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Pediatric Stimulant and Selective Serotonin Reuptake Inhibitor Prescription Trends
1992 to 1998
Jerry L. Rushton, MD, MPH;
J. Timothy Whitmire, PhD
Arch Pediatr Adolesc Med. 2001;155:560-565.
ABSTRACT
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Background Presciption trends have key implications for costs, outcomes, and research,
yet few data exist on pediatric selective serotonin reuptake inhibitor (SSRI)
trends and associations with stimulant trends.
Objective To describe prescription trends for stimulants, SSRIs, and combination
prescriptions by age, sex, and race.
Methods Retrospective population-based analysis of North Carolina Medicaid prescription
claims files.
Participants North Carolina Medicaid recipients, 1992 through 1998, aged 1 to 19
years. The population ranged from 342 333 children in 1992 to 581 088
in 1998.
Main Outcome Measures Annual number of prescriptions, patients filling a prescription claim,
and prescription prevalence for stimulants and SSRIs.
Results The number of children and adolescents who received stimulants increased
from 6407 (24 584 claims) in 1992 to 27 951 (135 057 claims)
in 1998. The number of SSRI recipients increased from 510 children (1326 claims)
in 1992 to 6984 children (25 392 claims) in 1998. Prescription prevalence
in school-aged children 6 to 14 years increased from 4.4% to 9.5% for stimulants
during the study period, and from 0.2% to 1.5% for SSRIs. In 1998, stimulant
prescription prevalence was highest for white school-aged males (18.3%) vs
black females (3.4%) and SSRI prescription prevalence was highest for white
school-aged males (2.8%) vs black females (0.6%). Combination pharmacotherapy
also increased during 1992 through 1998.
Conclusions Prevalence of stimulant and SSRI medications has increased during the
1990s, with prescription prevalence in North Carolina Medicaid youth higher
than previously reported. Age, sex, and racial differences are apparent and
call for further attention. Combination pharmacotherapy also has growing importance.
INTRODUCTION
INCREASES IN psychotropic prescriptions for children and adolescents
have generated considerable controversy in the medical literature and popular
press. Most of the debate has centered on issues of safety, effectiveness,
and prescription patterns for methylphenidate and other stimulants used in
the treatment of attention-deficit/hyperactivity disorder.1, 2, 3
Stimulant prescriptions increased rapidly during the 1970s and 1980s, rising
from 1.1% of public elementary students receiving medication for attention-deficit/hyperactivity
disorder in 1971 to 6.0% of students in 1987.4
Although stimulant prescriptions may have temporarily decreased to 3% around
1990,5 subsequent studies documented continuing
increases through 1995, with prescription prevalence of 3.6% to 4.9%.2, 3, 6, 7
Stimulants and selective serotonin reuptake inhibitors (SSRIs), a subclass
of antidepressants, are the 2 most common types of psychotropic medications
prescribed to children,8 yet few studies have
reported SSRI prescription trends in pediatric populations.8, 9, 10
Since the SSRIs were introduced in 1988, physicians have been prescribing
these medications for children, with SSRIs now constituting half of all antidepressant
prescriptions.10 Jensen et al8
reported approximately 6 million stimulant drug mentions and 1 million SSRI
mentions in the 1995 National Disease and Therapeutic Index for children younger
than 18 years and a similar relative percentage of stimulant to SSRI prescriptions
in the 1995 National Ambulatory Medical Care Survey. However, denominators
from these data are limited and prevalences are difficult to interpret for
the pediatric age groups. Prescriptions of SSRIs for children and adolescents
have been described in other large pharmaceutical databases as part of broader
studies on pediatric psychotropics,8, 9, 10, 11, 12, 13
but no studies have reported SSRI figures with demographic information for
a defined pediatric population.
