CanJPsychiatry 2012;57(12):717–721
In Review
A Review of Pharmacoepidemiologic Studies of Antipsychotic
Use in Children and Adolescents
Scott B Patten, MD, PhD1; Waqar Waheed, MD, FRCPC2; Lauren Bresee, PhD3
1
Professor, Departments of Community Health Sciences and Psychiatry, University of Calgary, Calgary, Alberta; Member, Hotchkiss Brain Institute,
University of Calgary, Calgary, Alberta.
Correspondence: 3rd Floor, TRW Building, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6; patten@ucalgary.ca.
2
Graduate Student, Department of Community Health Sciences, University of Calgary, Calgary, Alberta.
3
Post-doctoral Fellow, Department of Medicine, University of Calgary, Calgary, Alberta.
Key Words: risperidone,
aripiprazole, olanzapine,
ziprasidone, paliperidone,
quetiapine, clozapine,
children, adolescent,
pharmacoepidemiology
Received February 2012,
revised, and accepted March
2012.
www.TheCJP.ca
Objective: In Canada, treatment of children and adolescents with antipsychotics is almost
always off label. A single atypical agent, aripiprazole, only recently received regulatory
authorization for use in the group aged 15 to 17 years. This regulatory approval was
restricted to treatment of schizophrenia. The objective of this review was to summarize
pharmacoepidemiologic reports examining the frequency of use of these medications.
Methods: A literature search was used to identify English-language studies examining
the pharmacoepidemiology of antipsychotics in children and adolescents. The results of
identified studies were summarized using narrative review methods.
Results: In countries where longitudinal data are available, increased antipsychotic use
has been consistently observed. Generally, most or all of this increase can be attributed
to second-generation antipsychotics (SGAs). Major international differences are evident
in the literature. European studies describe lower overall frequencies of use than North
American studies (most of which were conducted in the United States). SGAs in children
and adolescents are used more often in boys than in girls, and are increasingly used for
treatment of attention-deficit hyperactivity disorder (ADHD) and conduct disorder (CD).
Conclusions: Determining the most appropriate frequency of SGA use in children and
adolescents will ultimately depend on decisive clarification of risks and benefits. The
currently available literature highlights large international differences in the frequency of use.
These differences may reflect fundamental dissimilarities in the therapeutic stance adopted
toward ADHD and CD by physicians practicing in different countries.
WWW
Objectif : Au Canada, le traitement des enfants et des adolescents par antipsychotiques est
presque toujours non indiqué sur l’étiquette. Un seul agent atypique, l’aripiprazole, a reçu
récemment l’autorisation réglementaire d’utilisation auprès du groupe des 15 à
17 ans. Cette approbation réglementaire se limitait au traitement de la schizophrénie.
L’objectif de cette revue était de résumer les études pharmaco-épidémiologiques qui
examinent la fréquence d’utilisation de ces médicaments.
Méthodes : Une recherche de la littérature a servi à identifier les études en anglais
qui examinent la pharmaco-épidémiologie des antipsychotiques chez les enfants et les
adolescents. Les résultats des études identifiées ont été résumés à l’aide de méthodes de
revue narrative.
Résultats : Dans les pays qui disposent de données longitudinales, une utilisation accrue
des antipsychotiques a été observée régulièrement. Généralement, une grande partie
ou la totalité de cet accroissement peut être attribuée aux antipsychotiques de deuxième
génération (ADG). Des différences majeures entre les pays sont manifestes dans la
littérature. Les études européennes décrivent des fréquences d’utilisation globalement plus
faibles que les études nord-américaines (dont la plupart ont été menées aux États-Unis).
Les ADG chez les enfants et les adolescents sont utilisés plus souvent chez les garçons
que chez les filles, et sont utilisés de plus en plus pour le traitement du trouble de déficit de
l’attention avec ou sans hyperactivité (TDAH) et du trouble des conduites (TC).
