidepressants (7.2% vs –3.8%).
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Driving the 103% increase in type 2 antidiabetic drug use were increases of 166% and 135% among 10- to 14-year-old and 15- to 19-year-old girls, respectively. Asthma-controller drug use grew at a rate of 46.5%, with rates among children aged 5 to 9 years double that of older children. Antihyperlipidemic prevalence use grew by 15%, with the highest rate of growth (24.2%) noted among girls aged 15 to 19 years. The 63% increase in ADD/ADHD medication use in females was driven by a 114% increase among 15- to 19-year-olds.
The overall trend in antidepressant prevalence use was <2%, with use among girls increasing at 7% but use for males decreasing (–3.8%). Girls aged 15 to 19 years not only had the highest baseline prevalence, they also drove the overall trend among girls with a 7% increase. As seen in Fig 4, prevalence of use increased from 2002 through the first quarter of 2004, then declined across all age groups, leaving the overall trend relatively flat through 2005.
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For any antihypertensive use, overall prevalence increased by 2% with a negative 2% trend in girls and a positive 6% trend in boys. The highest rate of increase (15%) was in boys aged 15 to 19 years old. Across the studied antihypertensive therapy classes, overall prevalence of use increased for ACEs/ARBs and diuretics, but decreased for CCBs and β blockers. The greatest rate of growth, >41% from 2002 to 2005, was in the ACE/ARB therapy class among boys aged 15 to 19 years old. For diuretics, overall increased prevalence was driven by double-digit growth among 15- to 19-year-olds. Among children younger than 15 years, the rate of growth remained flat or decreased across all antihypertensive therapy classes.
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DISCUSSION |
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Antihypertensives
Overall, girls had higher rates of drug use than boys. Big influences were the greater rates of β blocker use (1.6 times) and diuretic use (3 times) in girls compared with boys aged 15 to 19 years. These findings are inconsistent with disease prevalence rates that show males have higher prevalence rates of hypertension than females.2,19,20
The overall rate of growth across all antihypertensive therapies was 2% from first-quarter 2002 to fourth-quarter 2005. That the largest increases were seen in children aged 15 to 19 may reflect increased rates of hypertension as a developing comorbidity in obese teenagers, as well as increased screening and treatment for hypertension among older teens. These increasing trends in prescription use are consistent with recent national trends that show prevalence of hypertension has increased among 8- to 17-year-olds.2,21
The first and second "Report of the Task Force on Blood Pressure Control in Children" recommended diuretics and β blockers as first-line therapy in the treatment of hypertension.22,23 However, the fourth report in 2005 places choice of initial antihypertensive therapy "in the preference of the responsible physician."10 Our findings of increased ACE/ARB therapy and decreased use of CCBs and β blockers suggest that physician preferences were changing before the revised guidelines were published. The decreased use of β blockers likely is related to their numerous contraindications,24 including their use in children with asthma. In addition, the use of β blockers may increase the risk of type 2 diabetes and mask the symptoms of hypoglycemia in those with established diabetes; these risks would reduce their use in overweight patients.25 The lower growth rate of ACEs/ARBs in girls relative to boys may result from potential teratogenic effects, such as profound fetal hypotension, renal tubular dysplasia, and anuria-oligohydramnios, which limit their use in females of childbearing age.26 The persistent growth rate of diuretics in female adolescents is particularly concerning given their known potential for abuse in eating-disorder patients.27
Antihyperlipidemics
Prevalence of use for antihyperlipidemics was the lowest among all therapy classes evaluated with modest growth from 2002 to 2005. Boys had higher overall baseline rates of antihyperlipidemic drug use compared with girls. Driven by growth among older teens, prevalence of use grew at a similar rate of 14% to 15% among boys and girls. Given the links between obesity and elevated serum cholesterol levels, rising use of antihyperlipidemics could be related to increases in obesity rates among children.28,29
Hyperlipidemia prevalence among male and female adolescents is mixed. Among a sample of eighth-grade adolescents in 3 US locations, prevalence was not significantly different between boys and girls.20 However, in a sample of >9000 children aged 5 to 17 years in Bogalusa, Louisiana, significantly higher total non–high-density lipoprotein cholesterol levels were noted in girls than boys.29
The 1992 National Cholesterol Education Program guidelines for the diagnosis and treatment of elevated cholesterol in children8 recommended drug therapy in children aged 
10 years only after failure of at least 6 months of diet therapy and low-density lipoprotein cholesterol remaining at 190 mg/dL or low-density lipoprotein cholesterol remaining at >160 mg/dL and other risk factors predisposing a child to cardiovascular events. Drug treatment recommended at that time included the bile acid sequestrants, cholestyramine, and colestipol. Other lipid-lowering agents, including statins, were not recommended for routine use. Updated guidelines released in 1998 reiterated this position on drug therapy.7 Shortly thereafter, clinical trials provided evidence of the safety and effectiveness of statins in pediatric patients, resulting in 4 statins receiving pediatric indications by 2002. Within our sample, market share for the statin therapy class was 68% in 2005 although the American Heart Association did not recommend statins as first-line therapy in the treatment of lipid abnormalities in children until 2007.6
Type 2 Antidiabetics
This study found that girls had a 1.8-fold greater baseline rate of type 2 antidiabetic drug use compared with boys. The increased trends in prevalence among girls (146% vs 39% in boys) resulted in a threefold greater rate of antidiabetic drug use in girls compared with boys by the end of 2005. Although girls represent a larger proportion of adolescents with type 2 diabetes (prevalence of 0.18% among girls and 0.12% among boys),30 the higher disease rates in girls do not approach the differences in drug use prevalence.
