Anda di halaman 1dari 13

See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/6598683

The Influence of Risperidone on Attentional Functions in Children and


Adolescents with Attention-Deficit/Hyperactivity Disorder and Co-Morbid
Disruptive Behavior Disorder

Article  in  Journal of Child and Adolescent Psychopharmacology · January 2007


DOI: 10.1089/cap.2006.16.725 · Source: PubMed

CITATIONS READS

19 52

4 authors:

Thomas Günther Beate Herpertz-Dahlmann


RWTH Aachen University RWTH Aachen University
73 PUBLICATIONS   554 CITATIONS    448 PUBLICATIONS   10,571 CITATIONS   

SEE PROFILE SEE PROFILE

Jelle Jolles Kerstin Konrad


Vrije Universiteit Amsterdam RWTH Aachen University
715 PUBLICATIONS   29,308 CITATIONS    240 PUBLICATIONS   6,402 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Dysphagie im Erwachsenenalter View project

SAM - 'Study of Attention Deficit Mastricht' View project

All content following this page was uploaded by Jelle Jolles on 11 August 2015.

The user has requested enhancement of the downloaded file.


14366C09.pgs 12/18/06 11:44 AM Page 725

JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY


Volume 16, Number 6, 2006
Mary Ann Liebert, Inc.
Pp. 725–735

The Influence of Risperidone on Attentional


Functions in Children and Adolescents with
Attention-Deficit/Hyperactivity Disorder and
Co-Morbid Disruptive Behavior Disorder

Thomas Günther, Ph.D.,1 Beate Herpertz-Dahlmann, M.D.,1 Jellemer Jolles, Ph.D.,2


and Kerstin Konrad, Ph.D.1

ABSTRACT

This study aims to examine the influence of risperidone on various attentional functions, in-
cluding intensity and selectivity aspects of attention plus inhibitory control in children with
attention deficit/hyperactivity disorder (ADHD) with co-morbid Disruptive Behavior Disor-
ders (DBD) and normal IQ. Children with ADHD and DBD, aged 8–15 years, were treated
with risperidone (mean daily dose: 1.5 mg; n = 23) and examined with three attentional para-
digms before and after a 4-week treatment period. Age- and IQ-matched normal controls (n =
23) were also tested without medication on the same two occasions. No influence of the med-
ication could be detected for any neuropsychological variable, neither as a positive enhance-
ment nor as adverse side effects. However, clinical symptoms of ADHD and DBD assessed
on the IOWA Conners Scale significantly improved after the 4-week treatment period. Diver-
gent behavioral and cognitive effects of risperidone on ADHD symptoms were observed,
with a significant reduction in behavioral symptoms, whereas no positive treatment effects
were found on laboratory tasks of impulsivity. Thus, the cognitive effects of risperidone
seem to differ from the cognitive effects of stimulant treatments in children with ADHD +
DBD. However, no negative impact of risperidone was observed on attentional functions ei-
ther, i.e., there was no slowing of cognitive speed.

INTRODUCTION (Schreier 1998; Frazier et al. 1999), pervasive


developmental disorder (Barnard et al. 2002;

R ISPERIDONE IS AN ATYPICAL NEUROLEPTIC agent


with combined serotonin and dopamine
antagonism (Leysen et al. 1992). In child and
McCracken et al. 2002; King et al. 2003), tic dis-
orders and obsessive-compulsive disorder (Sc-
ahill et al. 2003; Gilbert et al. 2004), and
adolescent psychiatry, risperidone is success- disruptive behavior disorders (Barch et al.
fully used to treat neuropsychiatric disorders 2003; Aman et al. 2004; Aman et al. 2005a). Ag-
like schizophrenia (Grcevich et al. 1996; Ar- gression is a common target symptom for
menteros et al. 1997), bipolar disorder which antipsychotics are prescribed to youths

1Department of Child and Adolescent Psychiatry, Aachen University, Aachen, Germany.


2Maastricht Brain & Behaviour Institute and Department of Psychiatry & Neuropsychology, Maastricht University,

