Microsoft word - article 03-0
Trends in the Prescribing of Psychotropic Medications to
JAMA, Vol. 283 No. 8, February 23, 2000, pp. 1025-1030.
Julie Magno Zito, PhD; Daniel J. Safer, MD; Susan dosReis, PhD; James F.
Gardner, ScM; Myde Boles, PhD; Frances Lynch, PhD
Context:Recent reports on the use of psychotropic medications for preschool-agedchildren with behavioral and emotional disorders warrant further examination oftrends in the type and extent of drug therapy and sociodemographic correlates.
Objectives:To determine the prevalence of psychotropic medication use in preschool-agedyouths and to show utilization trends across a 5-year span.
Setting and Participants:From 1991 to 1995, the number of enrollees aged 2 through 4 years in aMidwestern 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; and inan HMO setting in the Northwest, from 19,107 to 19,322.
Main Outcome Measures:
Total, age-specific, and gender-specific utilization prevalences per 1000
enrollees for 3 major psychotropic drug classes (stimulants, antidepressants,
and neuroleptics) and 2 leading psychotherapeutic medications
and clonidine [CATAPRES]
); rates of increased
use of these drugs from 1991 to 1995, compared across the 3 sites.
The 1995 rank order of total prevalence in preschoolers (per 1000) in the MWM
program was: stimulants (12.3), 90% of which represents methylphenidate[RITALIN]
(11.1); antidepressants (3.2); clonidine [CATAPRES]
neuroleptics (0.9). A similar rank order was observed for the MAM program,
while the HMO had nearly 3 times more clonidine [CATAPRES]
antidepressant use (1.9 vs 0.7). Sizable increases in prevalence were noted
between 1991 and 1995 across the 3 sites for clonidine [CATAPRES]
stimulants, and antidepressants, while neuroleptic use increased only slightly.
prevalence in 2 through 4-year-olds increased at
each site: MWM, 3-fold; MAM, 1.7-fold; and HMO, 3.1-fold.
Conclusions:In all 3 data sources, psychotropic medications prescribed for preschoolersincreased dramatically between 1991 and 1995. The predominance ofmedications with off-label (unlabeled) indications calls for prospectivecommunity-based, multidimensional outcome studies.
“The prevalence of psychotropic medication treatment for children andadolescents with emotional and behavioral disorders has significantly increasedin the United States during the last few decades, particularly in the last 15years.”
“The 5 through 14-year-old age group has experienced a great increase instimulant treatment for attention-deficit/hyperactivity disorder (ADHD), and the15 through 19-year-old age group has had sizable increases in the use ofantidepressant medications.”
The prevalence of psychotropic medication treatment for children younger than5 years old has not received much professional attention.
The concern for children younger than 5 years old is because of the off-label(unlabeled) use of these medications. Off-label use means use for “treatmentindications with little or no proven efficacy.”
A psychiatric newsletter reported that 3000 prescriptions for fluoxetine
were written for children aged younger than 1 year in
In 1998 pediatric researchers noted that 57% of 223 Michigan Medicaid
enrollees aged younger than 4 years with a diagnosis of ADHD received at least
1 psychotropic medication to treat this condition. Treatment with
and clonidine [CATAPRES]
were most common.
In this article, the authors used 3 large, computerized data sources to estimatetotal, age-specific, and gender-specific psychotropic medicationprevalence for 2 through 4-year-olds; and to show utilization trends in the5-year span from 1991-1995.
Psychotropic medication prevalence trends were assessed for age-specificprevalence. Children were grouped into 4 age strata: 2-4, 5-9, 10-14, and 15-19 years. Data analyses focused on children aged 2 through 4 years.
The authors were unable to investigate psychotropic medication use in infants 1year old or younger because their computers could not distinguish those 1 yearold and younger from 100- and 101-year-olds.
Three psychotropic medication classes were examined:(1)
, other stimulants)
(selective serotonin reuptake inhibitors [SSRIs], [Prozac, Paxil]
tricyclic antidepressants [TCAs], and other antidepressants)
There is frequent use of stimulants and antidepressants and there is publichealth significance to the use of neuroleptics in the very young.
Two specific medications (methylphenidate [RITALIN]
) were examined because their use alone or as a combined
treatment has increased substantially since the early 1990s.