Conclusions : La détermination de la fréquence la plus appropriée de l’utilisation des ADG
chez les enfants et les adolescents dépendra en fin de compte de l’éclaircissement risques
et des avantages. La littérature actuelle souligne d’importantes différences entre les pays en
ce qui concerne la fréquence d’utilisation. Ces différences peuvent refléter des dissimilarités
fondamentales dans la position thérapeutique adoptée à l’égard du TDAH et du TC par les
médecins exerçant dans différents pays.
The Canadian Journal of Psychiatry, Vol 57, No 12, December 2012 W 717
In Review
A lthough the classification of antipsychotics into FGAs
and SGAs is somewhat arbitrary,1 the term SGAs
continues to be used to describe a group of antipsychotics
believed to cause fewer extrapyramidal symptoms and to
have a lower risk of tardive dyskinesia than FGAs. Their
introduction has led to major changes in the patterns of use
of antipsychotics. SGAs have become not only generally
preferred agents for the treatment of psychotic disorders
but also increasingly used for a broad set of therapeutic
indications, sometimes without regulatory approval.
Until recently, there were no approved indications for
antipsychotics in children and youth in Canada. Psychotic
disorders, mood disorders, symptoms associated with
pervasive developmental disorders, CDs, ADHD, and
Tourette syndrome are all targets of off-label treatment.
The adverse effects of SGAs include metabolic changes
and weight gain, which can have lifelong implications for
children and adolescents treated with these medications.
The objective of this review was to summarize published
descriptions of the evolving pharmacoepidemiology of
these medications.
Methods
The literature search adopted several strategies. First,
MEDLINE was searched, using OVID and adopting a search
strategy described below. Next, one reviewer reviewed the
abstracts of papers uncovered in this search for relevance
and reviewed the text of papers deemed to be relevant to the
goals of the review. Additional papers were identified because
they were cited in the identified sources or in widely cited
articles.2,3 The MEDLINE search used 3 sets of key words
linked by “or” and these searches were later combined using
“and”. The first set of key words included “antipsychotic.
mp. or exp Antipsychotic Agents/” or “risperidone.mp. or
exp Risperidone/” or “aripiprazole.mp” or “ziprasidone.
mp” or “olanzapine.mp” or “quetiapline.mp” or “clozapine.
mp or exp Clozapine/” or paliperidone.mp”. The second set
included “children.mp. or exp Child/” or “exp Adolescent
Medicine/ or exp Adolescent Psychiatry/ or exp Adolescent/
or exp Adolescent Health Services/ or adolescent.mp”.
Finally, the third set included “exp Epidemiology/ or
epidemiology.mp” or “pharmacoepidemiology.mp. or exp
Pharmacoepidemiology/”.
The literature search was run on January 2, 2012. The
search uncovered 49 unique English-language publications.
Abbreviations
ADHD attention-deficit hyperactivity disorder
CD conduct disorder
DBD disruptive behaviour disorder
FGA first-generation antipsychotic
GP general practitioner
NAMCS National Ambulatory Medical Care Survey
SGA second-generation antipsychotic
718 W La Revue canadienne de psychiatrie, vol 57, no 12, décembre 2012
Clinical Implications
• Canadian pharmacoepidemiologic data on the frequency
of use of SGAs in children and adolescents are scarce.
• Available evidence suggests that use of these
medications in Canada is lower than in the United
States, higher than what has been reported in Italy, and
comparable to that of France and the Netherlands.
Limitations
• International studies are not necessarily comparable
owing to methodological differences.
• While various international studies have reported
divergent estimates, it is impossible to definitively state
what actually are the optimal frequencies.
Review of the abstracts from these papers determined that
5 were pharmacoepidemiologic studies potentially relevant
to the review. These studies were from Italy,4–6 the United
Kingdom,7 and the United States.8 The US study was
found to be a case series concerned with phenothiazine and
butyrophenone poisonings. A large number of additional
pharmacoepidemiologic studies from the United States
and other countries were identified through the scanning of
reference lists, including 2 reviews identified in the search.