725
14366C09.pgs 12/18/06 11:44 AM Page 726

726 GÜNTHER ET AL.

seen in psychiatric clinics (Kaplan et al. 1994; sedative and amnestic effects of neuroleptic
Turgay 2004), with the best evidence for the ef- drugs generally occur after the first adminis-
ficacy of risperidone treatment for aggression tration, with children seeming to be much
existing for autism (Arnold et al. 2003; McClel- more vulnerable than adults to adverse effects,
lan and Werry 2003; Shea et al. 2004; Aman including sedation (Cheng-Shannon et al.
et al. 2005b) and Disruptive Behavior Dis- 2004; McConville and Sorter 2004; Eapen and
orders (DBD; Turgay 2004). For example, the Gururaj 2005).
use of risperidone has been suggested in the Most evidence on how risperidone influ-
treatment of aggressive behavior in children ences cognitive function comes from studies
with attention-deficit/hyperactivity disorder with healthy adults (Allain et al. 2002; Barrett
(ADHD) plus co-morbid severe DBD (Turgay et al. 2004) and schizophrenic patients. Results
2005). The DBD of the Diagnostic and Statistical are mixed with either cognitive improvement
Manual of Mental Disorders, 4th edition (DSM- (Keefe et al. 1999) or no effect on cognitive
IV) (American Psychiatric Association, 1994) is functions for patients with schizophrenia (Liu
made up of Oppositional Defiant Disorder et al. 2000), whereby the neurochemical basis
(ODD), Conduct Disorder (CD), and DBD-not of these effects is poorly understood. Two
otherwise specified (American Psychiatric As- studies on children with disruptive behavior
sociation 1994). This paper will use the term aged between 5 and 12 years and either bor-
‘DBD’ to refer collectively to CD and ODD. derline intellectual function or mild or moder-
Stimulants are the treatment of first choice ate mental retardation (IQ between 36 and 84)
for ADHD plus co-morbid DBD (Greenhill et found neither evidence for any improvement
al. 2002), but risperidone has a place in the nor for any deterioration of cognitive vari-
management of children with ADHD plus se- ables, such as sustained attention and verbal
vere DBD if other treatments have proven un- learning (Continuous Performance Test & Cal-
successful (Kewley 1999; Morant et al. 2001; ifornia Verbal Learning Test) while partici-
Simeon et al. 2002; Turgay 2005). Several stud- pants were being treated with risperidone
ies have shown that risperidone is associated (Snyder et al. 2002; Turgay et al. 2002). How-
with significant behavioral improvement in a ever, other studies have reported sedative ef-
high percentage of this difficult-to-treat popu- fects in adolescents with schizophrenia
lation (Buitelaar 2000; Findling et al. 2000; (Grcevich et al. 1996) and children with bipolar
Buitelaar et al. 2001; Cesena et al. 2002; Aman disorders and co-morbid ADHD (Schreier
et al. 2002; Aman et al. 2004). Recently, Correia 1998). Most of the available studies with
Filho et al. (2005) demonstrated that risperi- risperidone are case reports, small-open label
done is associated with even greater reduc- studies, and the samples are often inhomoge-
tions in the ADHD total score in children with neous (for review, see Findling and McNamara
moderate mental retardation and ADHD than 2004). Studies with greater clinical samples are
methylphenidate. In clinical terms, children available for tic disorders. Comparative stud-
with ADHD and DBD also seem to benefit ies with risperidone and pimozide (Brugge-
from a combined treatment of stimulants and man et al. 2001) or risperidone and clonidine
risperidone. According to Turgay et al. (2002), (Gaffney et al. 2002) again reported sedation,
the efficacy of risperidone is not affected by somnolence, and fatigue as side effects for
type of disorder, level of retardation, pres- risperidone.
ence/absence of ADHD, or use of stimulants. Thus, risperidone is an important pharma-
The most common side effects in risperi- cological agent in the treatment of children
done-treated patients are weight gain, extra- with ADHD plus associated severe DBD when
pyramidal symptoms, somnolence, sedation, other treatments have proven unsuccessful.
headache, dyspepsia, enuresis, rhinitis, vomit- Although no negative influences on cognitive
ing, and increased prolactin elevation (Buite- functions have been demonstrated for DBD
laar et al. 2001; Aman et al. 2002; Cesena et al. children with subaverage IQ (Snyder et al.
2002; Snyder et al. 2002; Aman et al. 2004; 2002; Turgay et al. 2002), little is known about
Aman et al. 2005b; Hellings et al. 2005). The cognitive side effects in ADHD + DBD chil-
14366C09.pgs 12/18/06 11:44 AM Page 727

INFLUENCE OF RISPERIDONE ON ATTENTION 727

dren with average IQ. This is why our study TABLE 1. BASELINE CHARACTERISTICS OF THE PARTICIPANTS
IN THE STUDY
aimed to examine the influence of risperidone
on various attentional systems in a sample of Controls ADHD + DBD Group
ADHD + DBD children with average IQ who (n = 23) (n = 23) difference
had not benefited sufficiently from previous
stimulant treatment alone. Because sedation is Age (mean ± SD) 11.9 ± 2.2 11.9 ± 2.1 NS
IQ (mean ± SD) 96.9 ± 10.9 92.8 ± 12.3 NS
an adverse event that is frequently associated Sex (male/female) 18/5 21/2 NS
with risperidone treatment, we expected atten-
tional functions to decline due to the sedative NS = not significant.
effects of this atypical neuroleptic agent.
Current concepts of attention generally dis- the diagnostic criteria for ODD whereas 10
tinguish between the selectivity and intensity children had co-morbid CD (American Psychi-
of attention (Van Zomeren and Brouwer 1994). atric Association 1994). Table 1 summarizes
Selectivity refers to the process that modulates the baseline characteristics of the samples.
responsiveness to specific stimuli constella- Prior to the study, all children underwent an
tions by giving priority to certain stimuli, extensive psychiatric examination conducted
whereas intensity describes the ability to by an experienced child psychiatrist. A further
activate and maintain attention over time. In psychiatric classification was then determined
addition to the selectivity and intensity com- on the basis of a German semistructured inter-
ponents of attention, a supervisory attentional view with the parents and the child (K-DIPS;
system (SAS) is assumed to act as a control Unnewehr et al. 1995) performed by a second
mechanism to modulate the two dimensions independent rater who was blind to the first
of selectivity and intensity. On the basis of pre- rater’s diagnosis.
vious studies, we assumed that children with Exclusion criteria were general IQ below 80
ADHD + DBD had deficits within the SAS as (WISC-III) and any kind of neuroleptic med-
reflected by higher cognitive impulsivity (for ication prior to the study. In addition to the
review, see Sergeant 2005), but also showed ADHD + DBD diagnosis, the co-morbid disor-
deficits in the intensity aspects of attention (for ders were dysthymic disorder (n = 1; DSM-IV:
review, see Huang Pollock and Nigg 2003) 300.4), major depression with a recent episode
when compared to normal controls before of minor severity (n = 2; DSM-IV: 296.21), and
risperidone treatment. Due to the sedative anxiety disorders (social phobia [n = 3; DSM-
effect of risperidone, we also expected it to IV: 300.23], separation anxiety disorder [n = 2;
have a negative impact on the intensity aspect 309.21]) in the clinical group. Of the 23 pa-
of attention. However, we assumed that both tients, 21 subjects were males and 2 females.
aggressive behavior and a cognitive impulsiv- All of the patient children had the following
ity task would improve during risperidone characteristics in common: Attentional prob-
treatment. lems, hyperactive-impulsive symptoms, and a
repetitive and persistent pattern of socially
dysfunctional, aggressive, or defiant behavior
that was sufficiently severe to disturb their
METHOD
schooling and everyday life.
The control group (NC) was recruited from
Participants and selection procedure
elementary schools and junior–senior high
A total of 23 children with a lifetime diagno- schools. Only Caucasian participants were in-
sis of ADHD plus DBD and 23 healthy con- cluded in the study, and school education of
trols, all aged 8–15 years, participated in this the participants and socioeconomic status
study. In the clinical sample, 18 children met (Moore and Kleining, 1968), evaluated accord-
the DSM-IV criteria for ADHD and 5 adoles- ing to the paternal profession, did not differ
cents had a lifetime diagnosis of ADHD, but between both groups.
currently only fulfilled the ADHD criteria in The 23 children were matched to the ADHD
partial remission. In addition, 13 children met + DBD group on age and IQ. The 23 partici-
14366C09.pgs 12/18/06 11:44 AM Page 728