Studies on prescription trends and prescriber practices are important
to understand changes in care and to guide research initiatives on medication
labeling, information, and safety. Concerns of potential adverse effects have
been raised in particular regarding the off-label use of pediatric medications
and the practice of prescribing medications for younger preschool children.12, 13, 14, 15, 16, 17
Polypharmacy or combination psychotropic therapy is another practice used
for adult patients that has also been reported in pediatric patients.13, 14, 18, 19 Concerns
of pediatric medication safety and efficacy in pediatric dosing are compounded
when multiple medications are used together for off-label indications or in
very young children.20 In addition to safety,
psychotropic prescription trends and changes in mental health care also have
important implications for the cost of care. Mental health care accounts for
a significant percentage of total medical spending for children younger than
18 years.21, 22 New psychotropic
medications like the SSRIs are expensive, yet cost studies of SSRI use in
adults have not been documented for pediatric patients.23
The purpose of our study was to describe prescription trends for the
2 most commonly prescribed classes of psychotropic medications: the stimulants
and SSRIs. We sought to document the number of prescription claims, the number
of Medicaid patients prescribed these medications, prescription prevalence
by age group, and then to describe trends of the 2 classes of medications
over time. We wanted to determine if increases reported in other studies also
occurred in our population of interest and, if so, whether increases in prescription
prevalence have continued throughout the 1990s. An additional aim was to examine
how often these medications are prescribed in combination. Finally, we were
interested in describing trends of sex, age, and racial differences for Medicaid
children receiving these psychotropic medications.
MATERIALS AND METHODS
We queried the State of North Carolina Medicaid Database for all prescription
claims filled between January 1, 1992, and December 31, 1998, for children
aged 1 to 19 years. The study period was selected to provide the most current
information available with complete claims data from North Carolina Medicaid.
Claims were available for all Medicaid recipients in the state and included
all prescription claims submitted to North Carolina Medicaid. Prescriptions
not filled or processed were not available. All variables from the prescription
claim file were entered into a plain text file, grouped by calendar year between
1992 and 1998, and entered into STATA 6.0 (College Station, Tex) statistical
software for data management and analysis.
Prescription claims of interest were searched by National Drug Classification
code using a query of all stimulants and SSRIs listed in the 1999 Physician's Desk Reference, 53rd edition.24
All dosage forms and strengths for each medication were included in our search
for brand-name medications and generic equivalents (when applicable). An injectable
stimulant, doxapram hydrochloride, was excluded. The list of medications included
in our search were as follows: for SSRIs: Luvox (fluvoxamine), Paxil (paroxetine),
Prozac (fluoxetine), and Zoloft (sertraline), and for stimulants: Adderall,
Cylert (pemoline), Desoxyn (methamphetamine hydrochloride), Dexedrine (dextro-amphetamine
sulfate), Dextrostat (d-amphetamine), Ritalin (methylphenidate hydrochloride),
and Ritalin sustained release (methylphenidate hydrochloride sustained release).
The National Drug Classification code provided the medication name, dosage
form, and medication strength. During the period of study, there were no known
statewide formularies or restrictions on any of the medications. Fluoxetine
(Prozac) and most of the stimulants were available before 1992 at the beginning
of the study period. Sertraline (Zoloft), paroxetine (Paxil), and fluvoxamine
(Luvox) were available in the United States beginning in 1992, 1993, and 1994,
respectively, with approval and indication for adult patients.
The Medicaid prescription claims included variables on patient age,
sex, self-reported racial group, county of residence, pharmacy type and location,
prescription quantity, and date the prescription was filled for all patients.
Unique identification numbers were used to link multiple drug claims to each
individual during a calendar year. Patient names were deleted and individuals
were not identified. Denominator information on the North Carolina Medicaid
population age, sex, and race was obtained from Health Care Financing Administration
state Medicaid recipient reports (Health Care Financing Administration–2082
Reports) for fiscal years 1992 through 1998. Health Care Financing Administration
recipient figures on age, sex, and racial demographics were reported by age
category subgroups of 1 to 5 years and 6 to 14 years; thus, subanalyses of
sex and racial groups focused on preschool children (age 1-5 years) and school-aged
children (6-14 years).
Results were compiled for each prescription claim, class of medication
(SSRI or stimulant), and combination of both an SSRI and a stimulant during
each year. Then, the same figures were calculated by number of Medicaid patients
receiving a prescription during the year to account for repeat claims filled
for patients with multiple refills or duplicate medication claims within a
year.
