CanJPsychiatry 2012;57(12):722–727
In Review
Second-Generation Antipsychotics for the Treatment of
Disruptive Behaviour Disorders in Children:
A Systematic Review
Tamara Pringsheim, MD, MSc1; Daniel Gorman, MD2
1
Assistant Professor, Department of Clinical Neurosciences, Psychiatry, and Pediatrics, University of Calgary, Calgary, Alberta.
Correspondence: Alberta Children’s Hospital, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8; tmprings@ucalgary.ca.
2
Assistant Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario.
Key Words: second-generation
antipsychotics, disruptive
behaviour disorders, attention-
deficit hyperactivity disorder,
conduct disorder, oppositional
defiant disorder, children
Received and accepted March
2012.
722 W La Revue canadienne de psychiatrie, vol 57, no 12, décembre 2012
Objective: The use of second-generation antipsychotics (SGAs) in youth has increased
considerably. Increases are mainly attributable to treatment of disruptive behaviour disorders
(DBDs). Our objective was to review the evidence regarding the efficacy of SGAs for DBDs
in youth.
Method: We performed a systematic review of all randomized controlled trials (RCTs) of
SGAs and placebo for the treatment of DBDs in youth, focusing on efficacy data.
Results: Eight RCTs in youth with DBDs were included. Five RCTs evaluated the use
of risperidone in youth with the combination of subaverage–borderline IQ and disruptive
behaviour–aggression. Single RCTs evaluated the use of risperidone for treatment-resistant
aggression in attention-deficit hyperactivity disorder and for the treatment of conduct disorder
(CD), and a single RCT evaluated the use of quetiapine for adolescent CD. The efficacy
results of each of these studies are described.
Conclusion: Four placebo-controlled studies support the short-term efficacy of low-
dose risperidone in youth with a subaverage IQ. Placebo-controlled evidence is weak or
nonexistent for SGAs other than risperidone, and is weak in youth with an average IQ.
Multiple factors likely account for the disconnect between this limited evidence base and the
frequent use of SGAs for DBDs in clinical practice. These include extrapolation from studies
in youth with autism or a subaverage IQ to normally developing youth; ease of SGA titration
and the mistaken perception that little monitoring is required; unavailability of psychosocial
treatments; limited familiarity with other pharmacological options; clinical and cultural norms;
and the influence of the pharmaceutical industry.
WWW
Objectif : L’utilisation d’antipsychotiques de deuxième génération (ADG) chez les
adolescents s’est accrue considérablement. Ces accroissements sont principalement
attribuables au traitement des troubles de comportement perturbateur (TCP). Notre objectif
était d’examiner les données probantes concernant l’efficacité des ADG pour les TCP chez
les adolescents.
Méthode : Nous avons effectué une revue systématique de tous les essais randomisés
contrôlés (ERC) portant sur les ADG et les placebos pour le traitement des TCP chez les
adolescents, en mettant l’accent sur les données d’efficacité.
Résultats : Huit ERC sur les adolescents souffrant de TCP ont été inclus. Cinq ERC
évaluaient l’utilisation de la rispéridone chez les adolescents présentant une combinaison
de QI limite inférieur à la moyenne et de comportement perturbateur-agressif. Des ERC
individuels évaluaient l’utilisation de la rispéridone pour l’agressivité réfractaire au traitement
dans le trouble de déficit de l’attention avec ou sans hyperactivité et pour le traitement du
trouble des conduites (TC), et un seul ERC évaluait l’utilisation de la quétiapine pour le TC
adolescent. Les résultats d’efficacité de chacune de ces études sont décrits.
Conclusion : Quatre études contrôlées contre placebo soutiennent l’efficacité à court terme
de la rispéridone à faible dose chez les adolescents ayant un QI inférieur à la moyenne.
Les données probantes du contrôle contre placebo sont faibles ou inexistantes pour les
ADG autres que la rispéridone, et sont faibles chez les adolescents ayant un QI moyen. De
multiples facteurs expliquent vraisemblablement la disparité entre cette base factuelle limitée
et l’utilisation fréquente des ADG pour les TCP dans la pratique clinique. Ce sont notamment
le fait d’extrapoler des études d’adolescents souffrant d’autisme ou d’un QI inférieur à la
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 Second-Generation Antipsychotics for the Treatment of Disruptive Behaviour Disorders in Children: A Systematic Review
normale à des adolescents au développement normal; la facilité de titration des ADG et la perception erronée que
très peu de surveillance suffit; la non-disponibilité de traitements psychosociaux; la familiarité limitée avec d’autres
options pharmacologiques; les normes cliniques et culturelles; et l’influence de l’industrie pharmaceutique.