The prevalence of type 2 antidiabetic prescription use among children more than doubled from 2002 to 2005, driven by the rise in use among 10- to 14- and 15- to 19-year-old females. Obesity is known to be 1 of the key risk factors for type 2 diabetes in children31–33 with overweight and obese children approximately twice as likely as normal-weight children to develop the disease.34 However, patterns of prescription use between males and females are not consistent with obesity patterns. Noted in this study was a greater prevalence of type 2 antidiabetic drug use and greater increase in prevalence among teenaged girls, although the greater rates of and growth in obesity from the 1999–2000 to 2003–2004 National Health and Nutrition Examination Survey were found in boys aged 6 to 11 and 12 to 19 years.1 Therefore, obesity alone does not explain these prescribing patterns.
One factor contributing toward relatively greater rates of type 2 antidiabetic prescription use in females may be use of metformin to treat polycystic ovary syndrome, overweight, and/or metabolic syndrome, although the use of metformin in these conditions is still controversial.35–38 In addition, the higher rates in older female children may also be related to the almost double rate of physician office visits for females aged 15 to 24 years compared with males in the same age group.39
The increased rate of antidiabetic drug use may be associated with greater overall rates of screening among children at risk. However, only one fifth of clinicians are estimated to follow the American Diabetes Association's recommendation to screen for type 2 diabetes in moderate and children at high risk.40 Within a hospital-based urban care system, fewer than half of adolescents who should have been screened were screened based on a retrospective chart review.41 Additional study is necessary to understand the dramatic increase in type 2 antidiabetic medication use, particularly in females.
Antidepressants
In the first quarter of 2002, 16 per 1000 child beneficiaries were prescribed an antidepressant. The rate was highest among 15- to 19-year-old females, with 3.4 of every 100 having at least 1 antidepressant prescription claim in the first quarter of 2002. The higher prescription rate among older female teens is consistent with studies that have examined prevalence of depression in similar age groups.42
Overall prevalence of antidepressant use among all children increased through the first quarter of 2004, then decreased (Fig 4). The initial increase in prevalence seems to be a continuation of the 9.2% adjusted annual increase in the prevalence of antidepressant use among children 18 years and younger reported in an earlier study, which used pharmacy claims data from 1998 to 2002.13 Similar to the earlier findings, our study found the greatest use and increases in prevalence for older teenaged girls. Although early increases in prescription prevalence were believed to be associated with increased prevalence of depression in children, researchers found no evidence of increased prevalence from 1965 to 1996.42 This suggests that better recognition of and screening for depression in children may be 1 driver of prescription use trends. Other factors contributing to increased trends are expanded Food and Drug Administration (FDA) indications for serotonin reuptake inhibitors to treat conditions such as obsessive compulsive disorder and anxiety.
Antidepressant use began to decline in the second quarter of 2004 in response to the FDA's October 2003 release of a public heath advisory indicating suicidal thinking and worsening of depression in children taking certain antidepressants.43 Despite the public health advisory, prevalence of use in females aged 15 to 19 years continued at a modest rate.
ADD/ADHD
In the first quarter of 2002, prescription prevalence rates for ADD/ADHD medications were 3 times greater in males than females across all age groups. Consistently, unadjusted disease prevalence rates in a nationally representative US sample of children aged 8 to 15 years, were significantly higher in boys (11.8%) than girls (5.4%).44
For females, however, rates of growth from 2002 to 2005 were approximately double those of males resulting in a narrowing of the gap from a 3.1 to a 2.5 male/female ratio by the end of 2005. Several reasons may explain this trend. By 2002, studies had suggested that the prevalence of inattentive-type ADHD, much less likely to be identified and treated, was higher in females than males,45 possibly leading to increased efforts by physicians to identify ADHD in females. In addition, some studies suggest internalizing behaviors and psychological symptoms among adolescent girls with ADHD are more common relative to younger girls and adolescent boys with ADHD.46–48 This may lead to increased referral for psychological care in adolescent girls, which allows for the diagnosis of ADHD to be made.