Patients were described as combination prescription recipients if they
received both a stimulant and an SSRI during the same calendar year. Given
the limits of the claims data, and uncertainty about compliance and duration
that patients actually took these medications in combination, we used this
method to approximate the number of combination prescriptions. A review of
1998 data showed that for stimulants and SSRI prescriptions filled during
the same year, 83% of prescription claims for a stimulant and an SSRI were
filled during the same month, and more than 90% were filled within 1 month.
Thus, we believe that this measure is a close approximation of children who
were concurrently taking stimulants and SSRIs.
RESULTS
OVERALL TRENDS AND PRESCRIPTION PREVALENCE
The overall number of stimulant and SSRI prescriptions filled by children
in the North Carolina Medicaid Program increased dramatically from 1992 to
1998. In 1992, 24 584 stimulant prescription claims were filled for 6407
children aged 1 to 19 years. During 1998, these figures increased to 135 057
stimulant prescription claims for 27 951 children. For the SSRIs, 1326
SSRI prescription claims were filled for 510 children aged 1 to 19 years in
1992. Prescriptions increased to 25 392 SSRI claims for 6984 children
in 1998.
Some of the increase in the overall number of prescription claims and
patients receiving medications was caused by expansion of the Medicaid population
from 342 333 children in 1992 to 581 088 in 1998. However, significant
increases were also noted when claims were analyzed as annual prevalence of
prescriptions using the number of Medicaid recipients in a specific age group
as a denominator. Table 1 lists
the prescription prevalence per number of preschool children (1-5 years of
age) and school-aged children (6-14 years of age) who were Medicaid recipients
during 1992 through 1998. Stimulant prevalence doubled from 1992 to 1998,
and SSRI prevalence increased even more during the 7-year period of study.
In the school-aged group, 1998 prescription prevalence leveled off at 9.5%
for stimulants and 1.5% for SSRIs. Stimulant prescription prevalence in preschool
children plateaued at 1.3%, and SSRIs continued a slow rise to 0.1% in 1998.
Although an increased proportion of preschoolers received medications, this
subset of patients still represents a relatively small percentage of all children
who received stimulants and SSRIs. Preschool children (aged 1-5 years) accounted
for only 7.1% of all stimulant prescription claims and 2.2% of all SSRI claims
filled by children aged 1 to 19 years.
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Table 1. Prescription Trends in Preschool and School-aged Children
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DEMOGRAPHIC TRENDS AMONG MEDICAID PATIENTS RECEIVING STIMULANTS AND
SSRIs
The mean age for all children in the Medicaid population who were prescribed
SSRIs decreased from 14.9 years in 1992 to 13.1 years in 1998. However, for
stimulants the mean age actually increased slightly from 8.5 to 9.1 years
during the period of study.
In addition to changes in age, sex differences were also noted. Our
results were consistent with previous reports of a male predominance of attention-deficit/hyperactivity
disorder diagnosis and treatment.25, 26
During the most recent year, 1998, the male-female ratio of stimulant recipients
was 3.2:1. This ratio decreased from a male-female ratio of 4.2:1 in 1992.
Selective serotonin reuptake inhibitors were prescribed to female patients
more commonly in 1992 (female-male ratio, 1.8:1), but in 1998, SSRI prescriptions
were equal with respect to sex (1:1 ratio).
Demographic differences by reported race of prescription recipients
were also noted. In 1992, 56.4% of children who were prescribed stimulants
and 74.9% of children who were prescribed SSRIs were white. The racial differences
narrowed between 1992 and 1998, yet white children still constituted the majority
of patients prescribed stimulants (50.6%) and SSRIs (65.9%) in 1998. However,
white children did not make up a majority of Medicaid children—in 1998,
the North Carolina Medicaid pediatric population was reported as 39.7% white,
48.3% black, and 12.0% other racial groups. Asian, Hispanic, American Indian,
and other racial groups reported by Medicaid also seemed to be less likely
to receive stimulants and SSRIs, although the number of patients in this group
was small; thus, statistical comparisons were not made with white patients.