728 GÜNTHER ET AL.

pants in the NC group (18 male, 5 females) had 5 days of in-patient treatment to control for the
no history of psychiatric diagnosis. The two efficacy of the treatment. The rating scale was
groups were not different with respect to sex filled out by specialized staff members. If the
distribution (2(1) = 1.52; p = NS), age (t(44) = children received also stimulants, these were
0.06; p = NS) or IQ (t(54) = 1.19; p = NS). In- discontinued 48 hours before the neuropsy-
formed parental and patient consent was ob- chological examinations and before the 5-day-
tained for all participants. interval of behavioral ratings at both times of
measurement, T1 and T2. This procedure was
chosen to ensure that the dependent variables
Medication log
were not influenced by the stimulant treat-
The ADHD + DBD group was recruited ment of the children.
from our in-patient ward at the Department of
Child and Adolescent Psychiatry. All children
Outcome measures
showed severe aggressive behavior and had a
long history of disruptive and impulsive be- All subjects received a standardized com-
havior in various social settings. They received puterized neuropsychological assessment be-
risperidone in addition to a standardized cog- fore treatment with risperidone (T1) and again
nitive behavioral treatment program, includ- 4 weeks after treatment onset with risperidone
ing parental education and single and peer (T2). The dose of the risperidone medication
group therapy. The treatment program incor- was kept stable over 2 weeks before T2. To
porated training in problem solving, anger control for retest effects, the normal controls
management, and interpersonal skills and was were also tested twice without medication at
continued during the study. In addition, be- the start and at the end of the 4-week test
havioral techniques, such as token economy period. The order of the neuropsychological
systems, and time-out procedures, were used tests was randomized. Attentional functions
to increase desirable behavior and decrease were assessed by the following computerized
undesirable behavior. tests in accordance with Van Zomeren and
Risperidone was started at 0.25 mg/day and Brouwer’s framework of attention (1994).
increased until a positive clinical response was Intensity of Attention: The Sustained Atten-
obtained or side effects emerged. The daily tion Task involved the continuous and consec-
dose varied between 1 mg and 2.5 mg [mean utive presentation of 50 series of 12 different
dose = 1.5 mg; standard deviation (SD) = 0.5] dot patterns (600 signals; de Sonneville 2000).
and was between 0.03 mg and 0.04 mg/kg per In each series, an equal number of 3-, 4-, or 5-
day. 18 children with ADHD + DBD were dot patterns was presented in pseudo-random
treated with a combination of risperidone and order. The child was instructed to push the
stimulants [methylphenidate (n = 7), methyl- ‘yes’ button with the dominant hand when-
phenidate HCl (n = 9), and D-amphetamine (n ever a 4-dot pattern (target) was shown and to
= 2)]. The stimulant medication did not change press the ‘no’ button with the nondominant
during the study, and the duration of the med- hand when the pattern contained 3 or 5 dots
ication before the study varied between 8 (nontargets).
weeks and 7 years. In addition, 5 adolescents Selectivity of Attention: Divided Attention
diagnosed with ADHD in partial remission was a dual task that combined a visual and
and CD were given a monotherapy with acoustic discrimination task (Fimm and Zim-
risperidone. The risperidone medication was mermann 2001). Children were asked to re-
not discontinued in any of these patients dur- spond as quickly as they could whenever a
ing the period of the study and no other drugs square appeared and if an alternating high and
[e.g., (SSRIs), anticonvulsants, etc.] were used deep tone was repeated. One hundred stimuli
before, during, or after the study. The score on were presented containing 17 visual and 16
the IOWA Conners rating scale (Pelham et al. acoustic goal targets.
1989; Collett et al. 2003) was averaged across 5 SAS: In the Go/No-Go Paradigm (Fimm
days before risperidone treatment and the last and Zimmermann 2001) that assesses response
14366C09.pgs 12/18/06 11:44 AM Page 729

INFLUENCE OF RISPERIDONE ON ATTENTION 729

selection/inhibition, a motor response with TABLE 2. IMPROVEMENT ON THE IOWA CONNERS RATING
the dominant hand was either initiated (go) or SCALE FOR THE RISPERIDONE GROUP (n = 23)
inhibited (no-go) depending on whether an T1a T2b
“x” (go) or a “+” (no-go) stimulus appeared. M (SD) M (SD) Group difference
Visual stimuli appeared in random order for
200 msec with a variable intertrial interval of a IOWAc 11.2 (4.5) 8.4 (2.9) p = 0.008
IOd 5.9 (2.7) 4.3 (1.9) p = 0.023
maximum of 1,600 msec. Half (50%) of the 40 AGe 5.4 (2.7) 4.1 (1.5) p = 0.039
stimuli were go trials. The design of this task
triggers impulsive reactions (false alarms) and SD = standard deviation; IO = Inattention-Overactiv-
ity; AG = Aggression; M = mean.
the number of false alarms is a good measure- aAssessment before treatment.
ment for impulsive behavior (Van Zomeren bAssessment 4 weeks after treatment onset.

and Brouwer 1994). cIOWA Conners rating scale sum score.