One pharmacoepidemiologic study9 reported data only
for the group aged 18 years and older and was therefore
excluded from the review. Among the remaining papers,
6 were not eligible because they did not use population-
based samples, 2 papers were concerned with neurobiology
and (or) pathophysiology, and 7 were pharmacovigilance
reports.10–16 The remaining 26 papers were concerned with
topics not relevant to the review. Finally, one additional
paper that was published after completion of the review was
included because it reported Canadian data.17
Results
European Estimates
While 3 pharmacoepidemiologic studies of antipsychotic
use in Italy were uncovered, age-specific rates were not
reported by 2 of these studies.4,5 A study by Trifiró et al6
focused on general practice registrants aged 15 to 80-plus
years and reported counts of those taking SGAs in the
group aged 15 to 29 years. These counts increased 5-fold
between 1999 and 20026; however, in the population
studied, typical antipsychotics were used more frequently
than atypical antipsychotics in each of the 4 years. This
provided a stark contrast with the situation in some other
countries, as described below. Clavenna et al18 used a multi-
regional drug use monitoring system capable of capturing
nationally reimbursed prescriptions (including risperidone
and olanzapine) within defined populations and thereby
allowing estimation of population rates and trends between
1998 and 2004 in the group aged 0 to 17 years. The study did
not identify a trend toward increasing rates of antipsychotic
use, with the 2004 estimate being 0.68 per 1000 population.
www.LaRCP.ca
 A Review of Pharmacoepidemiologic Studies of Antipsychotic Use in Children and Adolescents
The highest frequency was observed in boys aged 14 to 17
years.
A French study19 reporting the frequency of psychotropic
claims to a large health organization examined a
representative random sample of 6534 children and
adolescents aged 17 years and younger in 2003. Only 9
claims for antipsychotics were identified.19 More than 4300
members of the sample were aged 10 years and younger,
but none of these subjects had a medication claim for an
antipsychotic. However, this study19 was not population
based. A larger study,20 using linkage of administrative
data for 3 national agencies together covering 96.6% of
the French population, reported a prevalence estimate for
antipsychotic use in 2004 of 3.4 per 1000 (4.2 in boys and
2.6 in girls) for the population aged 18 years and younger.
The estimates increased with age, peaking in the category
aged 15 to 18 years at 6.8 per 1000.20
A study conducted in the Netherlands21 used a population
database linked to pharmacy records to estimate population
rates for a geographical area as well as rates of change
over time of antipsychotic use. The prevalence of
antipsychotic use for youth aged 19 years and younger
increased progressively from 3.0 to 6.8 per 1000 between
1997 to 2005, about 10 times higher than the 2004 rate
reported by Clavenna et al18 in Italy, but nearly identical
to population-based French estimates.20 In 1997, the rates
of SGA prescription were lower than those for FGAs (0.6
and 2.5 per 1000, respectively), a pattern that had reversed
by 2005 (5.1 and 2.1 per 1000, respectively). Duration
of antipsychotic use doubled over the same interval to a
median duration of 0.7 years in females and 2.7 years in
males. Both an increased incidence and longer duration of
use are expected to increase prevalence in the population.
Clark7 examined new prescriptions in all 21 Child and
Adolescent Mental Health Services (commonly referred to
as CAMHS) within the Greater Manchester and Lancashire
zones of the North West region of England. A total of
845 new prescriptions were written within two 6-month
periods between 1999 and 2001. At that time, both SGAs
and FGAs were prescribed at about equal frequencies
(7.1% and 7.3% of prescriptions, respectively). The data
could not be used to calculate a population rate. However,
population rates for GP prescriptions of antipsychotics in
the United Kingdom were reported by Rani et al.22 During
the interval examined, between 1992 and 2005, overall
prescriptions nearly doubled, from 0.39 to 0.77 users per
1000 patient-years—the increase was due to increasing use
of SGAs, as prescriptions for FGAs declined during the
interval. These estimates resemble those of Clavenna et al,18
which were also based on a registry of GP prescribing. The
most commonly prescribed SGA was risperidone at 73%.