Prescription prevalence as a percentage of preschool and school-aged
Medicaid children in 1998 are shown in Table 2 by sex and racial groups. White school-aged males had the
highest stimulant prescription prevalence of more than 18% and the highest
SSRI prevalence of nearly 3%. Stimulant and SSRI prevalence for white male
patients were consistently higher than prevalence of other racial and sex
groups for preschool and school-aged children (P<.01).
Racial differences in prescription prevalence were even greater for SSRIs
than stimulants, with a 2- to 3-fold higher annual SSRI prevalence for white
Medicaid patients compared with black children of the same age groups (P<.001).
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Table 2. 1998 Prescription Prevalence in Medicaid Preschool (Aged 1-5
Years) and School-aged (Aged 6-14 Years) Children by Racial Group and Sex*
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COMBINATION PRESCRIPTIONS
In addition to increases in the individual medications, greater prescription
of stimulants and SSRIs in combination occurred during the study period. The
number of patients prescribed both types of psychotropic medications during
the same year increased steadily. Since SSRIs had been recently introduced
at the beginning of the study period, in 1992, only 32 children received both
stimulants and SSRIs during this year, yet by 1998, 2102 pediatric patients
were prescribed both types of medication. The combination of stimulants and
SSRIs is still relatively rare among all Medicaid children, with an annual
combination prescription prevalence among school-aged children of 0.7%. However,
among the 6984 children who received an SSRI in 1998, 30.1% also received
a stimulant.
COMMENT
Annual prescription prevalence of stimulants, SSRIs, and combination
prescriptions in our study increased significantly from 1992 to 1998 in the
North Carolina Medicaid population of children aged 1 to 19 years. Increases
were noted for all measures: number of prescriptions filled, number of patients
prescribed a medication, and the percentage of preschool and school-aged children
prescribed a medication annually. Our study results are consistent with other
reports documenting the trend of increased psychotropic prescriptions for
children and adolescents during the 1990s. However, stimulant prevalence of
almost 10% in the 1998 school-aged group is greater than the reported attention-deficit/hyperactivity
disorder prevalence from many community samples and other studies of stimulant
prevalence.2, 3, 4, 5, 6, 7, 26, 27, 28, 29
In addition, subgroups such as white school-aged males had even higher stimulant
prevalence of more than 18%. Selective serotonin reuptake inhibitors are prescribed
less frequently than stimulants, yet this class of antidepressants has also
become an important part of therapy for many children. In addition, there
are some new and unique significant findings to note.
First, the trend of increased stimulant prescriptions and SSRI prescriptions
continued through 1998. Despite controversy over off-label usage, questions
of efficacy in the pediatric population, and safety concerns for young children,
prescriptions have continued to climb for both stimulants and SSRIs in all
age groups. Stimulant increases were dramatic: the number of prescriptions
and patients increased by nearly 4-fold during the study period of 1992 through
1998. Some of this increase was because of an expansion in the number of children
and adolescents receiving Medicaid. However, even after considering changes
in the number of Medicaid recipients, increases were dramatic, with a doubling
of the percentages of Medicaid preschoolers and school-aged children receiving
stimulants between 1992 and 1998. It is somewhat more difficult to interpret
increases in SSRI use, since the class of medications was just introduced
in 1988, and the other 3 SSRIs were launched during the period of study. However,
during the last 5 years of the study period, the percentages of preschool
and school-aged children receiving SSRIs have more than doubled.
Many articles, and even a recent White House conference, have raised
concerns about increases in prescription rates, and potential overuse, inappropriate
prescriber practices, and substitution for counseling or comprehensive therapy.29, 30 While our findings are provocative,
we cannot speculate from our data what factors are driving prescription increases.