dInattention-Overactivity (IO).
The dependent measures in all three tasks eAggression (AG).
were reaction time (RT) and its SD, the number
of misses (MIS), and false alarms (FA).
In addition to the neuropsychological exam- 0.003). Significant improvement was found for
ination, behavioral changes were also assessed both subscales of the IOWA Conners scale (IO
by the IOWA Conners rating scale (Pelham et and AG: (t(22) > 2.2; p < 0.039). For more details
al. 1989; Collett et al. 2003) filled out by trained see Table 2.
staff on the inpatient wards. The IOWA Con-
ners rating scale contains two subscales, Inat-
Intensity of Attention: Sustained Attention
tention-Overactivity (IO) and Aggression
Task
(AG), each of which consists of five items.
No group difference was found between NC
and ADHD + DBD at T1 and T2 as far as speed
Data analysis
(F(1/44) = 0.9; nsec) and number of FA (F(1/44) =
Data were analyzed using SPSS 12 (SPSS 0.97; NS) were concerned. However, both
Inc., 2003). The demographic characteristics groups performed significantly better on these
were assessed by an independent t-test (IQ two variables at T2 (F(1/44) > 10.28; p < 0.003).
and age) and 2-Pearson (sex distribution). By contrast, speed fluctuation (F(1/44) = 2.95;
Changes to the IOWA score within the risperi- NS) and number of MIS (F(1/44) = 0.06; NS) did
done group were analyzed with a paired sam- not change over time. However, children with
ple t-test. Repeated measure group differences ADHD + DBD had a significantly higher
were evaluated using repeated measure analy- speed fluctuation (F(1/44) = 9.24; p = 0.004) and
sis of variance (ANOVAR), with the diagnostic made a higher number of MIS (F(1/44) = 5.51; p
group as the independent variable, time of = 0.024) than the NC group. No significant
measurement as the within-subject factor, and group  time interaction was observed, indi-
neuropsychological test scores as the depen- cating no significant impact of the risperidone
dent variables. It was decided not to adjust for medication on any of the dependent measures
multiple testing to avoid Type II errors and to for the sustained attention task (F(1/44) < 1.81;
enhance sensitivity for detecting even milder NS). For details see Table 3.
cognitive side effects (Tabachnick and Fidell
2000). All tests were two-tailed.
Selectivity of Attention:
Divided Attention Task
RESULTS No difference could be detected between
NC and ADHD + DBD (F(1/44) < 0.63; NS) in
As expected, the total score on the IOWA any of the variables. The results of RT and its
Conners scale for the ADHD + DBD group de- SD did not change significantly at T2 (F(1/44) <
creased significantly from T1 to T2 (T1: M = 3.16; NS), whereas both error rates, FA (F(1/44) =
11.2 (±4.5), T2 = 8.4 (±2.9), t(22) = 3.34; p = 7.4; p = 0.009) as well as the number of MIS
14366C09.pgs

730
12/18/06
11:44 AM

TABLE 3. NEUROPSYCHOLOGICAL PERFORMANCE OF THE CONTROL GROUP AND RISPERIDONE GROUP, SHOWN SEPARATELY FOR TIME OF ASSESSMENT
Controls Risperidone
(n = 23) (n = 23) Between- Within- Interaction
M (SD)a M (SD) a subject effect subject effect (group  time)
Page 730

T1b T2c T1b T2c F (p) F (p) F (p)

Sustained attention
Speed (seconds) 13.7 (3.9) 11.7 (3.4) 14.1 (4.2) 13.3 (4.4) 0.90 (NS) 10.28 (p = 0.003) 1.81 (NS)
Speed fluctuation (seconds) 2.5 (1.3) 2.1 (1.3) 3.7 (1.8) 3.3 (1.5) 9.24 (p = 0.004) 2.95 (NS) 0.1 (NS)
False alarms 21.7 (14.6) 13.7 (8.7) 24.3 (18.3) 18.8 (16.7) 0.97 (NS) 10.70 (p = 0.002) 0.34 (NS)
Misses 27.7 (18.1) 31.5 (21.5) 47.1 (33.1) 44.8 (29.3) 5.51 (p = 0.024) 0.06 (NS) 0.87 (NS)
Divided Attention
Reaction time (msec) 757 (119) 747 (115) 809 (260) 726 (91) 0.16 (NS) 2.86 (NS) 1.75 (NS)
Standard deviation (msec) 294 (95) 283 (75) 318 (115) 267 (83) 0.04 (NS) 3.16 (NS) 1.36 (NS)
False alarms 4.4 (4.5) 2.8 (3.9) 3.8 (4.6) 1.9 (1.7) 0.63 (NS) 7.4 (p = 0.009) 0.04 (NS)
Misses 6 (4.8) 4.8 (5.3) 5.9 (4.2) 4 (3.3) 0.12 (NS) 8.15 (p = 0.007) 0.39 (NS)
Go/No-Go
Reaction time (msec) 431 (81) 445 (67) 454 (120) 437 (105) 0.08 (NS) 0.02 (NS) 1.81 (NS)
Standard deviation (msec) 112 (46) 113 (39) 120 (37) 127 (49) 0.84 (NS) 0.56 (NS) 0.30 (NS)
False alarms 3 (2.8) 3.1 (2.7) 6.2 (4.6) 5.6 (4) 10.01 (p = 0.003) 0.18 (NS) 0.52 (NS)
Misses 1 (1.1) 0.7 (1) 2 (2.5) 0.9 (1.6) 2.74 (NS) 5.58 (p = 0.023) 0.93 (NS)

SD = standard deviation; NS = not significant.


aMean (standard deviation).
bAssessment before treatment.
cAssessment 4 weeks after treatment onset.
GÜNTHER ET AL.
14366C09.pgs 12/18/06 11:44 AM Page 731

