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Copyright @ 2007 American Academy of Child and Adolescent
Psychiatry. Unauthorized reproduction of this article is
prohibited.
Psychopharmacological Treatment for Very YoungChildren: Contexts
and Guidelines
MARY MARGARET GLEASON, M.D., HELEN LINK EGGER, M.D., GRAHAM J.
EMSLIE, M.D.,
LAURENCE L. GREENHILL, M.D., ROBERT A. KOWATCH, M.D.,
ALICIA F. LIEBERMAN, PH.D., JOAN L. LUBY, M.D., JUDITH OWENS,
M.D.,
LAWRENCE D. SCAHILL, M.S.N., PH.D., MICHAEL S. SCHEERINGA, M.D.,
M.P.H.,
BRIAN STAFFORD, M.D., M.P.H, BRIAN WISE, M.D., M.P.H., AND
CHARLES H. ZEANAH, M.D.
ABSTRACT
Systematic research and practice guidelines addressing preschool
psychopharmacological treatment in very young
children are limited, despite evidence of increasing clinical
use of medications in this population. The Preschool
Psychopharmacology Working Group (PPWG) was developed to review
existing literature relevant to preschool
psychopharmacology treatment and to develop treatment
recommendations to guide clinicians considering psychophar-
macological treatment in very young children. This article
reviews the developmental considerations related to preschool
psychopharmacological treatment, presents current evidence bases
for specific disorders in early childhood, and
describes the recommended algorithms for medication use. The
purpose of this effort is to promote responsible treatment
of young children, recognizing that this will sometimes involve
the use of medications. J. Am. Acad. Child Adolesc.
Psychiatry, 2007;46(12):1532Y1572. Key Words: preschool,
treatment, psychopharmacology.
In 2000 the American Academy of Child andAdolescent Psychiatry_s
Research Forum highlightedthe developmental, logistical, and
ethical challenges
related to preschool psychopharmacological research(Greenhill et
al., 2003). The group recommended thedevelopment of guidelines for
the pharmacologicaltreatment of preschoolers with psychiatric
disorders.Where randomized controlled data were not available,the
group recommended that guidelines be derivedfrom clinical
experience and community standards. Todate, our field lacks these
guidelines. Thus, cliniciansand families face a delicate balancing
process, weighingthe risks of medications with the risks of not
interveningin complex clinical situations that are resistant
tononpharmacological interventions. The risks associatedwith
psychiatric disorders are not insignificant; pre-school psychiatric
disorders can be associated with childcare expulsion, inability to
participate in familyactivities, impaired peer relationships,
high-risk beha-viors (Byrne et al., 2003; Egger and Angold,
2006;Gilliam, 2005), and future mental health problems(e.g.,
Lavigne et al., 1998).
WORKING GROUP METHODS
The Preschool Psychopharmacology WorkingGroup (PPWG) was
established in response to the
Accepted July 10, 2007.Dr. Gleason is with the Bradley Hasbro
Research Center and the Tulane
Institute of Infant and Early Childhood Mental Health; Dr. Egger
is with theCenter for Developmental Epidemiology, Duke University
Medical School; Dr.Emslie is with the University of Texas
Southwestern Medical Center; Dr.Greenhill is with the New York
State Psychiatric Institute; Dr. Kowatch is withthe Department of
Psychiatry, Cincinnati Children_s Hospital Medical Center;Dr.
Lieberman is with the Department of Psychiatry, University of
California,San Francisco; Dr. Luby is with the Department of
Psychiatry, WashingtonUniversity School of Medicine; Dr. Owens is
with the Department of Pediatrics,Brown University Medical School;
Dr. Scahill is with the Child Study Center atYale University; Dr.
Scheeringa is with the Division of Child and AdolescentPsychiatry
at the Tulane University Health Sciences Center; Dr. Stafford is
withthe Departments of Pediatrics and Psychiatry at the Children_s
Hospital, Denver;Dr. Wise is with the University of Colorado Health
Sciences Center; Dr. Zeanahis with the Division of Child and
Adolescent Psychiatry at Tulane UniversityHealth Sciences
Center.