RESULTSTotal Psychotropic Medication Prevalence
Stimulants were the leading treatment among those 2 through 4 years old,
followed by antidepressants, clonidine [CATAPRES]
, and neuroleptics.
prevalence represented 90% of the stimulant
TCA prevalence led the antidepressant class.
The HMO assessed had nearly 3 times more clonidine [CATAPRES]
Time Trends in Psychotropic Medication Prevalence Across a 5-Year Span
“The rate of psychotropic medication prescribed for preschoolers in the MWM
program increased substantially from 1991-1995. The increase was greatest for
(28.2-fold), stimulants (3.0-fold), and antidepressants
Age-Specific Methylphenidate [RITALIN]
use was most prominent for those aged 5 through
“The largest methylphenidate [RITALIN]
increase (311%) was among 15
through 19-year-olds, whereas the 2 through 4-year-olds, like the 5 through
14-year-olds, had a smaller but still substantial increase (169% to 176%).”
Gender-Specific Methylphenidate [RITALIN]
“There was a greater proportional increase in preschool-aged girls receiving
from 1991 through 1995.”
Changes in Drug Utilization and Off-Label Use
“The use of SSRI antidepressants increased dramatically at the Medicaid sites,although by 1995 these drugs comprised only a small proportion ofantidepressants used in the HMO.”
“Antidepressant use increased, particularly through off-label use, in thepreschool-aged group.”
“Several prominent trends characterized the use of psychotropic medications inpreschoolers during the early to mid 1990s.”
“Overall, there were large increases for all study medications (except theneuroleptics).”
“These findings are remarkable in light of the limited knowledge base thatunderlies psychotropic medication use in very young children.”
“Controlled clinical studies to evaluate the efficacy and safety of psychotropicmedications for preschoolers are rare.”
“Efficacy data are essentially lacking for clonidine [CATAPRES]
and the SSRIs[Prozac, Paxil]
and methylphenidate's [RITALIN]
adverse effects for
preschool children are more pronounced than for older youths.”
“The vast majority of psychotropic medications prescribed for preschoolers arebeing used off-label.”
“Stimulant treatment in preschoolers increased approximately 3 fold during theearly 1990s.”
This pattern of increased use is consistent with an ADHD diagnosis.
Hypothesized reasons for the overall increased stimulant use include:(1) a larger pool of eligible youths because of expanded diagnostic criteria forADHD since 1980.
(2) more girls being treated for ADHD.
(3) greater acceptance of biological treatments for a behavioral disorder.
had the most dramatic increases of stimulant use. This
is particularly notable because “its increased prescribing is occurring without
the benefit of rigorous data to support it as a safe and effective treatment for
“Cardiovascular adverse effects including bradycardia, atrioventricular block,
and syncope with exercise have been reported in children treated with clonidine[CATAPRES]
in combination with other medications for the treatment of ADHD
and its comorbidities.”
Problems with abrupt withdrawal from clonidine [CATAPRES]
noradrenergic overdrive. Clonidine [CATAPRES]
use to “combat the insomnia
associated either with ADHD itself or secondary to the stimulant treatment of
ADHD is new and largely uncharted, and its increased use for ADHD since 1991
helps explain the increased clonidine [CATAPRES]
poisonings in children
taking either their own medications or that of siblings.”
The combined use of clonidine [CATAPRES]
and methylphenidate [RITALIN]
has been associated with questions of safety.
“Antidepressants were the second most commonly prescribed psychotropicclass of drugs for preschoolers, and their use increased substantially from1991-1995.”
Tricyclic antidepressants still represent the bulk of early childhoodantidepressant use.
However, the recent decrease in use of TCAs is largely explained by the recent
increase in use of SSRIs [Prozac, Paxil]
for both older youths and adults.
Age- and Gender-Specific Prevalence Findings
“Preschoolers' use of methylphenidate [RITALIN]
showed increases similar to
those of 5 through 14-year-olds, suggesting that the expanded use of this
medication for attentional disorders in US youths extends even to the very
“It is notable that the largest gains in use occurred among high school–agedstudents, 15 through 19-year-olds.”
“Notable is the finding that the HMO prevalence rates, collectively, weresubstantially lower than those of the Medicaid programs.”
