Trends in the Prescribing of Psychotropic Medications to Preschoolers Julie Magno Zito, PhD Context Recent reports on the use of psychotropic medications for preschool-aged
children with behavioral and emotional disorders warrant further examination of trendsin the type and extent of drug therapy and sociodemographic correlates. Objectives To determine the prevalence of psychotropic medication use in preschool-
aged youths and to show utilization trends across a 5-year span. Design Ambulatory care prescription records from 2 state Medicaid programs and a
salaried group-model health maintenance organization (HMO) were used to performa population-based analysis of three 1-year cross-sectional data sets (for the years 1991,
THEPREVALENCEOFPSYCHO- 1993,and1995). Setting and Participants From 1991 to 1995, the number of enrollees aged 2 through
4 years in a Midwestern state Medicaid (MWM) program ranged from 146 369 to
158 060; in a mid-Atlantic state Medicaid (MAM) program, from 34 842 to 54 237;
orders has significantly increased in the
and in an HMO setting in the Northwest, from 19 107 to 19 322. Main Outcome Measures Total, age-specific, and gender-specific utilization preva-
cades, particularly in the last 15 years.
lences per 1000 enrollees for 3 major psychotropic drug classes (stimulants, antide-
pressants, and neuroleptics) and 2 leading psychotherapeutic medications (methyl-
phenidate and clonidine); rates of increased use of these drugs from 1991 to 1995,
Results The 1995 rank order of total prevalence in preschoolers (per 1000) in the MWM
program was: stimulants (12.3), 90% of which represents methylphenidate (11.1); anti-
depressants (3.2); clonidine (2.3); and neuroleptics (0.9). A similar rank order was observedfor the MAM program, while the HMO had nearly 3 times more clonidine than antide-
pressant use (1.9 vs 0.7). Sizable increases in prevalence were noted between 1991 and
1995 across the 3 sites for clonidine, stimulants, and antidepressants, while neuroleptic use
increased only slightly. Methylphenidate prevalence in 2- through 4-year-olds increased
at each site: MWM, 3-fold; MAM, 1.7-fold; and HMO, 3.1-fold. Decreases occurred in
the relative proportions of previously dominant psychotherapeutic agents in the stimulant
and antidepressant classes, while increases occurred for newer, less established agents. Conclusions In all 3 data sources, psychotropic medications prescribed for pre-
schoolers increased dramatically between 1991 and 1995. The predominance of medi-
cations with off-label (unlabeled) indications calls for prospective community-based,
sis (6-year-olds and older); and am-phetamines for ADHD in those 3 years
Author Affiliations: School of Pharmacy (Drs Zito,
dosReis, and Mr Gardner) and School of Medicine (Dr
Zito), University of Maryland, and School of Medi-cine, Johns Hopkins University (Dr Safer), Baltimore,
lates to off-label (unlabeled) use, ie, for
Md; and Center for Health Research, Kaiser Perma-
nente, Portland, Ore (Drs Boles and Lynch). Corresponding Author and Reprints: Julie Mango Zito, PhD, University of Maryland, 100 Greene St, Room 5-13, For editorial comment see p 1059.
Baltimore, MD 21201 (e-mail: [email protected]). 2000 American Medical Association. All rights reserved.
JAMA, February 23, 2000—Vol 283, No. 8 1025 Study Measures
stantially since the early 1990s. All the
medication per 1000 enrolled youths.
tion by the institutional review board–
Total Psychotropic Medication
were grouped into 4 age strata (aged 2-4,
Prevalence
years. We were unable to investigate psy-
corded in a 2-digit field. Thus, “95”
roleptics (0.9) (TABLE). Within classes, Data Sources
in a mid-Atlantic state. The third set of
school-aged children by year of age. Psychotropic Medications
tinuous enrollees for each study year. Time Trends in Psychotropic Medication Prevalence Across a 5-Year Span
cording to general statistical profiles of
1026 JAMA, February 23, 2000—Vol 283, No. 8 2000 American Medical Association. All rights reserved.
fold), and antidepressants (2.2-fold). By
Changes in Drug Utilization and Off-Label Use
crease substantially during this time.
were similar in all 3 sites, with minor de-
viations for neuroleptics and antidepres-
matic when the base prevalence was low. Gender-Specific Methylphenidate Medication Prevalence
HMO (FIGURE 2). Thus, antidepres- Age-Specific Methylphenidate Medication Prevalence
(FIGURE 1). By comparison, children 2
program (4:1 in 1991 to 3:1 in 1995).
5- through 14-year-old counterparts. Table. Annual Prevalence Rate per 1000 2- Through 4-Year-Old Children for Selected Psychotropic Medications in 3 Health Care Sites (1991, 1993, 1995)* MWM (n = 151 675) MAM (n = 51 970) HMO (n = 19 322) Prevalence Prevalence Prevalence (95% Confidence Interval) (95% Confidence Interval) (95% Confidence Interval) Increase, Increase, Increase, 1991-1995 1991-1995 1991-1995
*Prevalence (confidence interval) gives the upper and lower limits of the mean prevalence estimate with 95% probability of accuracy. Confidence intervals were truncated at 0.