This project was supported by a grant from the AACAP Abramson
Fund.The authors would like to acknowledge the important
contributions of the
young children and families with whom we work, and the valuable
feedbackreceived from the Early Childhood Clinical Research team at
Bradley Hospital.
Correspondence to Mary Margaret Gleason, M.D., Bradley Hasbro
ResearchCenter, 1 Hoppin Street, Providence, RI 02903; e-mail:
[email protected].
0890-8567/07/4612-15322007 by the American Academy of Childand
Adolescent Psychiatry.
DOI: 10.1097/chi.0b013e3181570d9e
S P E C I A L C O M M U N I C A T I O N
1532 J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 46:12, DECEMBER
2007
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Copyright @ 2007 American Academy of Child and Adolescent
Psychiatry. Unauthorized reproduction of this article is
prohibited.
clinical needs of preschoolers being treated
withpsychopharmacological agents and the absence ofsystematic
practice guidelines for this age group. Thecentral aim of this
working group is to develop bestpractice algorithms for the use of
psychopharmacolog-ical agents in preschool children based upon
literaturereview, clinical experience, and expert consensus.
Thisdiscussion of psychopharmacological treatment ofseverely
impaired young children is provided as anattempt to promote an
evidence-informed, clinicallysound approach to considering
medications in this agegroup. It is not intended to promote the use
ofmedications. We anticipate that application of thesealgorithms
will result in a reduction in the use ofpsychopharmacological
agents for young children. Theworking group includes professionals
with expertise inearly childhood psychiatric disorders,
psychopharma-cology, general and behavioral pediatrics,
clinicalpsychology, and neurodevelopmental processes.
The working group has met in person and reviewedmaterial via
multiple conference calls and e-mail com-munication. Articles were
identified through PubMedand PsycINFO searches for the period
1990Y2007 usingthe search terms preschool,
psychopharmacology,medications, childhood, stimulants,
anti-depressants, SSRI, neuroleptic, antipsychotic,mood stabilizer,
ADHD, depression, anxiety,OCD, PTSD, sleep disorder,
insomnia,aggression, DBD, conduct disorder, opposi-tional defiant
disorder, bipolar disorder, safety, andprescribing. We reviewed all
of the identified preschoolpsychopharmacology publications as were
relevant.Because of the important influence of older child
andadolescent data on prescribing for preschool children, wealso
reviewed the highest level of evidence in older children.
The group developed treatment algorithms to
guidepsychopharmacological treatment of preschool psychia-tric
disorders using the systematic literature review,survey responses
from practicing clinicians (unpub-lished PPWG survey), and the
research and clinicalexpertise of the working group. The algorithms
are notintended to suggest certainty where none exists. Eachstep of
the algorithm is labeled with the level ofevidence that supports
the step to allow clinicians toconsider systematic approaches to
treatment, to beaware of data as well as extant gaps in evidence
base, andto understand the basis for recommendations. Thealgorithms
that were developed represent the groups
best attempt to integrate data and clinical experience;however,
clinicians may determine that an alternativeapproach is indicated
in a particular clinical situation.
Algorithms can facilitate clinical decisions byexplicitly
identifying clinical decision points, definingstrategic (what to
do) and tactical (how to do it)processes (Emslie et al., 2004b).
They are intended tobe user-friendly and reduce unnecessary
variance inclinical practice patterns. Algorithm
implementation,study of clinical outcomes, and a growing research
basewill guide future changes in treatment recommenda-tions
(Gilbert et al., 1998).
OVERVIEW OF PRESCRIBING PRACTICES
Of preschoolers with psychiatric disorders, only asmall
proportion are referred for mental healthtreatment, and the primary
treatment modality formost very young children is psychotherapeutic
ratherthan psychopharmacological (AACAP, 1997b; Eggerand Angold,
2006; Lavigne et al., 1993). Studies usingvaried methods yielded
estimates that 3 to 9/1,000 U.S.preschoolers received prescriptions
for psychotropicmedications in the 1990s (DeBar et al., 2003;
Zitoet al., 2000). Rates of stimulants and "-agonistprescriptions
increased dramatically between 1991 and1995 in Medicaid populations
(Zito et al., 2000). From1991Y1995, prescription rates for
Medicaid-enrolledpreschoolers approximately doubled, with the
mostnotable increases in atypical antipsychotic and anti-depressant
use, with stable rates of stimulant prescrip-tions (Cooper et al.,
2004; Patel et al., 2005; Zito et al.,2007; Zuvekas et al., 2006).