D uring the past decade, the use of SGAs in children and
adolescents has increased considerably in Canada1
and other developed countries.2 Increases in medication
use have been mainly attributable to the prescription of
SGAs for a wide variety of nonpsychotic disorders, with
the greatest increase for the treatment of the DBDs. The
increased use of SGAs in Canadian youth is concerning,
particularly because the only pediatric approval of an SGA
by Health Canada is for aripiprazole in adolescents (aged
16 years and older) with schizophrenia. Further, SGAs are
associated with metabolic and neurological side effects that
require monitoring and vigilance on the part of both the
practitioner and the parent.3 Our objective was to review the
evidence for the efficacy of SGAs in children with DBDs in
an effort to clarify how strongly the literature supports their
increased use for this indication in clinical practice.
Methods
We searched for all RCTs of SGAs, compared with placebo,
for the treatment of DBDs (such as ADHD, ODD, and CD,
as well as aggressive behaviour in children with these
disorders). Both the MEDLINE and Embase databases
were searched, from 1996 to September of 2011, for
relevant articles (see MEDLINE search strategy in online
eAppendix  1). Studies comparing SGAs to an active
comparator were excluded, as were open-label studies.
There were no restrictions about language of publication
Abbreviations
ABC Aberrant Behaviour Checklist
ADHD attention-deficit hyperactivity disorder
CAS-P Children’s Aggression Scale—Parent
CAS-T CAS—Teacher
CBCL Child Behaviour Checklist
CD conduct disorder
CGI Clinical Global Impression
CGI-I CGI—Improvement
CGI-S CGI—Severity
CPRS Conners Parent Rating Scale
DBD disruptive behaviour disorder
DSM Diagnostic and Statistical Manual of Mental Disorders
NCBRF Nisonger Child Behaviour Rating Form
NOS not otherwise specified
OAS Overt Aggression Scale
ODD oppositional defiant disorder
RAAPP Rating of Aggression Against People and/or Property
RCT randomized controlled trial
SGA second-generation antipsychotic
www.TheCJP.ca
Clinical Implications
• There is good evidence to support the short-term
efficacy of risperidone for the treatment of DBDs in
children with subaverage IQs.
• Evidence is weak for the use of SGAs in the treatment
of DBDs in children with average IQs.
Limitations
• All published RCTs have been funded by pharmaceutical
companies.
• The number of published studies and the number of
participants in these studies is modest.
or size of study. All abstracts retrieved from the searches
were examined by 2 reviewers, independently, for
potential inclusion. Full text articles of relevant abstracts
were retrieved and read in detail by each reviewer,
independently. Data were abstracted in duplicate onto
predesigned summary forms and confirmed for accuracy.
The methodological quality of studies was evaluated using
quality criteria proposed by the US Preventive Services
Task Force.4 Based on fulfillment of quality criteria, studies
were rated as good, fair, or poor (see list of quality criteria
in online eAppendix 2).
For the purposes of this review, we focused on drug efficacy
data. For information on adverse events, the reader is
referred to a published systematic review of adverse effects
related to SGA use in children.5
Results
A total of 8 RCTs of SGAs, compared with placebo, in youth
with DBDs were included in this systematic review (online
eTable 1). Methodological quality of included studies was
good or fair for all included trials. All studies were sponsored
by pharmaceutical companies. We found 2 additional RCT
protocols registered on the clinical trials.gov website, for
which no results were available through the website or in
the published literature. This included 1 RCT of aripiprazole
for ADHD with partial or no response to stimulants, and 1
RCT of ziprasidone for CD or other DBDs.
Five RCTs have evaluated the use of risperidone in youth
with the combination of subaverage–borderline IQ and
disruptive behaviour–aggression.6–9 Single RCTs have
evaluated the use of risperidone for treatment-resistant
aggression in ADHD10 and for the treatment of CD,11
and a single RCT has evaluated the use of quetiapine for
adolescent CD.12
Snyder et al13 performed a 6-week double-blind study of 110
children, aged 5 to 12 years, with an IQ between 36 and 84,
a DBD (DSM-IV diagnosis of CD, ODD, or DBD-NOS),
and a score of at least 24 on the Conduct Problem subscale
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In Review
of the NCBRF, parent version. Eighty per cent of subjects
had comorbid ADHD. The mean dosage of risperidone was
0.98 mg daily, given once in the morning. Subjects taking
previously prescribed stable dosages of psychostimulants
for 30 days prior to trial entry were included. The primary
outcome variable for the study was the Conduct Problem
subscale of the NCBRF at week 6 of the double-blind
treatment phase. Children completed a 1-week, single-blind
placebo, run-in period to exclude placebo responders.