Consistent with other studies,21,23 there was evidence that
longer durations of use of the medications was contributing
to the increased prevalence of use, as the incidence of new
use did not increase.
www.TheCJP.ca
US Studies
Constantine et al24 used Florida Medicaid claims (fee-for-
service pharmacy, physician services, and institutional
claims) and Medicaid identification numbers to identify
a cohort of children aged 5 years and younger who were
enrolled in the Florida Medicaid program and who initiated
an antipsychotic treatment episode at any time between
July 1, 2003, and June 30, 2004. Risperidone was the most
frequently used antipsychotic (69.5%) and FGAs were
almost never used in this population. Children treated with
antipsychotics were more likely to be male, less likely to be
black or Hispanic, and most commonly had ADHD, DBDs,
or pervasive developmental disorders. Olfson et al25 studied
privately insured children aged 2 to 5 years in the United
States at 2 time points: 1999–2001 and 2007. In contrast to
the European studies, the vast majority of prescriptions were
for SGAs at both time points (89.2% in 1999–2001), with
SGAs being used almost exclusively by 2007 (99.75%). In
2007, the rates varied from 0.32 per 1000 in children aged
2 years to 3.0 per 1000 in children aged 5 years. By way
of comparison, the Netherlands study21 described above
reported a 2005 rate in the group aged 0 to 4 years of 0.3 per
1000 for SGAs and 0.5 for FGAs. Risperidone accounted
for about 75% of prescriptions at each time point in the US
sample.
A broader age range (19 years and younger) was examined
by Patel et al3 using Texas Medicaid data between 1996 and
2000. In 1996, the rate of FGA use (per 1000 enrollees) was
4.94, compared with 2.69 for SGAs. By 2000, these rates
were 3.89 and 15.98, respectively. The greatest relative
increase was seen in children aged 5 to 9 years (where the
rate of use of SGAs increased by 609% during this interval).
However, the highest absolute rates were seen in the group
aged 10 to 14 years. The frequency of use of antipsychotics
among males was about twice that of females. Patel et al3
subsequently examined these results by evaluating similar
data in additional Medicaid programs, and one managed
care organization for the period between 1996 and 2001.
This study3 demonstrated increases in prescription rates
over time, with boys having higher rates than girls and
increased use with age, peaking in 3 of these 4 populations
in the group aged 10 to 14 years. Consistent results were
also found using data from an expanded Medicare program
in Tennessee, called TennCare.26 This study26 found a rapid
increase in use between 1996 and 2001, with predominant
use being in males and the largest increases in indication
for use being ADHD and CD. Lastly, Pathak et al27 also
reported a doubling of SGA use in a later time interval,
between 2001 and 2005, in a state Medicaid population,
pointing toward continued increases.
While the US studies cited above document trends in SGA
use, they derive from specific eligible populations and
cannot be used to estimate general population rates. In
the United States, the NAMCS and the National Hospital
Ambulatory Medical Care Survey, collected representative
data through sampling procedures based on data collected
from physicians, health care sites, or their records. Cooper
The Canadian Journal of Psychiatry, Vol 57, No 12, December 2012 W 719
In Review
et al28 examined these data for the group aged 2 to 18 years
between 1995 and 2002. The mean age at prescription of an
antipsychotic was 12.9 years, and two-thirds of recipients
were male. This study28 estimated the overall rate of
antipsychotic prescriptions to be 39.4 per 1000 per 2-year
interval. The most common indications were ADHD and
(or) CD (29%), and the second most common indicator
was mood disorder (23.6%). Using census data, population
rates were calculated both for the groups aged 2 to 12 and
13 to 18 years; in each case, the prescription rate increased
about 5-fold between 1995/96 and 2001/02, leading to rates
of 26.9 and 63.8 per 1000 in these 2 groups, respectively, by
2001/02. Similar trends, but lower rates, were reported by
Olfson et al2 in an analysis of NAMCS data. These authors
estimated that the annual rate of physician visits that
included an antipsychotic prescription was 1341 per 100 000
in the period between 2000 and 2002. Olfson et al2 reported
that by 2001/02, 92.3% of antipsychotic prescriptions from
visits involving an antipsychotic prescription were for an
SGA, contrasting with persistence of use of FGAs in some
of the European studies. Among youth mental health visits
in which an antipsychotic was prescribed, DBDs (37.8%),
mood disorders (31.8%), pervasive developmental disorders
or mental retardation (17.3%), or psychotic disorders
(14.2%) were the most frequent diagnoses.