INFLUENCE OF RISPERIDONE ON ATTENTION 731

(F(1/44) = 8.15; p = 0.007) decreased. No signifi- detected in all parts of the sustained attention
cant influence of the risperidone medication task due to the repetition of the tasks. How-
was detected for any of the divided attention ever, contrary to our hypotheses, no differen-
variables (F(1/44) < 1.75; NS). tial influence of the risperidone medication
could be detected on the neuropsychological
task variables, neither as a positive enhance-
SAS: Go/No-Go-Paradigm
ment nor as an adverse side effect.
No within (F(1/44) < 0.56; NS) or between The decrease in aggression and inattention-
subject effect (F(1/44) < 0.84; NS) could be de- overactivity behavior scales under risperidone
tected for the RTs and the within-subject vari- treatment in our sample is consistent with an
ability of RTs. The number of MIS was emerging body of literature in pediatric psy-
comparable for both groups (F(1/44) = 2.74; NS), chopharmacology documenting the effective-
whereas the number of FA, a measure of im- ness of risperidone in the treatment of ADHD
pulsivity, was significantly higher in the and/or aggression in children and adolescents
ADHD + DBD group (F(1/44) = 10.01; p = 0.003). (e.g., Buitelaar et al. 2001; Findling and McNa-
Furthermore, all children made fewer MIS at mara 2004). However, in addition to the phar-
T2 (F(1/44) = 5.58; p = 0.023). Again, no signifi- macotherapy, ADHD + DBD children received
cant influence of the risperidone medication a cognitive-behavioral treatment program.
was detected for any of the Go/No-Go vari- Furthermore, our study was an open clinical
ables (F(1/44) < 1.81; NS). trial, which meant that Rosenthal’s “expecta-
tion effect” could not be ruled out (Goodwin
1998). Thus, the improvement in the behavior
DISCUSSION scales could not be solely interpreted in the
light of risperidone treatment. In addition, be-
Our goal was to examine the influence of the havioral improvement might interact with
neuroleptic agent risperidone on various at- neuropsychological measures used in this
tentional functions, including intensity of at- study. Note, however, that our study found
tention, selectivity of attention, and inhibitory equal behavioral improvement for both sub-
control in children with ADHD and co-morbid scales of the IOWA Conners rating scale, al-
DBD with normal intelligence. We expected a though it has been demonstrated that
negative impact on the intensity aspect of at- cognitive-behavioral therapy is less effective
tention but an improvement in the impulsivity in reducing overactive and inattentive behav-
related task. Previous research did not focus ior than aggressive symptoms (Pelham et al.
on the cognitive adverse effects of risperidone 1998; Kutcher et al. 2004). So, it seems to be un-
or were based either on adults or included likely at least that the behavioral improvement
only children with ADHD + DBD with subav- observed is primarily due to the cognitive be-
erage IQ. In agreement with previous research, havioral treatment procedure.
we found that unmedicated children with Sedation could be a troublesome side effect
ADHD + DBD showed intensity deficits of at- (Buitelaar 2000; Eapen and Gururaj 2005), and
tention and were more impulsive in laboratory we assumed that sedation may particularly af-
tasks than normal controls (e.g., Halperin et al. fect performance in a computerized sustained
1990; Lynam 1996; Oosterlaan et al. 1998; Oost- attention task. It was hypothesized that the
erlaan and Sergeant 1998; Hill 2002; Nigg 2003; sedative effect of risperidone might cause a
van Goozen et al. 2004). Note, however, that cognitive slowing in this attentional task.
dependent variables were interpreted accord- However, no negative influence of the risperi-
ing to Van Zomeren and Brouwer’s framework done medication could be detected in our
of attention (1994), linking deficits in the sus- study. Nevertheless, the results are in agree-
tained attention task primarily to intensity ment with previous research on children with
functions of attention and false alarms in the subaverage IQ, demonstrating that cognitive
Go/No-Go Task to cognitive impulsivity. Fur- functions were not affected by risperidone
thermore, fewer errors and greater speed were treatment (Snyder et al. 2002; Turgay et al.
14366C09.pgs 12/18/06 11:44 AM Page 732

732 GÜNTHER ET AL.

2002). The sedative and amnestic effects of tion of risperidone to a psychostimulant treat-
psychotropic drugs occurred mainly after the ment resulted in significantly better control of
first administrations (Barrett et al. 2004). In ad- hyperactivity than was achieved with stimu-
dition, the doses of risperidone prescribed for lant treatment alone, without causing any in-
children with DBD are much lower than those crease in adverse events. However, to examine
typically administered to schizophrenic pa- the differential effects of stimulants and
tients who had been included in the majority risperidone in children with ADHD and DBD,
of studies. It is also possible that the sedative comparative studies with either stimulants
effects of risperidone might disappear after a and risperidone or treatment with risperidone
few weeks (Aman et al. 2002) or that the dura- alone are needed.
tion of the neuropsychological testing was too In conclusion, the present study found that
short to assess sedation effects. However, in risperidone did not affect attention in children
summary and in agreement with previous re- with ADHD + DBD and normal IQ. This inter-
search (e.g., Frazier et al. 1999; Findling et al. esting finding suggests that risperidone does
2000; Aman et al. 2002), our data demonstrate not decrease attentional functions in children
that the efficacy of risperidone in treating ag- with ADHD + DBD with average intelligence
gressive behavior in children was not due to at dosages below 2.5 mg. However, like all an-
the sedative effect of antipsychotics as had tipsychotics, risperidone should be used with
been hypothesized by other authors (e.g., caution, and any risks associated with the use
Campbell et al. 1992). of risperidone need to be carefully weighed up
Furthermore, no changes were found to the against the poor prognosis of the untreated
supervisory attentional system and selectivity disruptive behavior disorder.
of attention during risperidone treatment. This
is in line with a recent study by Snyder et al.
(2002) and Turgay et al. (2002). In their study DISCLOSURES
of more than 100 children with subaverage IQ,
no deterioration of Verbal Learning Test and Drs. Günther, Herpertz-Dahlmann, Jolles,
Continous Performance Test abilities could be and Konrad have no financial ties or conflicts
detected during risperidone treatment. of interest to report.
Taken together, risperidone seems to be use-
ful in treating impulsivity and aggression in
children and adolescents with ADHD + DBD REFERENCES
and average IQ, and we did not find any nega-
tive impact on attentional functions. However, Allain H, Tessier C, Bentué Ferrer D, Tarral A, Le
more importantly, although risperidone re- Brenton S, Gandon JM, Bouhours P: Effects of
duces ADHD symptoms in behavioral terms risperidone on psychometric and cognitive func-
(see also Correia Filho et al. 2005), it does not tions in healthy elderly volunteers. Psychophar-
macology (Berl). 165:419–429, 2002.
show the same positive cognitive effects as Aman MG, De Smedt G, Derivan A, Lyons B, Find-
produced by stimulants. Stimulants have been ling RL: Risperidone disruptive behavior study
demonstrated to reduce significantly deficits group: Double-blind, placebo-controlled study of
in vigilance, within-subject variability, and im- risperidone for the treatment of disruptive be-
pulsivity in laboratory tasks (e.g., Scheres et al. haviors in children with subaverage intelligence.
Am J Psychiatry 159:1337–1346, 2002.
2003; Konrad et al. 2004). So, our results indi- Aman MG, Binder C, Turgay A: Risperidone effects
cate that the behavioral and cognitive effects in the presence/absence of psychostimulant
of risperidone might be even more divergent medicine in children with ADHD, other disrup-
than has been previously described for stimu- tive behavior disorders, and subaverage IQ. J
lants in ADHD (e.g., Solanto 2002). Additional Child Adolesc Psychopharmacol. 14:243–254,
stimulant treatment might be useful to treat 2004.
Aman M, Buitelaar J, De Smedt G, Wapenaar R,
the core attentional deficits in children with Binder C: Pharmacotherapy of disruptive behav-
ADHD + DBD. In line with this, Aman and ior and item changes on a standardized rating
collegues (2004) demonstrated that the addi- scale: Pooled analysis of risperidone effects in
14366C09.pgs 12/18/06 11:44 AM Page 733