One hundred and thirty-three children were admitted to the
study: 23 were placebo responders, leaving 110 children
who were randomized to treatment with risperidone or
placebo. The placebo and risperidone groups did not
differ in any baseline demographic features. Twenty-five
children discontinued before completion of the trial: 19
from the placebo group and 6 from the risperidone group.
All 19 children in the placebo group discontinued because
of insufficient response, compared with 2 children in the
risperidone group (P < 0.001). Changes from baseline to end
point on the Conduct Problem subscale of the NCBRF were
significantly greater in the risperidone group, compared
with the placebo group, with a decline in symptom ratings
of 6.8 points with placebo and 15.8 points with risperidone
(P < 0.001). A significant effect was demonstrated from the
first week of treatment onward. In addition to the primary
end point, numerous secondary efficacy variables showed
significant improvement, including all 5 subscales of the
ABC.
Aman et al7 performed an identical study to Snyder et al13 in
118 children, using the same study design, inclusion criteria,
and outcome measures. Demographic characteristics of
the risperidone and placebo groups differed regarding IQ,
with a mean IQ of 66 in the placebo group and 70 in the
risperidone group (P < 0.04). Because of this difference,
IQ was controlled for statistically. Twelve risperidone
subjects and 19 placebo subjects withdrew prematurely.
Discontinuation owing to insufficient response occurred in
15 placebo subjects, compared with 4 risperidone subjects.
The mean dosage of risperidone at end point was 1.16 mg
daily. The risperidone group had a significantly greater
decrease in the Conduct Problem subscale of the NCBRF,
compared with the placebo group, at end point, with a
decrease in score of 15.2 points, compared with 6.2 points
with placebo (P < 0.001). A significant difference in mean
change scores between groups occurred at week 1 of the
trial and was maintained throughout the 6-week study.
Compared with placebo, risperidone-treated children had
significantly greater improvement on numerous secondary
efficacy variables, including all other subscales of the
NCBRF and 3 of 5 subscales of the ABC.
Van Bellinghen and De Troch6 performed a 4-week RCT
in 13 children and adolescents in residential care with
subaverage–borderline IQ and disruptive behaviour–
aggression. Patients aged 6 to 18 years who had IQs
between 45 and 85 and demonstrated persistent behav-
ioural disturbances (hostility, aggressiveness, irritability,
724 W La Revue canadienne de psychiatrie, vol 57, no 12, décembre 2012
agitation, or hyperactivity) were eligible for inclusion.
Antiepileptic medications were allowed during the trial, but
other psychotropics were not permitted. Subjects received
a mean dosage of 1.2 mg daily, given in the evening. A
primary outcome measure was not specified, but subjects
were assessed at baseline and end point using the ABC, CGI
scale, and various other scales.
There were no significant differences between treatment
groups at baseline, and all patients completed the study.
Significant differences between risperidone and placebo at
end point were noted in 3 of the ABC subscales and the CGI
mean scores. The ABC total score decreased by 30.3 points
with risperidone, compared with 3.3 points with placebo
(P < 0.01). Mean score on the CGI decreased by 2.2 points
in the risperidone group, compared with 0.2 points in the
placebo group (P < 0.05). Five of 6 subjects randomized
to risperidone were rated as much or very much improved,
compared with none of the 7 subjects randomized to
placebo.
Buitelaar et al8 compared risperidone to placebo for
aggression in a 10-week trial of 38 hospitalized adolescents
with subaverage IQ. Study subjects were institutionalized
for a chronic pattern of repetitive aggressive behaviour that
was refractory to outpatient treatment approaches, although
not all patients had received prior drug therapy. Subjects
were included in the study if they were aged between 12
and 18 years with a principal diagnosis of CD, ODD, or
ADHD and a full-scale IQ between 60 and 90. Subjects
had to have overt aggressive behaviour that persisted
during hospitalization and failed to respond to behavioural
treatment approaches. The use of concomitant psychotropics
was not permitted during the double-blind treatment phase
of the study. The mean dosage of risperidone in the trial
was 2.9 mg daily (total; administered twice daily). The
primary efficacy measure was the overall severity of the
subject’s condition, as assessed by a psychiatrist on the
CGI-S scale. The trial design included a 2-week baseline
period, a 6-week double-blind treatment period, and a
2-week washout period. Patients were permitted to take
psychotropics during the 2-week baseline period, but it was
discontinued at the beginning of the 6-week double-blind
treatment phase.