These population-basedstudies do not link the prescription with
clinicalinformation, and it is possible that some
prescriptionswritten for infants or very young children may, in
fact, beintended to treat uninsured parents.
In addition, these studies do not examine complemen-tary and
alternative medication (CAM) use. In a survey ofparents in an
emergency room (mean age 5.3 years; n =103), 16% of parents
reported giving their child a CAMagent for relaxation (Lanski et
al., 2003). Although thedetails of the use of CAM in preschoolers
are beyond thescope of this article, CAM is a factor in
preschoolersexposure to psychotropic agents (Chan, 2002).
A few studies have examined patterns of prescriptionsfor
children with psychiatric diagnoses. Across a varietyof populations
including community, HMO, and
MEDICATION TREATMENT IN PRESCHOOLERS
1533J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 46:12, DECEMBER
2007
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Copyright @ 2007 American Academy of Child and Adolescent
Psychiatry. Unauthorized reproduction of this article is
prohibited.
Medicaid, the majority of prescriptions written forpreschoolers
are for stimulants (DeBar et al., 2003;Luby et al., 2007; Zito et
al., 2007). In an HMOpopulation including 743 preschoolers with
emotionalor behavioral problems, 16% (n = 120) of diagnosedchildren
received psychopharmacological treatment,most commonly monotherapy
with a stimulant(DeBar et al., 2003). In this study, stimulant use
wasclearly linked to attention-deficit/hyperactivity disorder(ADHD)
and "-agonists to sleep and aggression. Theauthors could not
discern an association betweenantidepressant use and diagnoses or
symptoms. In acommunity sample, Luby et al. (2007) reported that12%
(17/123) of preschoolers with a DSM-IV diagnosishad received
medication for at least 1 month. In bothstudies, slightly less than
80% of preschoolers whoreceived psychopharmacological treatment
also receivedpsychotherapy. A total of 33% of the communitysample
and 74% of the HMO sample received theirprescription from a primary
care provider. In higherrisk populations, such as medically complex
toddlerswith ADHD and psychiatrically hospitalized youngchildren,
reports describe higher rates of psychophar-macological treatment
(57%Y79%) and more prevalentuse of more than one medication (Pathak
et al., 2004;Rappley et al., 1999; Rappley et al., 2002).
Taken together, these early studies of preschool
psy-chopharmacological practice suggest that the majority
ofpreschoolers with mental heath problems do not
receivepsychopharmacological treatment. Access to othermental
health services appears variable. Prescriptionpatterns support the
value of clearly defined treatmentrecommendations for rational use
of medications.
SPECIAL CONTEXTS OF PRESCHOOLPSYCHOPHARMACOLOGY
Treatment decisions involving young children
includeconsideration of developmentally specific assessmentsand
diagnosis, attention to neurodevelopmental andethical factors, and
the existing evidence base.
Assessment
Although a comprehensive discussion of assessmentin preschool
children is beyond the scope of this article,a comprehensive,
developmentally sensitive, and con-textually relevant assessment is
a prerequisite toconsideration of treatment. A number of
resources
can be used to guide this process (AACAP, 1997b;Carter et al.,
2004; DelCarmen-Wiggins and Carter,2004; Zeanah et al., 2000). An
assessment of apreschooler includes multiple appointments,
usesmultiple informants, and usually occurs within thecontext of a
multidisciplinary team. A preschoolpsychiatric evaluation should
address a child_s emo-tional and behavioral symptoms, relationship
patterns,medical history, developmental history and status, aswell
as parental and other environmental stressors andsupports (e.g.,
Egger et al., 2006a). In addition, earlychildhood development is
particularly sensitive to thequality of the caregiverYchild
relationship, as well asfamily, child care, community, and cultural
contexts,which may influence the clinical presentation,
caseformulation, and treatment plan (e.g., Seifer et al.,2001;
Zeanah et al., 1997).
Structured, validated approaches to preschoolpsychiatric
assessments can enhance the informationobtained in an assessment.