Canada
Three Canadian studies were identified. Two of these used the
Manitoba Population Health Research Data Repository,17,29
one of which focused on the child and adolescent age
group.17 The 2008 study did not specifically focus on
children and adolescents, but did report age-specific rates
for the group aged 0 to 18 years. Estimates were found to
increase with time (1996–2006), and although the rates for
FGAs began to decline in 1997, about 20% of antipsychotic
prescriptions in 2006 were for FGAs. In the group 0 to
18 years in 2006, the male rate of antipsychotic use was
8.8 per 1000, whereas it was 3.5 per 1000 for females. A
more recent paper,17 also using the Manitoba Repository,
reported the rate of use of antipsychotics in the group
aged 0 to 18 years to increase from 1.9 per 1000 in 1999
to 7.4 per 1000 in 2008. Consistent with the international
literature, the most common medication was risperidone,
the male-to-female ratio was about 2:1 across the entire
time interval, and the most common diagnoses were ADHD
and CD. These estimates seem fairly close to those reported
in the Netherlands21 and from the population-based study in
France,20 and are lower than those reported by Cooper et al28
using US data. Also, whereas in the US prescriptions for
FGAs appear to have been rare as far back as the late 1990s,
the number of prescriptions for these agents resembled that
for SGAs in Manitoba in 1999, although the use of FGAs
declined after that. In 2008, the proportion of prescriptions
written by GPs in Manitoba was 73%.17
The third study, by Pringsheim et al,30 used IMS Health data
(Canadian Disease and Therapeutic Index) to estimate the
number of prescription recommendations for antipsychotics
720 W La Revue canadienne de psychiatrie, vol 57, no 12, décembre 2012
in the group aged 17 years and younger. Increases both
for SGAs and FGAs were observed, but increases were
much more rapid for SGAs. The most common reasons
for SGA recommendations were ADHD (17%), mood
disorder (16%), CD (14%), and psychotic disorder (13%).
In distinction, the most common reasons for FGAs were a
tic disorder (30%) followed by a psychotic disorder (28%).
While this study30 did not report population rates, it was able
to document relative change during a 5-year time interval: a
114% increase. The vast majority of the recommendations
were for SGAs (95%), and among these risperidone was
the most common medication. The recommendations were
made mostly (62%) by psychiatrists, which is an interesting
observation considering that 2 of the lower-end estimates in
the literature derive from GP databases.18,22 These estimates
differ from the Manitoba studies in that a larger proportion
of recommendations were from psychiatrists, and FGAs
did not decline dramatically over time, as was reported in
Manitoba.
Conclusions
This review uncovered large differences between studies
and across countries in which these studies were conducted.
However, certain commonalities were also identified.
Almost all of the studies reported increases in antipsychotic
use, and the use of SGAs in particular. The findings
reported by European and US studies are divergent in
several respects. One difference is the near disappearance
of FGA prescriptions in the United States. In Europe, FGAs
continue to be used. The most recent Canadian data from
the Pringsheim et al study30 puts Canada closer to the US
pattern in this respect, with 95% of recommendations being
for SGAs and a similar picture was reported in Manitoba.17
Most studies internationally have identified risperidone as
the most widely used SGA in childhood and adolescence.
Other commonalities include the higher rates of use seen
in boys and high rates of use in the group aged 7 years and
older, compared with the group aged 0 to 6 years.