Two subjects in the placebo group stopped treatment during
the double-blind period because of lack of improvement
and uncontrollable aggressive behaviour. One subject in the
risperidone group terminated the study following 1 week in
the washout period because of unmanageable aggression.
On the primary outcome measure, risperidone was superior
to placebo after 2 weeks of treatment and throughout the
remainder of the treatment period. Mean CGI-S scores were
4.3 (SD 1.4) at baseline and 2.7 (SD 1.2) at end point in the
risperidone group, in contrast to 4.2 (SD 0.9) at baseline and
4.4 (SD 1.0) at end point in the placebo group (P < 0.001).
During the washout period, subjects treated with risperidone
showed a significantly greater deterioration than placebo-
treated subjects. The OAS and ABC were used as secondary
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 Second-Generation Antipsychotics for the Treatment of Disruptive Behaviour Disorders in Children: A Systematic Review
measures and were completed separately by ward staff
and teachers. Subjects in the risperidone group showed
significant improvement in scores at end point, compared
with baseline, while the placebo group did not. However,
differences in change scores between groups were not
significant, with the exception of the change in overall ABC
score as rated by teachers.
Reyes et al9 performed an RCT of risperidone maintenance
treatment in children and adolescents meeting DSM-IV
criteria for CD, ODD, or DBD-NOS. This study had 335
subjects with normal or subaverage IQ (that is, an IQ of 56
or more). Inclusion required that the conduct problem be
serious enough to warrant treatment with risperidone, as well
as a score of 25 or more on the Conduct Problem subscale
of the NCBRF, parent version. Concomitant therapy with
a stable dose of psychostimulant was permitted. Subjects
who had previously responded to risperidone treatment
during 12 weeks were randomly assigned to 6 months of
double-blind risperidone or placebo. The primary outcome
was the time to symptom recurrence, which was defined
as sustained deterioration on either the CGI-S rating (of
2 or more points) or the Conduct Problem subscale of
the NCBRF (of 7 or more points). Risperidone dosage
was based on weight, with patients less than 50 kg receiving
0.25 to 0.75 mg daily, and patients more than 50 kg
receiving 0.5 to 1.5 mg daily (given once daily or twice in
divided doses).
Five hundred and twenty-seven subjects entered the initial
open-label, 6-week risperidone acute treatment phase.
Among these, 436 subjects continued 6 weeks of single-
blind risperidone therapy (the single-blind phase was
employed to ensure that the patient and the caregiver
were unaware of the exact timing of the randomization to
risperidone or to placebo). Among the 91 subjects who did
not continue, 52 stopped because of nonresponse. Three
hundred and thirty-five subjects then entered the 6-month,
double-blind maintenance treatment; of the 101 children
who did not continue, 61 stopped because of nonsustained
response. In the maintenance phase, 172 subjects were
randomized to risperidone and 163 to placebo. At the end
of this period, a significant difference was found in the rates
of symptom recurrence, with 27.3% of subjects assigned
to risperidone meeting criteria for recurrence, compared
with 42.3% assigned to placebo (P = 0.002). Further,
symptom recurrence occurred in 25% of subjects after 119
days with risperidone, compared with 37 days with placebo
(P < 0.001).
Armenteros et al10 evaluated the efficacy of risperidone
augmentation for treatment-resistant aggression in an RCT
involving 25 children (aged 7 to 12 years) with ADHD on a
constant dose of a psychostimulant. Subjects had aggressive
behaviours that failed to respond to psychostimulant therapy
as documented by 3 acts of aggression in the past week, 2
of which had to be acts of physical aggression against other
people, objects, or self. Full-scale IQ had to be 76 or more.
Children were randomized to risperidone (mean dosage
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1.08 mg daily [at bedtime]) or placebo for 4 weeks, and the
primary outcome measures were total score changes from
baseline on the CAS-P and the CAS-T.