These approaches includebrief parent report questionnaires focused
on childsymptomatology, such as the Infant-Toddler SocialEmotional
Assessment (Briggs-Gowan, 1998) or theChild Behavior Checklist 1Y5
(Achenbach andRescorla, 2000), diagnostic interviews including
thePreschool Age Psychiatric Assessment (Egger et al.,2006b), and
structured observations of parentYchildinteractions, such as the
Clinical Problem SolvingProcedure (Crowell and Fleischmann,
2000).
A comprehensive preschool psychiatric assessment isimpractical
in a primary care setting, where manychildren receive their
prescriptions (DeBar et al., 2003;Goodwin et al., 2001). In any
setting, a rationalpreschool treatment plan must be founded upon
anadequate history and mental status examination thatallow a
reasonable biopsychosocial formulation. For aprimary care
prescriber, multiple appointments, collec-tion of collateral
information from other caregivers, andconsultation with the child_s
mental health specialistprovide the foundation for treatment
decisions whileallowing a primary care provider to practice within
thescope of his or her knowledge.
Diagnosis
In clinical practice psychiatric diagnosis generallydrives
treatment planning. Applying diagnoses canfacilitate the clinical
application of research findingsfocused on that diagnosis and can
provide a common
GLEASON ET AL.
1534 J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 46:12, DECEMBER
2007
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Psychiatry. Unauthorized reproduction of this article is
prohibited.
language to describe complex clinical syndromes. Inclinical
practice, most but not all impaired preschoolerswill meet full
criteria for a diagnosis (Keenan et al.,1997). For those who do
not, applying standardnosologies and recognizing subthreshold
disorders canfocus treatment planning.
Two diagnostically sensitive nosologies have beendeveloped to
address concerns about the DSM-IV slack of attention to young
children: the ResearchDiagnostic Criteria: Preschool Age (AACAP
TaskForce on Research Diagnostic Criteria: Infancy Pre-school Age,
2003) and the Diagnostic Criteria: 0Y3R(Zero to Three Diagnostic
Classification Task Force,2005). The Research Diagnostic Criteria:
PreschoolAge are developmentally sensitive,
evidence-informedmodifications of the DSM-IV criteria intended
tointroduce reliability into the assignment of diagnoses
topreschoolers, particularly in the research setting. Therecently
revised Diagnostic Criteria: 0Y3R also addressdevelopmentally
specific clinical presentations of men-tal health problems, focused
primarily on infants andtoddlers and their relationships with
caregivers.
Overall, using developmentally sensitive criteria,psychiatric
disorders can be reliably assessed in childrenas young as 2 years
old (Egger et al., 2006b). Empiricalsupport for specific preschool
diagnoses is somewhatvariable. Some disorders, including major
depressivedisorder (Luby et al., 2003a; Luby et al., 2003b; Lubyet
al., 2003c; Luby et al., 2004b), posttraumatic stressdisorder
(PTSD; Scheeringa et al., 2001; Scheeringaet al., 1995; Scheeringa
et al., 2004; Scheeringa et al.,2005), disruptive behavior
disorders (Keenan andWakschlag, 2002; Keenan and Wakschlag,
2004),ADHD (Lahey et al., 2004; Lahey et al., 1998), andautism
(Lord et al., 2006) have empirical evidence thatsupports convergent
and predictive validity. Otherdisorders, including many anxiety
disorders, have notbeen empirically tested in preschoolers.
Reliable andvalid diagnostic criteria are necessary to develop
empiri-cally supported treatments for preschool disorders.
Nonpharmacological Treatment
Clinical decision making includes consideration ofalternative
therapies. Thus, prescribers should be awareof the growing (but
still limited) evidence base forpsychotherapeutic interventions in
preschoolers. Evidence-supported models of treatment are effective
in decreas-ing aggression and behavioral problems in young
children with disruptive behavior disorders (Eyberg,1988; Hood
and Eyberg, 2003; Webster-Strattonet al., 2004), reducing child
traumatic stress disordersymptoms (Cohen and Mannarino, 1997;
Liebermanet al., 2005; Lieberman et al., 2006). Psychother-apeutic
interventions for preschoolers with PTSD(Scheeringa et al., in
press) and mania-like symptoms(Luby et al., in press) have also
shown promisingpreliminary outcomes, although randomized
con-trolled trials have not yet been published. In ourexperience,
access to these evidence-based psychother-apeutic interventions can
be variable and may belimited by a number of variables including
providertraining, third-party payer restrictions, and
parentalmotivation to participate.