Whereas increasing use of antipsychotics, and SGAs in
particular, has been widely reported, several studies from
this literature indicate that the increase in prevalence is
not due exclusively to an increased frequency of new use,
but also to a longer duration of use. This emphasizes the
importance of safety monitoring.31 Consistent with this,
an Icelandic study reported increasing prevalence between
2003 and 2007, with no apparent change in incidence of
antipsychotic use in the population aged 0 to 17 years.23
The conditions driving the increased use appear most often
to be ADHD, conduct and behavioural disturbances, and,
to a lesser extent, mood disorders. However, the greater
prominence of SGA prescriptions for mood disorders in
some of the US studies and the Pringsheim et al study30
do not align with the Manitoba data, which placed the use
of SGAs for mood disorders far below that of ADHD and
CD.17 The frequency of use of antipsychotics in children
and adolescents in Canada appears to be lower than that of
the United States, more closely resembling estimates from
www.LaRCP.ca
 A Review of Pharmacoepidemiologic Studies of Antipsychotic Use in Children and Adolescents
the Netherlands,21 France,20 and Iceland.23 In turn, these
were higher than UK and Italian estimates from mental
health services and general practice research databases. The
latter may have underestimated the frequency of use as, at
least in Canada, a substantial proportion of antipsychotic
prescriptions for children and adolescents are not written by
primary care physicians.30
Acknowledgements
Dr Patten is a Senior Health Scholar with Alberta Innovates,
Health Solutions. He currently receives research funding
from the Canadian Institutes of Health Research, the
Collaborative Research Grant Initiative, the Institute of
Health Economics, and the Alberta Centre for Child,
Family and Community Research. In 2012, he received
an honorarium for serving on a Pfizer grant review panel.
During the past 3 years he also received payment for
reviewing a grant for Lundbeck, and was paid consulting
fees by Servier, Canada.
The Canadian Psychiatric Association proudly supports the
In Review series by providing an honorarium to the authors.
References
1. Tyrer P, Kendall T. The spurious advance of antipsychotic drug
therapy. Lancet. 2009;373(9657):4–5.
2. Olfson M, Blanco C, Liu L, et al. National trends in the outpatient
treatment of children and adolescents with antipsychotic drugs. Arch
Gen Psychiatry. 2006;63(6):679–685.
3. Patel NC, Crismon ML, Hoagwood K, et al. Trends in the use of
typical and atypical antipsychotics in children and adolescents. J Am
Acad Child Adolesc Psychiatry. 2005;44(6):548–556.
4. Mirandola M, Andretta M, Corbari L, et al. Prevalence, incidence
and persistence of antipsychotic drug prescribing in the Italian
general population: retrospective database analysis, 1999–2002.
Pharmacoepidemiol Drug Saf. 2006;15(6):412–420.
5. Percudani M, Barbui C, Fortino I, et al. Epidemiology of first-
and second-generation antipsychotic agents in Lombardy, Italy.
Pharmacopsychiatry. 2005;38(3):128–131.
6. Trifiró G, Spina E, Brignoli O, et al. Antipsychotic prescribing
pattern among Italian general practitioners: a population-based
study during the years 1999–2002. Eur J Clin Pharmacol.
2005;61(1):47–53.
7. Clark AF. Incidences of new prescribing by British child and
adolescent psychiatrists: a prospective study over 12 months.
J Psychopharmacol. 2004;18(1):115–120.
8. James LP, Abel K, Wilkinson J, et al. Phenothiazine, butyrophenone,
and other psychotropic medication poisonings in children and
adolescents. J Toxicol Clin Toxicol. 2000;38(6):615–623.
9. Sankaranarayanan J, Puumala SE. Epidemiology and characteristics
of emergency departments visits by US adults with psychiatric
disorder and antipsychotic mention from 2000 to 2004. Curr Med
Res Opin. 2007;23(6):1375–1385.
10. Montastruc G, Favreliere S, Sommet A, et al. Drugs and
dilated cardiomyopathies: a case/noncase study in the
French PharmacoVigilance Database. Br J Clin Pharmacol.
2010;69(3):287–294.
11. Forrester MB, Forrester MB. Aripiprazole exposures reported to
Texas poison control centers during 2002–2004. J Toxicol Environ
Health A. 2006;69(18):1719–1726.
12. Koller EA, Weber J, Doraiswamy PM, et al. A survey of reports of
quetiapine-associated hyperglycemia and diabetes mellitus. J Clin
Psychiatry. 2004;65(6):857–863.
www.TheCJP.ca
13. Pascoe SJ. The adjunctive use of a centralised database in the
monitoring of clozapine-related neutropenia. Pharmacoepidemiol
Drug Saf. 2003;12(5):395–398.