Among the 25 children included in the study, 13 had
comorbid ODD and 6 had comorbid CD. On both the
CAS-P and the CAS-T, no significant difference was found
between risperidone and placebo in the change in total
score, with the 2 groups improving by a similar magnitude
during 4 weeks of treatment. Nonetheless, the authors
highlighted a significant difference in the proportion of
children improving by 30% or more on the CAS-P, with
12 of 12 risperidone-treated subjects achieving this level
of improvement, compared with 10 of 13 placebo-treated
subjects (P < 0.05).
Findling et al11 evaluated the use of risperidone in the
treatment of children and adolescents with a primary
diagnosis of CD with prominent aggressive behaviour. This
was a 10-week RCT in 20 youth (aged 5 to 15 years), and
the primary outcome measure was the RAAPP, a clinician-
completed global rating scale of aggression (scored 1 to
5). Subjects were excluded if they had moderate-to-severe
ADHD or other significant psychiatric comorbidity, or if
they were being treated with psychotropics. The dosage of
risperidone ranged from 0.75 to 1.5 mg daily, administered
in the morning.
While the difference between groups in RAAPP scores at
week 10 was not significant, the mean change in RAAPP
score from baseline to week 10 was significantly greater
in subjects treated with risperidone (–1.65), compared
with placebo (–0.16) (P = 0.03). Significant differences
between the risperidone and placebo groups were also seen
for secondary outcome measures, including the CGI-S and
CGI-I scales, the Conduct Problem subscale of the CPRS,
and the Delinquent Behaviour subscale of the CBCL;
however, the difference in the Aggressive Behaviour
subscale of the CBCL was nonsignificant.
Connor et al12 evaluated the use of quetiapine for the
treatment of CD in a 7-week RCT in 19 adolescents.
Eligible subjects were aged 12 to 17 years and had a
primary psychiatric diagnosis of CD, with moderate-to-
severe aggressive behaviour based on an OAS score of
26 or more and a CGI-S score of 4 or more. Subjects with
significantly subaverage IQ and concurrent administration
of any psychoactive medication were excluded. Participants
were given a single-blind placebo for 1 week, and those no
longer meeting entrance criteria at week 2 (randomization)
were excluded from further participation. Quetiapine
and placebo were administered twice daily, with gradual
titration to a minimal dosage of 200 mg daily and up to
800 mg daily based on clinician-assessed benefits and
patient tolerability. The clinician-rated CGI-S and CGI-I
scales were the primary outcome measures.
Significant differences at baseline between groups included
the age of subjects, which was significantly lower in the
quetiapine group, compared with the placebo group
(13.1 and 15.0 years, respectively), and a history of legal
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In Review
involvement, which was present in 33% of the quetiapine
group and 100% of the placebo group, respectively. Rates
of comorbidity were high in both groups; 95% had ODD
and 79% had ADHD. The mean dosage of quetiapine,
administered twice daily, at study end point was 294  mg
daily (SD 78). CGI-S scores decreased from 5.9 at random-
ization to 3.4 at end point in the quetiapine group, compared
with a decrease from 5.5 to 5.0 with placebo (P = 0.007).
Further, at study end point, 8 of 9 subjects randomized to
quetiapine were judged improved (a CGI-I score of 2 or
less), compared with only 1 of 10 subjects randomized
to placebo (P < 0.001). Changes in secondary outcomes,
including the OAS and the CPRS, were not significantly
different between groups, though the study was not
adequately powered for these analyses.
Discussion
An important finding of our review of SGAs for disruptive
behaviour is that 4 placebo-controlled studies support
the short-term (that is, 10 weeks or less) efficacy of
low-dosage risperidone (about 1 mg daily in 3 of the 4
studies) in youth with subaverage IQs. However, placebo-
controlled evidence is limited for adolescents as only 2 of
the 4 studies included youth aged 13 years and older, and
both of these were small.6,8 One maintenance study of low-
dosage risperidone in youth aged 5 to 17 years supported
its efficacy during a 6-month period, but even so, close to
60% of subjects randomized to placebo did not experience
recurrence of symptoms.9 The latter result suggests that
even when patients do well with risperidone, tapering the
medication is reasonable after several months of stability,
especially if adverse effects become problematic.