Neurodevelopmental Processes
Biology also influences consideration of psychophar-macological
treatment in young children. The impactof early and/or prolonged
exposure to psychotropicmedications in the preschool period has not
beensystematically studied, but research highlights thesensitivity
of the developing brain. Synaptic density,dopamine receptor
density, and cerebral metabolic ratespeak in the first 3 years of
life and decline oversubsequent decades (reviewed in Shonkoff and
Phillips,2000; Vitiello, 1998). In animal models early
exposureeither to psychotropic agents or stressors can perma-nently
affect distribution of the neurotransmitterreceptors (e.g., Maciag
et al., 2005; Matthews, 2002;Yannielli et al., 1999). Similarly,
abnormal infantpsychophysiological processes are associated with
fetalexposure to maternal psychopathology (Engel et al.,2005; Lundy
et al., 1999; Yehuda et al., 2005). Thesefindings highlight the
potential central nervous systemsensitivity to exogenous factors
including medicationsas well as endogenous stress responses.
Longitudinal studies of childrens early exposure topsychotropic
medications are limited to fetal andneonatal exposure from maternal
antidepressant treat-ment, which provide mixed results. Although
prenatalantidepressant exposure is associated with
measurablechanges in infant pain responsivity and toddler
motorskills (Casper et al., 2003; Oberlander et al.,
2005;Oberlander et al., 2006), no cognitive differences orincreased
rates of internalizing or externalizing symp-toms have been
observed in preschool follow-up (Misriet al., 2006; Nulman et al.,
1997; Oberlander et al.,
MEDICATION TREATMENT IN PRESCHOOLERS
1535J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 46:12, DECEMBER
2007
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Copyright @ 2007 American Academy of Child and Adolescent
Psychiatry. Unauthorized reproduction of this article is
prohibited.
2007). These results highlight the need for futureinvestigations
examining longitudinal studies of pre-schoolers exposed to
psychotropic medications, aboutwhom no neurodevelopmental findings
have beenpublished.
Other organ systems also develop during the firstyears of life.
In preschoolers, medication absorption,distribution, and metabolic
processes can have a signifi-cant impact on the pharmacokinetics of
medications,generally meaning that children need higher doses
toachieve comparable plasma levels (Cote, 2005; Crom,1994). In
practice, this pattern must be balancedwith our knowledge that
preschoolers also experiencemore side effects than older children
and adults(e.g., Greenhill et al., 2006; Wigal et al., 2006).Taken
together, developmental pharmacokinetic issuesand sensitivity to
adverse effects make dosing medica-tions in young children a
delicate balance.
Regulatory and Ethical Context
Finally, and not insignificantly, regulatory and
ethicalconsiderations in preschool psychopharmacologicaltreatment
must be considered. A Food and DrugAdministration (FDA) indication
reflects empiricalsupport, although the lack of an indication does
notnecessarily reflect a lack of evidence (AAP Committee onDrugs,
2002). In the United States, only a smallproportion of medications
are approved for use inpediatrics and medications are commonly used
off-label (AAP Committee on Drugs, 2002; Shah et al.,2007). Four
psychiatric medicationsVhaloperidol,dextroamphetamines,
chlorpromazine, and risperidone-are approved for children under age
6 years (Greenhill,1998). The FDA has developed incentives to
encouragethe development and testing of medications for
children,but to date progress is limited for children under
6(Balakrishnan et al., 2006; FDA, 2002; Grieve et al.,2005).
Recently, concerns about the safety of medica-tions in children
have resulted in further regulatoryactions including black box
warnings on selectiveserotonin reuptake inhibitors (SSRIs) in the
UnitedStates and temporary suspension of mixed amphetaminesalts
because of concerns of possible adverse cardiovas-cular effects in
Canada in 2005 (FDA, 2005a; FDA,2005b).