INFLUENCE OF RISPERIDONE ON ATTENTION 733

children with subaverage IQ. J Child Adolesc Cesena M, Gonzalez Heydrich J, Szigethy E,
Psychopharmacol. 15:220–232, 2005a. Kohlenberg TM, DeMaso DR: A case series of
Aman MG, Arnold E, McDougle CJ, Vitiello B, Sc- eight aggressive young children treated with
ahill L, Davies M, McCracken JT, Tierney E, Nash risperidone. J Child Adolesc Psychopharmacol
PL, Posey DJ, Chuang S, Martin A, Shah B, Gon- 12:337–345, 2002.
zalez NM, Swiezy NB, Ritz L, Koenig K, Mc- Cheng-Shannon J, McGough JJ, Pataki C, Mc-
Gough J, Ghuman J, Lindsay RL: Acute Cracken JT: Second-generation antipsychotic
long-term safety and tolerability of risperidone in medications in children and adolescents. J Child
children with autism. J Child Adolesc Psy- Adolesc Psychopharmacol 14:372–394, 2004.
chopharmacol. 15:869–884, 2005b. Collett BR, Ohan JL, Myers KM: Ten-Year Review
American Psychiatric Association: Diagnostic and of Rating Scales. V: Scales asessing attention-
Statistical Manual of Mental Disorders, 4th ed. deficit/hyperactivity disorder. J Am Acad Child
(DSM-IV). Washington, DC, American Psychi- Adolesc Psychiatry 42:1015–1037, 2003.
atric Association, 1994. Correia Filho AG, Bodanese R, Silva TL, Alvares JP,
Armenteros JL, Whitaker AH, Welikson M, Stedge Aman M, Rohde LA: Comparison of risperidone
DJ, Gorman J: Risperidone in adolescents with and methylphenidate for reducing ADHD symp-
schizophrenia: an open pilot study. J Am Acad toms in children and adolescents with moderate
Child Adolesc Psychiatry 36:694–700, 1997. mental retardation. J Am Acad Child Adolesc
Arnold LE, Vitello B, McDougle C, Scahill L, Shah Psychiatry 44:748–755, 2005.
B, Gonzalez NM, Chuang S, Davies M, Hollway de Sonneville LMJ: ANT 2.1—Amsterdam Neu-
J, Aman MG, Cronin P, Koenig K, Kohn AE, ropsychological Tasks. Amstelveen, Sonar, 2000.
McMahon DJ, Tierney E: Parent-defined target Eapen V, Gururaj AK: Risperidone treatment in
symptoms respond to risperidone in RUPP Au- 12 children with developmental disorders and
tism Study: Customer approach to clinical trials. J attention-deficit/hyperactivity disorder. Prim
Am Acad Child Adolesc Psychiatry 42:1443– Care Companion J Clin Psychiatry. 7:221–224,
1450, 2003. 2005.
Barch DM, Sheline YI, Csernansky JG, Snyder AZ: Fimm B, Zimmermann P: Testbatterie zur Auf-
Working memory and prefrontal cortex dysfunc- merksamkeitsüberprüfung (TAP), Version 1.6.
tion: Specificity to schizophrenia compared with Herzogenrath, Psytest, 2001.
major depression. Biol Psychiatry 53:376–384, Findling RL, McNamara NK: Atypical antipsy-
2003. chotics in the treatment of children and adoles-
Barnard L, Young AH, Pearson J, Geddes J, O’Brien cents: clinical applications. J Clin Psychiatry 65
G: A systematic review of the use of atypical an- (Suppl 6):30–44, 2004.
tipsychotics in autism. J Psychopharmacol (Oxf) Findling RL, McNamara NK, Branicky LA,
16:93–101, 2002. Schluchter MD, Lemon ERN, Blumer JL: A dou-
Barrett SL, Bell R, Watson D, King DJ: Effects of ble-blind pilot study of risperidone in the treat-
amisulpride, risperidone and chlorpromazine on ment of conduct disorder. J Am Acad Child
auditory and visual latent inhibition, prepulse in- Adolesc Psychiatry 39:509–516, 2000.
hibition, executive function and eye movements Frazier JA, Meyer MC, Biederman J, Wozniak J,
in healthy volunteers. J Psychopharmacol (Oxf) Wilens TE, Spencer TJ, Kim GS, Shapiro S:
18:156–172, 2004. Risperidone treatment for juvenile bipolar dis-
Bruggeman R, van der Linden C, Buitelaar JK, Ger- order: A Retrospective Chart Review. J Am
icke GS, Hawkridge SM, Temlett JA: Risperidone Acad Child Adolesc Psychiatry 38:960–965,
versus pimozide in Tourettes’s disorder: A com- 1999.
parative double-bind parallel group study. J Clin Gaffney GR, Perry PJ, Lund BC, Bever Stille KA,
Psychiatry 62:50–56, 2001. Arndt S, Kuperman S: Risperidone versus cloni-
Buitelaar JK: Open-label treatment with risperi- dine in the treatment of children and adolescents
done of 26 psychiatrically-hospitalized children with Tourette’s syndrome. J Am Acad Child Ado-
and adolescents with mixed diagnoses and ag- lesc Psychiatry 41:330–336, 2002.
gressive behavior. J Child Adolesc Psychophar- Gilbert DL, Batterson R, Sethuraman G, Sallee FR:
macol 10:19–26, 2000. Tic reduction with risperidone versus pimozide
Buitelaar JK, van der Gaag RJ, Cohen Kettenis P, in a randomized, double-blind, crossover trial. J
Melman CT: A randomized controlled trial of Am Acad Child Adolesc Psychiatry 43:206–214,
risperidone in the treatment of aggression in hos- 2004.
pitalized adolescents with subaverage cognitive Goodwin CJ: Research in Psychology—Methods
abilities. J Clin Psychiatry 62:239–248, 2001. and Design. John Wiley & Sons, Inc. (New York),
Campbell M, Gonzalez NM, Silva RR: The pharma- 1998.
cological treatment of conduct disorders and Grcevich SJ, Findling RL, Rowane WA, Friedman L,
rage outbursts. Psychiatr Clin N Am 15:69–85, Schulz SC: Risperidone in the treatment of chil-
1992. dren and adolescents with schizophrenia: a retro-
14366C09.pgs 12/18/06 11:44 AM Page 734