MWM indicates a Midwestern state Medicaid program; MAM, a mid-Atlantic state Medicaid program; and HMO, health maintenance organization. N represents the number ofenrollees aged 2 through 4 years in 1995 for the health care site. 2000 American Medical Association. All rights reserved.
JAMA, February 23, 2000—Vol 283, No. 8 1027
clinical studies to evaluate the efficacy
largely uncharted,17,18 and its increased
with questions of safety16,21 and has been
stimulants across the 3 time periods.
tions; age- and gender-specific data; and
older youths to preschoolers is often not
sored data do not create artifactual find-
schoolers’ developmental immaturity. Prevalence Findings
lant and clonidine use is consistent with
efit of rigorous data to support it as a safe
Figure 1. Methylphenidate Prevalence per 1000 Enrollees Across a 5-Year Span (1991-1995)
Trends in age-specific methylphenidate prevalence per 1000 enrollees by age for the Midwestern state Medicaid population. Left, Enrollees aged 2 through 19 years. Right, Enrollees aged 2 through 4 years. 1028 JAMA, February 23, 2000—Vol 283, No. 8 2000 American Medical Association. All rights reserved.
derlie families’ decisions to accept or re-
zling. It is also likely that some use of
prevalence rates, collectively, were sub-
tions in this analysis, thus limiting in-
presence of less severely disabled youths
plain a large part of the differences, but
ber of variables to describe the clinical
tors need to be considered as well. Also,
patterns in the usual practice settings.
scribing the usual practice setting with-
out the artificiality and the interference
Age- and Gender-Specific
sicians’ decisions about medication and
Prevalence Findings
patients’ decisions about treatment. Limitations
The study is limited in several ways.
tices, therapy variations, and treatment.
extends even to the very young. It isnotable that the largest gains in use
Figure 2. Distribution of Antidepressant Subclasses Among Preschoolers in 3 Health Care
dents (15- through 19-year-olds), atrend that has been documented from
Geographic and Health Care System Variations
Disparities in psychotropic medica-tion prevalence data between the 2 state
vocative and suggest numerous hypoth-eses. These include differences be-
eligibility or access to continuing care;
Trends in the percent distribution of antidepressant subclasses among preschoolers in 3 health care sites. MWM
indicates a Midwestern state Medicaid program; MAM, a mid-Atlantic state Medicaid program; HMO, health
maintenance organization; TCA, tricyclic antidepressant; and SSRI, selective serotonin reuptake inhibitor. Theproportions exceed 100% because more than 1 class may have been used in the same individual. 2000 American Medical Association. All rights reserved.
JAMA, February 23, 2000—Vol 283, No. 8 1029
cebo-controlled study. J Child Adolesc Psycho-pharmacol. 1998;8:13-25.
cations, particularly in light of earlier
12. Valentine J, Zubrick S, Sly P. National trends in
the use of stimulant medication for attention deficit
of treatment. While it is reassuring that
hyperactivity disorder. J Paediatr Child Health. 1996;32:223-227. Clinical Research 13. Safer DJ, Zito JM. Pharmacoepidemiology of meth- Recommendations
ylphenidate and other stimulants for the treatment ofADHD. In: Greenhill LL, Osman BB, eds. Ritalin: Theory
Because children’s responses to medica-
of adverse effects on the developing brain
and Practice. 2nd ed. Larchmont, NY: MA Liebert Pub-
tions are not necessarily similar to those
14. Davilla RR, Williams ML, MacDonald JT. Clarifi- cation of policy to address the needs of children with
attention deficit hyperactivity disorders within gen-
eral and/or special education. Memorandum from: USDept of Education. Washington, DC: US Dept of Edu-
cation, Office of Special Education; September 16,
1991. 15. Cantwell DP, Swanson J, Connor DF. Case study: Funding/Support: This study was supported by fund-
adverse response to clonidine. J Am Acad Child Ado-
ing from the National Institute of Mental Health, Ser-
lesc Psychiatry. 1997;36:539-544.
vices Branch (grant R01 MH55259), and the George
16. Swanson JM, Flockhart DA, Udrea D, Cantwell DP, Connor DF, Williams L. Clonidine in the treat-
and Leila Mathers Charitable Foundation, Mount Kisco,NY.
ment of ADHD: questions about safety and efficacy
Previous Presentation: Presented at the American Psy-
[letter]. J Child Adolesc Psychopharmacol. 1995;5:301-304.