In this context, although off-label use of medicationsis
acceptable, informed consent requires clear, thoroughdiscussions
with parents about the FDA status of a
medication and the level of evidence supporting
therecommendation, potential risks, benefits, and alter-natives to
its use (Jensen, 1998). In the context of apreschoolers psychiatric
disorder, parental distressrelated to the child_s disorder or other
pressures mayaffect a parents participation in the informed
consentprocess (Spetie and Arnold, 2007). Thus, in
preschooltreatment planning, the ethical principles of
autonomy,justice, and beneficence are worthy of special
attention(Spetie and Arnold, 2007).
CONSIDERING PSYCHOPHARMACOLOGICALTREATMENT
The contextual factors reviewed here render rationalprescribing
considerably more challenging for pre-school children compared to
older children. Jensenhas argued, however, that these diagnostic,
neurode-velopmental, metabolic, and regulatory considerationsdo not
comprise a universal proscription against theuse of medication in
young children (Jensen, 1998,p. 588). A child with moderate to
severe symptomsand functional impairment that persist despite
appro-priate psychotherapeutic interventions may be betterserved by
a carefully monitored medication trial thanby continuing other
ineffective treatments. For somechildren, the safety concerns and
developmental risksrelated to the psychiatric disorder may outweigh
safetyconcerns related to planful psychopharmacologicaltreatments.
Our group recommends that trial ofevidence-supported psychosocial
treatments precedepsychopharmacological treatments. In the
authors_view, psychopharmacological treatment is not indicatedfor
preschoolers with only mild or single-contextsymptomatology or
impairment.
Evidence Base
The algorithm section of this article describes thedetails of
diagnosis-specific treatment reports, whichinclude one multisite,
randomized placebo-controlledtrial (Greenhill et al., 2006), as
well as case reports andopen trials (see Table 1). Although these
studies providethe foundation for further studies of
preschoolpsychopathology and treatment, there is not yet abroad
evidence base for the use of most psychotropicmedications in
children under 6 years of age. In thecurrent context clinicians
must also consider studiesusing older populations and their own
clinical experiences
GLEASON ET AL.
1536 J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 46:12, DECEMBER
2007
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Psychiatry. Unauthorized reproduction of this article is
prohibited.
TABLE1
Pu
blis
hed
Pre
sch
ool
Psy
chop
har
mac
olog
ySt
ud
ies
(Mea
nA
ge
-
Copyright @ 2007 American Academy of Child and Adolescent
Psychiatry. Unauthorized reproduction of this article is
prohibited.
TABLE1.
(Con
tinue
d)
Dis
ord
erA
uth
ors
Med
icat
ion
Met
hod
Age
,y
ND
ose
Ou
tcom
eA
E
Bip
olar
:
aggr
essi
on,
moo
din
stab
ilit
y,
man
icsy
mp
tom
s+
bip
olar
fam
ily
his
tory
Hag
ino
etal
.,
1995
Li
Ret
rosp
ecti
vech
art
revi
ewof
AE
4Y6
20W
ith
AE
:37
.2
mg/
kg
60%
had
atle
ast
1A
E(5
0%C
NS,
25%
GI,
10%
GU
)
No
AE
:31
.5
mg/
kg
20%
had
seri
ous
AE
Hig
her
Li
leve
las
soci
ated
wit
hh
igh
erra
tes
ofA
E
Hig
her
rate
sof
AE
asso
ciat
edw
ith
dia
gnos
isof
bip
olar
dis
ord
er
Bip
olar
Bie
der
man
etal
.,
2005
b
Ola
nza
pin
ean
d
risp
erid
one
Op
entr
ial
4Y6
31(1
6
risp
erid
one,
15 olan
zep
ine)
Ris
per
idon
e:
0.25
mg
q.d
.
titr
ated
tom
ax
2.0
mg
q.d
.
Ris
per
idon
e:d
ecre
ase
18.3
T11
.9p
oin
ts
onY
MR
S
Wei
ght
gain
:
risp
erid
one:
2.2
+0.
4kg
;
olan
zap
ine:
3.2
+0.
7kg
over
8w
k
Ola
nza
pin
e:
1.25
mg
q.d
.
titr
ated
tom
ax
10m
gq.
d.