Our review also found that placebo-controlled evidence is
weak or nonexistent for SGAs, other than risperidone, and
it is weak in youth with average IQs. In fact, only 3 small
studies in youth with average IQs and disruptive behaviour
have been published, totalling 64 subjects. The study by
Armenteros et al10 with risperidone was negative on both
primary outcome measures, the one by Findling et al11 with
risperidone was positive on most but not all primary and
secondary outcome measures, and the one by Connor et al12
with quetiapine was positive on both primary outcome
measures but only 1 of 3 secondary measures. Note, in
the Armenteros et al study10 all subjects had ADHD and
were on a constant dose of a psychostimulant, whereas the
Findling et al study11 excluded subjects who had moderate-
to-severe ADHD or were taking another psychotropic,
and the Connor et al study12 also excluded subjects taking
another psychotropic, even though 79% of included
subjects had ADHD. Thus, regarding the common practice
of augmenting a psychostimulant with an SGA to target
aggression associated with ADHD, placebo-controlled
evidence is extremely limited and the evidence that exists
is essentially negative. In contrast, multiple placebo-
controlled and other rigorously designed studies support the
use of psychostimulants alone to treat aggression associated
with ADHD, particularly when psychostimulant treatment
726 W La Revue canadienne de psychiatrie, vol 57, no 12, décembre 2012
is carefully monitored and adjusted (for example, different
dosages and formulations are tried) and is combined with
behavioural therapy.14–16
The evidence regarding the efficacy of SGAs for disruptive
behaviour in youth, especially in those with average IQs, is
highly incongruous with pediatric prescribing patterns for
these agents in North America during the past 2 decades.
Between 1995–1996 and 2001–2002, the frequency of
antipsychotic prescribing for American youth was found
to increase from 8.6 to 39.4 per 1000.17 In almost 30%
of youth, the diagnosis was ADHD or CD, whereas less
than 8% had a pervasive developmental disorder or an
intellectual disability. Similar results were found in another
American study2 during roughly the same time period, and
in this report, 90% or more of antipsychotic prescriptions
were for an SGA. More recent data reveal that American
prescription rates of SGAs continued to increase in youth
through 2006,18 and doubled in preschoolers (aged 2 to 5
years) from 1999 to 2007.19 While pediatric prescriptions of
antipsychotics are still less frequent in Canada, compared
with the United States, the pattern of increasing use is
similar. Between 1999 and 2008, the rate of antipsychotic
use in Manitoba youth increased from 1.9 to 7.4 per
1000, despite a sharp decline in prescriptions for first-
generation antipsychotics.20 In addition, antipsychotic
recommendations for youth across Canada were found to
increase by 114% from 2005 to 2009, by which point 95% of
the recommendations were for an SGA.1 In both Canadian
studies, the most common indication for the antipsychotic
was ADHD, with CD ranking second or third.
Given the growing evidence regarding weight gain,
metabolic abnormalities, and other adverse effects
associated with SGAs, considerable concern has been
raised about the increasing use of these agents in
children and adolescents.5,21,22 However, what appears
to be underappreciated is the paucity of data supporting
the efficacy of SGAs for disruptive behaviour in youth
with average IQs, even though this is the most common
clinical situation in which SGAs are prescribed. Multiple
factors likely account for the disconnect between the
evidence and clinical practice, including extrapolation from
studies in youth with autism or subaverage IQs7,13,23; ease
of SGA titration and the mistaken perception that little
monitoring is required24,25; unavailability of psychosocial
treatment alternatives26; limited familiarity or comfort
with other pharmacological options (for example,
psychostimulants, antidepressants, alpha-agonists, lithium,
and anticonvulsants); clinical and cultural norms; and the
influence of the pharmaceutical industry.27,28
Limitations of our review relate mainly to the nature of
the available literature: the number of published studies is
modest; sample sizes are generally small (particularly for
youth with average IQs and for adolescents); the quality of
most studies is only fair (online eAppendix 2); unpublished
data are not readily available, and therefore could not be
reviewed; and all published studies were funded by drug
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 Second-Generation Antipsychotics for the Treatment of Disruptive Behaviour Disorders in Children: A Systematic Review
companies. These limitations along with our findings
highlight the need for further research that is nonindustry-
funded and includes the kinds of patients that are most
frequently treated with SGAs. An urgent need also exists
for increased medical education and community resources
that promote evidence-based treatment for disruptive and
aggressive youth, especially the provision of appropriate
psychosocial interventions.29,30
Acknowledgements
The authors acknowledge Miss Lundy Day for her assistance
with formatting the manuscript.
Dr Pringsheim has received consultation and speaking fees
from Shire Canada. Dr Gorman has nothing to disclose.
The Canadian Psychiatric Association proudly supports the
In Review series by providing an honorarium to the authors.
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