chiatric Association Meeting, Washington, DC, May19, 1999. 17. Prince JB, Wilens TE, Biederman J, Spencer TJ, Acknowledgment: Richard E. Johnson, PhD, and Linda
Wozniak JR. Clonidine for sleep disturbances associ-
treatments, diagnosis, severity, and time
Phelps, MA, provided assistance at several stages in
ated with attention-deficit hyperactivity disorder: a sys-
the design or analysis of this study. Medicaid admin-
tematic chart review of 62 cases. J Am Acad Child Ado-
istrators and research analysts gave crucial support to
lesc Psychiatry. 1996;35:599-605. 18. Ahmann PA, Waltonen SJ, Olson KA, Theye FW, Van Erem AJ, LaPlant RJ. Placebo-controlled evalua-
tion of Ritalin side effects. Pediatrics. 1993;91:1101-
REFERENCES
1106. 19. Erickson SJ, Duncan A. Clonidine poisoning—an
satisfaction; reasons for initiation and dis-
1. Safer DJ, Zito JM, Fine EM. Increased methylphe- nidate usage for attention deficit disorder in the 1990s.
emerging problem: epidemiology, clinical features,
Pediatrics. 1996;98(6 pt 1):1084-1088.
management and preventive strategies. J Paediatr2. Zito JM, dosReis S, Safer DJ, Gardner J. Trends in Child Health. 1998;34:280-282. 20. Kappagoda C, Schell DN, Hanson RM, Hutchins
trolled clinical trials are needed for off-
psychotropic prescriptions for youths with Medicaidinsurance from a midwestern state: 1987-1995. Pa-
P. Clonidine overdose in childhood: implications of in-
label indications to evaluate dosages, ef-
per presented at: New Clinical Drug Evaluation Unit
creased prescribing. J Paediatr Child Health. 1998;34:508-512.
ficacy, and safety of single and multiple
Meeting; June 1998; Boca Raton, Fla. 3. Greenhill LL. The use of psychotropic medication 21. Popper CW. Combining methylphenidate and
in preschoolers: indications, safety, and efficacy. Can
clonidine: pharmacologic questions and news re-ports about sudden death. J Child Adolesc Psycho-J Psychiatry. 1998;43:576-581. 4. Minde K. The use of psychotropic medication in
preschoolers: some recent developments. Can J Psy-22. Wilens TE, Spencer TJ, Swanson JM, Connor DF,
Cantwell D. Combining methylphenidate and cloni-
5. Rappley MD, Gardiner JC, Mullan PB, Wang J,
dine: a clinically sound medication option vs. ill-
Alvarez FJ. Psychotropic medications in children
advised. J Am Acad Child Adolesc Psychiatry. 1999;
ages 1 to 3 with ADHD. Paper presented at: Pediat-
38:614-619. 23. Pincus HA, Tanielian TL, Marcus SC, et al. Pre-
ric Academic Societies Meeting (Joint Specialtiesand Themes: Behavioral Pediatrics); May 4, 1998;
scribing trends in psychotropic medications: primary
care, psychiatry, and other medical specialties. JAMA. 6. Pathiyal A, Miwa LJ, Sverdiov LS, Gardner E, Jones
JK. Patterns of methylphenidate use. Paper pre-
24. Foxman B, Valdez RB, Brook RH. Childhood en-
sented at: American Society for Clinical Pharmacol-
uresis: prevalence, perceived impact, and prescribed
ogy and Therapeutics; March 31, 1998; New Or-
treatments. Pediatrics. 1986;77:482-487. 25. Geller B, Reising D, Leonard HL, Riddle MA, Walsh 7. Vitiello B, Jensen PS. Medication development and
BT. Critical review of tricyclic antidepressant use in chil-
testing in children and adolescents: current prob-
dren and adolescents. J Am Acad Child Adolesc Psy-chiatry. 1999;38:513-516.
lems, future directions. Arch Gen Psychiatry. 1997;54:871-876. 26. Traversa G, Spila-Alegiani S, Arpino C, Ferrara M. 8. Grinfeld MJ. Psychoactive medications and kids: new
Prescription of neuroleptics for children and adults in Italy.
initiatives launched. Psychiatric Times. 1998;15:69. J Child Adolesc Psychopharmacol. 1998;8:175-180. 9. Zito JM, Safer DJ, Riddle MA, Johnson RE, Speedie 27. Perrin JM, Kuhlthau K, McLaughlin TJ, Ettner SL,
SM, Fox M. Prevalence variations in psychotropic treat-
Gortmaker SL. Changing patterns of conditions among
ment of children. J Child Adolesc Psychopharmacol.
children receiving Supplemental Security Income dis-
ability benefits. Arch Pediatr Adolesc Med. 1999;153:
10. Jensen PS, Vitiello B, Leonard H, Laughren TP.
Child and adolescent psychopharmacology: expand-
28. Hoagwood K, Jensen PS, Petti T, Burns BJ. Out-
ing the research base. Psychopharmacol Bull. 1994;
comes of mental health care for children and adoles-
jor social stressors, will not be unfairly
cents, I: a comprehensive conceptual model. J Am Acad11. Firestone P, Musten LM, Pisterman S, Mercer J, Child Adolesc Psychiatry. 1996;35:1055-1063.
Bennett S. Short-term side effects of stimulant medi-
29. Vitiello B. Pediatric psychopharmacology and the
cation are increased in preschool children with atten-
interaction between drugs and the developing brain.
tion-deficit/hyperactivity disorder: a double-blind pla-
Can J Psychiatry. 1998;43:582-584. 1030 JAMA, February 23, 2000—Vol 283, No. 8 2000 American Medical Association. All rights reserved.
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