Potential positive influences of increased recognition and treatment of previously
unrecognized mental disorders, improvements in access to psychiatric care,
or increased education about the proper use of these medications must be considered
along with concerns of harmful effects and negative associations with expansion
of prescription utilization. Recent clinical trials have shown the potential
promise and benefit for these drugs in selected pediatric patients.31, 32, 33 While we must be
judicious in the application of these psychotropic medications, we cannot
present an alarmist view that equates all increases in prescriptions with
negative consequences. Our study is a first step to describe some of the issues
surrounding care for complex disorders. Future studies must describe utilization
patterns, diagnostic appropriateness, severity of illness adjustments, and
ultimately describe patient outcomes in terms of adverse events and benefits
from stimulants and SSRIs.
Second, important demographic trends were observed. Although most stimulants
and SSRIs were prescribed for older children and adolescents, more young patients
and even preschoolers received these medications. Males continued to receive
stimulants more commonly than females, but the sex gap has narrowed, and SSRI
prevalence by sex was approximately equal between males and females in 1998.
Finally, we demonstrated differences in stimulant and SSRI prescription prevalence
for whites and other racial groups in our study. Our results confirm data
from the Maryland Medicaid pediatric population,26, 27
and show that in addition to demographic differences in stimulant prescriptions,
SSRI prescriptions have even greater differences between whites and black
Medicaid children. The results must be viewed with caution as racial misclassifications,
cultural beliefs of mental illness, access to care, and differential acceptance
of psychotropics may vary among racial groups. However, our results demand
additional study to understand disparities between stimulant and SSRI prescription
patterns for white and nonwhite patients.
The third major finding is the growing trend of combination pharmacotherapy
with stimulants and SSRIs. Concerns of individual medication safety in children,
which are still largely unknown and unexplored, are magnified when combinations
of medicines are prescribed for children. While this trend may reflect a greater
attention to comorbidity with attention-deficit/hyperactivity disorder, depression,
or other mental disorders, this practice bears additional scrutiny. Clinical
trials and open-label trials have provided some information on stimulant and
SSRI use as single agents in select populations of children; however, there
are minimal to no data to describe the risks and potential benefits of polypharmacy
with these medications. This practice may prove to be safe and effective,
yet these patients are often excluded from clinical trials and studies. Combination
pharmacotherapy and patients with coexisting conditions must become part of
the research agenda.
Our study has several important limitations that must be considered.
First, our results describe prescription trends in a single state Medicaid
population. Although Medicaid patients represent a significant percentage
of children in the state, our results may not generalize to other states or
patient populations. In addition to generalizability, the Medicaid population
faces several other challenges in access and changing needs that could affect
prescriber practices. Changing characteristics and effects of enrollment and
disenrollment may also affect prescription trends. It is possible that the
expansion of Medicaid preferentially enrolled underinsured patients without
previous drug benefits, adolescents with higher prevalence of mental health
needs, or more severely ill patients with greater mental health care and prescription
needs. Some of the increases in prescription figures may be because of a longer
chronicity of therapy or changes in severity and recurrence of mental disorders
in our study population. Differences in reporting of the number of Medicaid
children during different periods and claim dates may contribute to variations
in the denominator population. Other studies on the Medicaid data have reported
prescription prevalences that exceed estimates from other samples and patient
populations.34 Thus, our results may overestimate
true prescription prevalence.
Additional studies are needed to link Medicaid prescription claims with
utilization of other services, concurrent treatment, diagnosis and disease
severity, recurrence, physician characteristics, and patient outcomes data.
It remains to be seen how increases in prescriptions reflect other processes
and quality of care. In fact, one hypothesis that must be tested is whether
higher prescription prevalences may actually reflect increased access to care,
recognition of mental health needs, and engagement in long-term treatment.
We have demonstrated the clear need for this type of research in the Medicaid
population where psychotropic prescriptions for youth affect a large percentage
of the population.
CONCLUSIONS
We have shown that stimulant prevalence along with SSRIs and combination
prescriptions for children and adolescents have increased between 1992 and
1998. Stimulants are prescribed more commonly for children, yet SSRIs and
other new psychotropics must also be considered and studied. The next step
and challenge of health services research is to consider the effects of psychotropic
prescription practices on utilization of other services (inpatient hospitalizations,
counseling, and medical services), medical and mental health expenditures,
and outcomes for children and their families. Differences in treatment by
age, sex, and race must be specifically addressed in future research. If changes
in practice patterns and drug use are found to be associated with variations
in quality of care and patient outcomes, interventions must be designed to
address inappropriate prescription practices in both directions—overprescription
and underutilization of other treatment and services.