The authors imply that the reason for greater psychotropic medication
prevalence in Medicaid program populations as compared to HMO populations is
because Medicaid coverage pays for these medications with an ADHD diagnosis.[This suggests that our government is partly to blame for the problem
of increasing psychotropic medication use in our children. Apparently,
if the government, we the people, will pay for these drugs, medical
doctors will prescribe them.]
“Because children's responses to medications are not necessarily similar tothose of adults, systematic and careful outcome research specifically needs tobe done for them.”
“Unresolved questions involve the long-term safety of psychotropicmedications, particularly in light of earlier ages of initiation and longerdurations of treatment.”
The possibility of adverse effects on the developing brain cannot be ruled out.
Subtle changes to the developing personality may occur as a result of apsychotropic drug's impact on brain neurotransmitters.
THIS ARTICLE WAS FOLLOWED BY THE FOLLOWING EDITORIAL:
Psychotropic Drug Use in Very Young Children
JAMA, Vol. 283 No. 8, February 23, 2000.
The study by Zito and colleagues in this issue of THE JOURNAL on the use ofpsychotropic medications in very young children suggests that 1% to 1.5% ofall children 2 to 4 years old are receiving stimulants, antidepressants, orantipsychotic medications.
The “prevalence of neuropsychopharmacologic interventions in this age groupincreased substantially during the last decade.”
Several other recent studies “provide additional evidence that the prescriptionof psychotropic drugs to very young children has increased during the lastdecade.”
One study shows a 3-fold increase in methylphenidate [RITALIN]
in Canada and a 10-fold increase in the prescription of selective serotonin
reuptake inhibitors [Prozac, Paxil]
in the United States for children 5 years
old and younger between 1993 and 1997.
“It should be emphasized that most of the drugs prescribed involve off-labeluse because efficacy of psychotropic drugs has not been demonstrated in veryyoung children.”
In fact, methylphenidate [RITALIN]
, the most commonly prescribed drug in
these studies, “carries a warning against its use in children younger than 6
“Furthermore, the validity and reliability of the diagnoses of attention-deficit/hyperactivity disorder, mood disorders, and schizophrenia in very youngchildren have not been demonstrated.”
This author surveyed the editorial board (48 physicians) of the
Journal of Child and Adolescent Psychopharmacology by facsimile about their
prescribing of stimulants, clonidine [CATAPRES]
, antidepressants, and
antipsychotics for 2- to 4-year-old children. Most responded either no use or
very rare prescribing of these medications in this age group, and these are
expert clinicians and clinical researchers who are likely to treat the most
difficult cases. [This suggests that other, less knowledgeable physicians,
are way over prescribing these medications.]
There is virtually no clinical research on the consequences of pharmacologictreatment of behavioral disturbances of very young children.
“Early childhood is a time of tremendous change for the human brain. Visualprocessing, language, and motor skills are acquired during this sensitive period.
The cortical synaptic density reaches its maximum at the age of 3 years and issubstantially modified by pruning during the next 7 years. At the same time,the cerebral metabolic rate peaks between 3 and 4 years of age.”
“Studies in experimental animals indicate that the aminergic systems that arethe target of action of these psychotropic medications play an important role inneurogenesis, neuron migration, axonal outgrowth, and synaptogenesis.”
“Perinatal treatment of rats with an antipsychotic drug results in a long-standing abnormality in dopamine receptor function and altered levels ofdopamine and norepinephrine in adulthood. Thus, it would seem prudent tocarry out much more extensive studies to determine the long-termconsequences of the use of psychotropic drugs at this early stage of childhood.”
“Given that there is no empirical evidence to support psychotropic drugtreatment in very young children and that there are valid concerns that suchtreatment could have deleterious effects on the developing brain, the reasonsfor these troubling changes in practice need to be identified.”
“Many state Medicaid programs now provide quite limited reimbursement forthe evaluation of behavioral disorders in children and preclude more than 1type of clinical evaluator per day. Thus, the multidisciplinary clinics of the pastthat brought together pediatric, psychiatric, behavioral, and family dynamicexpertise for difficult cases have largely ceased to exist.”
Consequently, “it appears that behaviorally disturbed children are nowincreasingly subjected to quick and inexpensive pharmacologic fixes as opposedto informed, multimodal therapy associated with optimal outcomes.”
This “disturbing prescription practices suggest a growing crisis.”
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