734 GÜNTHER ET AL.

spective study. J Child Adolesc Psychopharmacol Leysen JE, Janssen PMF, Gommeren W, Wynants J,
6:251–257, 1996. Pauwels PJ, Janssen PAJ: In vitro and in vivo re-
Greenhill LL, Pliszka S, Dulcan MK, Bernet W, ceptor binding and effects on monoamine
Arnold V, Beitchman J, Benson RS, Bukstein O, turnover in rat brain regions of the novel antipsy-
Kinlan J, McClellan J, Rue D, Shaw JA, Stock S, chotic risperidone and ocaperidone. Mol Phar-
American Academy of Child and Adolescent macol 41:494–508, 1992.
Psychiatry: Practice parameters for the use of Liu SK, Chen WJ, Chang CJ, Lin HN: Effects of
stimulant medications in the treatment of chil- atypical neuroleptics on sustained attention
dren, adolescents, and adults. J Am Acad Child deficits in schizophrenia: A trial of risperidone
Adolesc Psychiatry 41:26S-49S, 2002. versus haloperidol. Neuropsychopharmacology
Halperin JM, O’Brien JD, Newcorn JH, Healey JM, 22:311–319, 2000.
Pascualvaca DM, Wolf LE, Young JG: Validation Lynam DR: The early identification of chronic of-
of hyperactive, aggressive, and mixed hyperac- fenders: Who is the fledgling psychopath? Psy-
tive/aggressive childhood disorders: A research chol Bull 120:209–234, 1996.
note. J Child Psychol Psychiatry 31:455–459, 1990. McClellan JM, Werry JS: Evidence-based treat-
Hellings JA, Zarcone JR, Valdovinos MG, Reese ments in child and adolescent psychiatry: An in-
RM, Gaughan E, Schroeder SR: Risperidone-in- ventory. J Am Acad Child Adolesc Psychiatry
duced prolactin elevation in a prospective study 42:1388–1400, 2003.
of children, adolescents, and adults with mental McConville BJ, Sorter MT: Treatment challenges
retardation and pervasive developmental disor- and safety considerations for antpsychotic use in
ders. J Child Adolesc Psychopharmacol 15:885– children and adolescents with psychoses. J Clin
892, 2005. Psychiatry 65:S20–S29, 2004.
Hill J: Biological, psychological and social pro- McCracken JT, McGough J, Shah B, Cronin P, Hong
cesses in the conduct disorders. J Child Psychol D, Aman MG, Arnold LE, Lindsay R, Nash P,
Psychiatry 43:133–164, 2002. Hollway J, McDougle CJ, Posey D, Swiezy N,
Huang Pollock CL, Nigg JT: Searching for the atten- Kohn A, Scahill L, Martin A, Koenig K, Volkmar
tion deficit in attention deficit hyperactivity dis- F, Carroll D, Lancor A, Tierney E, Ghuman J,
order: The case of visuospatial orienting. Clin Gonzalez NM, Grados M, Vitiello B, Ritz L,
Psychol Rev 23:801–830, 2003. Davies M, Robinson J, McMahon D, Research
Kaplan SL, Simms RM, Busner J: Prescribing prac- Units on Pediatric Psychopharmacology Autism
tices of outpatient child psychiatrists. J Am Acad Network: Risperidone in children with autism
Child Adolesc Psychiatry 32:577–581, 1994. and serious behavioral problems. N Engl J Med
Keefe RS, Silva SG, Perkins DO, Lieberman JA: The 347:314–321, 2002.
effects of atypical antipsychotic drugs on neu- Moore H, Kleining G: Das soziale Selbstbild der
rocognitive impairment in schizophrenia: A re- Gesellschaftsschichten in Deutschland. Kölner
view and meta-analysis. Schizophr Bull Zeitschrift für Soziologie und Sozialpsychologie
25:201–222, 1999. 20:86–119, 1968.
Kewley GDFRCP: Risperidone in comorbid ADHD Morant A, Mullas F, Hernandez S, Rosello B: Phar-
and ODD/CD. J Am Acad Child Adolesc Psychi- macological treatment with risperidone in chil-
atry 38:1327–1328, 1999. dren with behavior disorders. Rev Neurol
King B, Zwi K, Nunn K, Longworth J, Dossetor D: 33:1–15, 2001.
Use of risperidone in a paediatric population: An Nigg JT: Response inhibition and disruptive behav-
opservational study. J Paediatr Child Health iors—Toward a multiprocess conception of etio-
39:523–527, 2003. logical heterogeneity for ADHD combined type
Konrad K, Günther T, Hanisch C, Herpertz- and conduct disorder early-onset type. Ann NY
Dahlmann B: Differential effects of methyl- Acad Sci 1008:170–182, 2003.
phenidate on attentional functions in children Oosterlaan J, Sergeant JA: Response inhibition and
with attention deficit/ hyperactivity disorder. J response re-engagement in attention-deficit/hy-
Am Acad Child Adolesc Psychiatry 43:191–198, peractivity disorder, disruptive, anxious and nor-
2004. mal children. Behav Brain Res 94:33–43, 1998.
Kutcher S, Aman M, Brooks SJ, Buitelaar J, van Oosterlaan J, Logan GD, Sergeant JA: Response In-
Daalen E, Fegert J, Findling RL, Fisman S, Green- hibition in AD/HD, CD, comorbid AD/HD+CD,
hill LL, Huss M, Kusumakar V, Pine D, Taylor E, anxious, and control children: A meta-analysis of
Tyano S: International consensus statement on at- studies with the stop task. J Child Psychol Psy-
tention-deficit/hyperactivity disorder (ADHD) chiatry 39:411–425, 1998.
and disruptive behaviour disorders (DBDs): Pelham WE, Milich R, Murphy DA, Murphy H:
Clinical implications and treatment practice sug- Normative data on the IOWA Conners Teacher
gestions. Eur Neuropsychopharmacol 14:11–28, Rating Scale. J Clin Child Psychol 18:259–262,
2004. 1989.
14366C09.pgs 12/18/06 11:44 AM Page 735