Ola
nza
pin
e12
.1T
10.4
poi
nts
onY
MR
S
Incr
ease
inp
rola
ctin
leve
ls:
risp
erid
one:
12.0
T10
.4;
olan
zap
ine:
7.6T
4.1
Bip
olar
Sch
effe
ret
al.,
2004
AE
D,
stim
ula
nts
,
atyp
ical
anti
psy
chot
ic
agen
ts,
(17
DV
P
mon
oth
erap
y,ot
her
s
pol
yph
arm
acy)
Ret
rosp
ecti
vech
art
revi
ew
2Y5
31N
otp
rese
nte
dSi
gnif
ican
td
ecre
ase
inY
MR
Sat
2m
o(3
4.7Y
13.8
;n
=22
),
non
sign
ific
ant
dec
reas
eon
CG
I-S
(5.0Y3
.3)
Not
pre
sen
ted
No
chan
gein
YM
RS
from
2m
oto
exte
nd
edfo
llow
-up
of1Y
2y;
n=
11
Bip
olar
:m
ania
Mot
a-C
asti
llo
etal
.,20
01
Val
pro
ate
Ret
rosp
ecti
vech
art
revi
ew
21m
oY5
y9
250Y
500
mg
q.d
.
Lev
els:
72Y8
62
/dL
not
hit
tin
gI
mor
eco
oper
ativ
e;
sle
eps
all
nig
ht
wit
hou
t
argu
ingI
slow
edd
own
;
sta
ble
;a
ggre
ssio
n
ceas
ed;
les
sag
gres
siveI
not
def
yin
gor
boss
ing
adu
lts
;i
nsu
ffic
ien
t
follo
w-u
p
(n=
2)
Not
pre
sen
ted
Bip
olar
:m
ania
Tu
mu
luru
etal
.,
2003
Li
(n=
5)+
CB
Z(n
=1)
Ret
rosp
ecti
vech
art
revi
ew
3Y5.
11
(mea
n4.
6)
6N
otad
dre
ssed
Par
ent
refu
sed
Li
(n=
1)
Not
add
ress
ed
Req
uir
edad
dit
ion
of
CB
Z;
sta
ble
;
su
cces
sfu
llytr
eate
d
(n=
2)
Moo
dla
bili
tyd
ecre
ase
Bip
olar
Tu
zun
etal
.,
2002
CB
ZC
ase
rep
ort
5.2
130
0m
gq.
d.
(6.76
g/m
L)
Fu
llre
mis
sion
at5
wk;
recu
rren
ceaf
ter
dis
con
tin
uat
ion
Mil
dse
dat
ion
Nor
mal
bioc
hem
ical
anal
yses
GLEASON ET AL.
1538 J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 46:12, DECEMBER
2007
-
Copyright @ 2007 American Academy of Child and Adolescent
Psychiatry. Unauthorized reproduction of this article is
prohibited.
Bip
olar
:m
ania
(PA
PA
dia
gnos
is)
Pav
ulu
riet
al.,
2002
Top
iram
ate
and
risp
erid
one
Cas
ere
por
t4.
51
Ris
per
idon
e:
0.25
mg
b.i.
d.
Ris
per
idon
em
onot
her
apy:
red
uct
ion
inir
rita
bili
ty
Wei
ght
gain
on
risp
erid
one
mon
oth
erap
y:
15.4
kgin
2m
o
Top
iram
ate
25m
gb.
i.d
.
Top
iram
ate:
moo
d
mor
est
able
,sl
eep
imp
rove
d,
wei
ght
loss
2.7
kg/w
eek
4w
k,
over
all
loss
18.1
kg
Oth
erco
nco
mit
ant
med
s:L
i(p
olyu
ria)
An
xiet
yd
isor
der
s
(sp
ecif
icp
hob
ia,
soci
alan
xiet
y,an
d
feed
ing
anxi
ety)
Han
na
etal
.,
2005
Bu
spir
one
Cas
ere
por
t4
112
.5m
gb.
i.d
.D
ecre
ased
soci
alan
xiet
y,
feed
ing
anxi
ety,
and
spec
ific
ph
obia
sym
pto
ms
Rel
apse
wit
h
dis
con
tin
uat
ion
,
rem
issi
onw
ith
rein
itia
tion
of
trea
tmen
t
An
xiet
y:se
lect
ive
mu
tism
Wri
ght
etal
.,19
95F
luox
etin
eC
ase
stu
dy
4.10
14Y
8m
gq.
d.