AUTHOR INFORMATION
Accepted for publication December 29, 2000.
This work was supported by the Robert Wood Johnson Clinical Scholars
Program.
We thank the State Center for Health Statistics, North Carolina
Department of Health and Human Services, Raleigh, for providing data access
and other assistance.
From the Division of General Pediatrics,
Department of Pediatrics, University of Michigan, Ann Arbor
(Dr Rushton); and the State Center for Health Statistics, North Carolina
Department of Health and Human Services, Raleigh (Dr
Whitmire).
Corresponding author: Jerry L. Rushton, MD, MPH, Department of Pediatrics,
University of Michigan, 300 North Ingalls Bldg, Room 6D05, Ann Arbor, MI 48109-0456
(e-mail: jrushton{at}umich.edu).
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Arch. Dis. Child. 2004;89:1098-1102.
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Age Effects on Antidepressant-Induced Manic Conversion
Martin et al.
Arch Pediatr Adolesc Med 2004;158:773-780.
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Use of Practice Guidelines in the Primary Care of Children With Attention-Deficit/Hyperactivity Disorder
Rushton et al.
Pediatrics 2004;114:e23-e28.
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National trends in concomitant psychotropic medication with stimulants in pediatric visits: Practice versus knowledge
Bhatara et al.
J Atten Disord 2004;7:217-226.
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Quality of Care for Medicaid-Covered Youth Treated With Antidepressant Therapy
Richardson et al.
Arch Gen Psychiatry 2004;61:475-480.
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Brief Reports: Use of Psychotropic Medications by Youths With Psychiatric Diagnoses in the U.S. Mental Health System
Warner et al.
Psychiatr. Serv. 2004;55:309-311.
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Outpatient Treatment of Child and Adolescent Depression in the United States
Olfson et al.
Arch Gen Psychiatry 2003;60:1236-1242.
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Relationship Between Antidepressant Medication Treatment and Suicide in Adolescents
Olfson et al.
Arch Gen Psychiatry 2003;60:978-982.
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A Longitudinal Evaluation of Adolescent Depression and Adult Obesity
Richardson et al.
Arch Pediatr Adolesc Med 2003;157:739-745.
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National Trends in the Treatment of Attention Deficit Hyperactivity Disorder
Olfson et al.
Am. J. Psychiatry 2003;160:1071-1077.
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Concomitant Psychotropic Medication for Youths
Safer et al.
Am. J. Psychiatry 2003;160:438-449.
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Prescribing of Psychotropic Medications for Children by Australian Pediatricians and Child Psychiatrists
Efron et al.
Pediatrics 2003;111:372-375.
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Psychotropic Practice Patterns for Youth: A 10-Year Perspective
Zito et al.
Arch Pediatr Adolesc Med 2003;157:17-25.
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Consultation With the Specialist: The Central Serotonin Syndrome: Paradigm for Psychotherapeutic Misadventure
Arnold
Pediatr. Rev. 2002;23:427-432.
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National Trends in the Use of Outpatient Psychotherapy
Olfson et al.
Am. J. Psychiatry 2002;159:1914-1920.
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Rising Prevalence of Antidepressants Among US Youths
Zito et al.
Pediatrics 2002;109:721-727.
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Psychotropic Medication Use in a Population of Children Who Have Attention-Deficit/Hyperactivity Disorder
Guevara et al.
Pediatrics 2002;109:733-739.
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How Common Is Attention-Deficit/Hyperactivity Disorder?: Incidence in a Population-Based Birth Cohort in Rochester, Minn
Barbaresi et al.
Arch Pediatr Adolesc Med 2002;156:217-224.
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Increased Psychotropic Medication Use: Are We Improving Mental Health Care or Drugging Our Kids?
Wolraich
Arch Pediatr Adolesc Med 2001;155:545-545.
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