Asthma
In first-quarter 2002, the overall baseline prevalence of asthma-controller medication was higher among males, except for 15- to 19-year-olds, whose rate of use was similar between females and males. Rates were lower among older teens, which may be explained by multiple factors including parental concerns about long-term adverse effects, less reliance on controller therapy, and more reliance on short-acting β agonists because of decreased frequency and severity of the disease, and/or increased tolerance to asthma symptoms by adolescents and their caregivers.49
Prevalence of asthma-controller therapy had the second highest overall rate of growth among all therapy classes evaluated from 2002 to 2005. Contributing to this growth are guidelines that continue to recommend early and aggressive asthma treatment.18 Released in 2002, the guidelines, which concentrate on the long-term management of asthma in children, recommend inhaled corticosteroids for mild or moderate persistent asthma. Shifts in drug use patterns from recommended guidelines and increases in disease prevalence linked to increased rates of obesity among children may also contribute.50,51
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LIMITATIONS |
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Studies have found prescription claims data to be a reliable and valid source of data.52,53 However, limitations of these data do exist. Changes in prevalence rates from 2002 to 2005 could also be influenced by changes in the mix of plan sponsors over the period. Additions or losses of large plan sponsors with higher or lower than average prevalence rates could bias trending. We believe that this impact is mitigated because no 1 client represented >6% of total child beneficiaries in any 1 year. In addition, 61% of plan sponsors, representing 71% of child beneficiaries in 2002, were included in the 2005 sample.
With this study we evaluated utilization among commercially insured children. Therefore, generalizing study findings to uninsured or lower income children (eg, Medicaid or State Child Health Insurance Programs) is limited. In addition, use for the therapy classes evaluated is assumed to be for selected approved chronic conditions of interest. Prevalence rates and trends may be influenced by off-label use, such as certain antidepressants for pain disorders or anxiety, or secondary use, such as propranolol for migraine prophylaxis. Limited data are available to indicate how these uses may affect our results. Additional research incorporating diagnoses should examine the extent of off-label or secondary use within these chronic therapy classes.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONLIMITATIONSCONCLUSIONSREFERENCES |
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This study, in which we examined trends in prescription drug therapy to treat chronic conditions in children, revealed increasing prevalence of use across all therapy classes evaluated. Varying patterns were noted between males and females and across age groups. Particularly noteworthy are growing rates of use among female children, at times rates twice as great as among males. These findings hold important implications for children's health and health care costs in the United States.
Some of these patterns reflect changes in physician prescribing, although increases in prevalence may also be because of increases in risk factors for chronic diseases, increased screening rates, or greater use of drug therapy as the preferred treatment for children with chronic conditions. Another factor contributing toward increased prevalence of use is federal legislation spurring research on the safety and efficacy of selected drug therapy in children. Specifically the voluntary pediatric exclusivity provision of the FDA Modernization Act of 1997 (and the FDA's "pediatric rule"). The FDA Modernization Act of 1997 provided incentives for pharmaceutical manufacturers to conduct studies in children, whereas the FDA's pediatric rule required manufacturers to test their products in children for selected new drugs and biologics. The response to the provisions exceeded expectations with 
100 medications receiving pediatric indications between 1998 and 2005.54 This increased data on safety and efficacy in children likely provided physicians with a greater degree of confidence to prescribe in pediatric populations.
Although these patterns of use provide important insights into the treatment decisions of physicians and probable links to chronic disease risk factors, such as obesity, key questions remain. Additional research is necessary to determine the reasons for greater rates of treatment and growth in the use of drug therapy among female children relative to males. Also, research should examine the implications of these changing trends on overall child health. Although drug therapy is effective for treating many chronic conditions in children, the risk of inappropriate use also exists. As chronic prescription use grows, so too do the risks of drug-related adverse effects and drug–drug interactions. Although research is underway to understand the etiology of chronic disease in children, addressing the appropriateness of current treatment patterns must not be ignored.
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FOOTNOTES |
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Accepted Jul 9, 2008.
Address correspondence to Emily R. Cox, RPh, PhD, One Express Way, St Louis, MO 63121. E-mail: ecox{at}express-scripts.com
The authors have indicated they have no financial relationships relevant to this article to disclose.
| What's Known on This Subject Studies that have examined the use of chronic medication in children are limited. Researchers have examined prevalence of use of antidepressants and ADD and ADHD drugs in children.
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| What This Study Adds We examined the prevalence of and trends for the use of chronic therapies: antihypertensives, lipid-lowering drugs, asthma medications, and antidiabetic agents.
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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
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