14. Kornegay CJ, Vasilakis-Scaramozza C, Jick H, et al. Incident
diabetes associated with antipsychotic use in the United
Kingdom general practice research database. J Clin Psychiatry.
2002;63(9):758–762.
15. Spila-Alegiani S, Diana G, Menniti-Ippolito F, et al.
Anticholinergic antiparkinsonian therapy in outpatients treated with
neuroleptic drugs: a prescription survey. Eur J Clin Pharmacol.
1995;48(6):513–517.
16. Bateman DN, Rawlins MD, Simpson JM, et al. Extrapyramidal
reactions to prochlorperazine and haloperidol in the United
Kingdom. Q J Med. 1986;59(230):549–556.
17. Alessi-Severini S, Biscontri RG, Collins DM, et al. Ten years of
antipsychotic prescribing to children: a Canadian population-based
study. Can J Psychiatry. 2012;57(1):52–58.
18. Clavenna A, Rossi E, Derosa M, et al. Use of psychotropic
medications in Italian children and adolescents. Eur J Pediatr.
2007;166(4):339–347.
19. Sevilla-Dedieu C, Kovess-Masfety V. Psychotropic medication use
in children and adolescents: a study from France. J Child Adolesc
Psychopharmacol. 2008;18(3):281–289.
20. Acquaviva E, Legleye S, Auleley GR, et al. Psychotropic medication
in the French child and adolescent population: prevalence estimation
from health insurance data and national self-report survey data.
BMC Psychiatry. 2009;9:72.
21. Kalverdijk LJ, Tobi H, van den Berg PB, et al. Use of antipsychotic
drugs among Dutch youths between 1997 and 2005. Psychiatr Serv.
2008;59(5):554–560.
22. Rani F, Murray ML, Byrne PJ, et al. Epidemiologic features of
antipsychotic prescribing to children and adolescents in primary care
in the United Kingdom. Pediatrics. 2008;121(5):1002–1009.
23. Zoega H, Baldursson G, Hrafnkelsson B, et al. Psychotropic drug
use among Icelandic children: a nationwide population-based study.
J Child Adolesc Psychopharmacol. 2009;19(6):757–764.
24. Constantine RJ, Tandon R, McPherson M, et al. Early diagnoses
and psychotherapeutic medication treatment experiences of a cohort
of children under 6 years old who received antipsychotic treatment
in Florida’s Medicaid program. J Child Adolesc Psychopharmacol.
2011;21(1):79–84.
25. Olfson M, Crystal S, Huang C, et al. Trends in antipsychotic drug
use by very young, privately insured children. J Am Acad Child
Adolesc Psychiatry. 2010;49(1):13–23.
26. Cooper WO, Hickson GB, Fuchs C, et al. New users of
antipsychotic medications among children enrolled in TennCare.
Arch Pediatr Adolesc Med. 2004;158(8):753–759.
27. Pathak P, West D, Martin BC, et al. Evidence-based use of second-
generation antipsychotics in a state Medicaid pediatric population,
2001–2005. Psychiatr Serv. 2010;61(2):123–129.
28. Cooper WO, Arbogast PG, Ding H, et al. Trends in prescribing
of antipsychotic medications for US children. Ambul Pediatr.
2006;6(2):79–83.
29. Alessi-Severini S, Biscontri RG, Collins DM, et al. Utilization and
costs of antipsychotic agents: a Canadian population-based study,
1996–2006. Psychiatr Serv. 2008;59(5):547–553.
30. Pringsheim T, Lam D, Patten SB. The pharmacoepidemiology of
antipsychotic medications for canadian children and adolescents:
2005–2009. J Child Adolesc Psychopharmacol.
2011;21(6):537–543.
31. Pringsheim T, Panagiotopoulos C, Davidson J, et al. Evidence-
based recommendations for monitoring safety of second generation
antipsychotics in children and youth. J Can Acad Child Adolesc
Psychiatry. 2011;20(3):218–233.
The Canadian Journal of Psychiatry, Vol 57, No 12, December 2012 W 721