psychopharm for very young children context and guidelines
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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: mgleason@lifespan.org.
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
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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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Copyright @ 2007 American Academy of Child and Adolescent 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.,
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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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Copyright @ 2007 American Academy of Child and Adolescent 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
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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
(
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