INFLUENCE OF RISPERIDONE ON ATTENTION 735

Pelham WE, Wheeler T, Chronis A: Empirically Tabachnick BG, Fidell LS: Using Multivariate Sta-
supported psychosocial treatments for attention tistics. Allyn & Bacon, New York, 2000.
deficit hyperactivity disorder. J Clin Psychol Turgay A: Aggression and disruptive behavior dis-
27:190–205, 1998. orders in children and adolescents. Expert Rev
Scahill L, Leckman JF, Schultz RT, Katsovich L, Neurotherapeut 4:623–632, 2004.
Peterson BS: A placebo-controlled trial of risperi- Turgay A: Treatment of comorbidity in conduct dis-
done in Tourette syndrome. Neurology 60:1130– order with attention-deficit hyperactivity disor-
1135, 2003. der (ADHD). Essential Psychopharmacology
Scheres A, Oosterlaan J, Swanson J, Morein Zamir 6:277–290, 2005.
S, Meiran N, Schut H, Vlasveld L, Sergeant JA: Turgay A, Binder C, Snyder R, Fisman S: Long-term
The effect of methylphenidate of three forms of safety and efficacy of risperidone for the treat-
response inhibition in boys with AD/HD. J Ab- ment of disruptive behavior disorders with sub-
norm Child Psychol 31:105–120, 2003. average IQs. Pediatrics 110:e34, 2002.
Schreier HA: Risperidone for young children with Unnewehr S, Schneider S, Margraf J: Kinder
mood disorders and aggressive behavior. J Child DIPS—Diagnostisches Interview bei psychischen
Adolesc Psychopharmacol 8:49–59, 1998. Störungen im Kindes und Jugendalter. Springer,
Sergeant JA: Modeling attention-deficit/hyperac- Heidelberg, 1995.
tivity disorder: A critical appraisal of the cogni- van Goozen SHM, Cohen Kettenis PT, Snoek H,
tive-energetic model. Biol Psychiatry 57:1248– Matthys W, Swaab-Barneveld H, van Engeland
1255, 2005. H: Executive functioning in children: A compari-
Shea S, Turgay A, Carroll A, Schulz M, Orlik H, son of hospitalised ODD and ODD/ADHD chil-
Smith I, Dunbar F: Risperidone in the treatment dren and normal controls. J Child Psychol
of disruptive behavioral symptoms in children Psychiatry 45:284–292, 2004.
with autistic and other pervasive developmental Van Zomeren AH, Brouwer WJ: Theories and con-
disorders. Pediatrics 114:634–641, 2004. cepts of attention. In: Clinical Neuropsychology
Simeon J, Milin R, Walker S: A retrospective chart of Attention. Edited by Van Zomeren AH,
review of risperidone use in treatment-resistant Brouwer WJ. Oxford University Press, New York,
children and adolescents with psychiatric disor- Oxford, 1994, pp 7–38.
ders. Prog Neuropsychopharmacol Biol Psychia-
try 26:267–275, 2002.
Snyder R, Turgay A, Aman M, Binder C, Fisman S,
Address reprint requests to:
Carroll A: The Risperidone Study Group: Effects Thomas Günther, Ph.D.
of risperidone on conduct and disruptive behav- Department of Child and Adolescent Psychiatry
ior disorders in children with subaverage IQs. J University Hospital Aachen
Am Acad Child Adolesc Psychiatry Neuenhofer Weg 21
41:1026–1036, 2002. D – 52074 Aachen, Germany
Solanto MV: Dopamine dysfunction in AD/HD: in-
tegrating clinical and basic neuroscience re-
search. Behav Brain Res 130:65–71, 2002. E-mail: thomas.guenther2@post.rwth-aachen.de
14366C09.pgs 12/18/06 11:44 AM Page 736

View publication stats