Tal
kin
gfr
eely
inal
l
sett
ings
,d
ecre
ased
CB
CL
inte
rnal
izin
gsc
ores
(68Y
60)
Not
add
ress
ed
An
xiet
y:sp
ecif
ic
ph
obia
and
pan
ic
atta
cks
Avc
iet
al.,
1988
Flu
oxet
ine
Cas
ere
por
t2.
51
5m
gq.
d.
(0.2
5m
g/kg
/day
)
Dec
reas
edan
xiet
ysy
mp
tom
s
and
reso
luti
onof
pan
icat
tack
s
Not
add
ress
ed
An
xiet
y:tr
aum
a
rela
ted
Har
mon
and
Rig
gs,
1996
Clo
nid
ine
Op
entr
ial
3Y6
70.
05m
g
titr
ated
to
0.15
mg
q.d
.
Dec
reas
edte
ach
er-r
ated
sym
pto
ms
inat
leas
t>5
/7ch
ild
ren
Con
tact
der
mat
itis
wit
h
pat
ch,
inab
ilit
yto
tole
rate
pat
ch,
1ch
ild
dev
elop
edac
ute
HT
N
wit
hp
osts
trep
toco
ccal
glom
eru
lon
eph
riti
s
(HT
Nth
ough
tto
be
exac
erba
ted
byab
rup
t
dec
lin
eof
clon
idin
e)
PD
DM
asi
etal
.,20
03R
isp
erid
one
Op
entr
ial
36Y7
1m
o53
0.25
mg
titr
ated
up
;
mea
nop
tim
al
dos
e0.
55m
g
47%
imp
rove
dor
very
mu
chim
pro
ved
22%
wit
hd
rew
beca
use
ofA
E
Mea
nw
eigh
tga
in
2.4
(0.9Y9
.5kg
)
over
mea
nof
9m
o
(Con
tinu
edon
next
page
)
MEDICATION TREATMENT IN PRESCHOOLERS
1539J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 46:12, DECEMBER
2007
-
Copyright @ 2007 American Academy of Child and Adolescent
Psychiatry. Unauthorized reproduction of this article is
prohibited.
TABLE1.
(Con
tinue
d)
Dis
ord
erA
uth
ors
Med
icat
ion
Met
hod
Age
,y
ND
ose
Ou
tcom
eA
E
PD
D (au
tism
or
PD
DN
OS)
Lu
byet
al.,
2006
Ris
per
idon
eR
CT
6m
o2.
5Y6.
024
0.5Y
1.5
mg
(mea
nd
ose
1.38
mg)
8%d
ecre
ase
inC
AR
S
scor
ein
risp
erid
one
grou
pvs
.3%
inp
cbgr
oup
Wei
ght
gain
:2.
96kg
inri
sper
idon
egr
oup
vs.
0.61
inp
cbgr
oup
CA
RS
scor
ed
ecre
ased
from
sev
erel
yau
tist
ic
tom
ildYm
oder
ate
in
risp
erid
one
grou
p;
no
chan
gein
pcb
grou
p
Hig
her
incr
ease
in
pro
lact
inle
vel
and
tren
dto
war
dh
igh
er
incr
ease
inle
pti
nle
vels
inri
sper
idon
egr
oup
Tra
nsi
ent
sed
atio
n
(n=
5),
incr
ease
d
app
etit
e(n
=6)
,
hyp
ersa
liva
tion
(n=
2)
inri
sper
idon
egr
oup
PD
DN
agar
ajet
al.,
2006
Ris
per
idon
eR
CT
6m
o2Y
9(m
ean
58Y6
3m
o)
390.
5Y1.
0m
g63
%re
spon
sera
teon
CA
RS
onri
sper
idon
e
(20%
dec
reas
ein
scor
e)
vs.
0%on
pcb
2.8
kgin
crea
sevs
.1.
7(n
s)
onp
cb;
tran
sien
t
(