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JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY

Volume 27, Number 5, 2017


ª Mary Ann Liebert, Inc.
Pp. 429–432
DOI: 10.1089/cap.2016.0111

The Possible Effect of Methylphenidate Treatment


on Empathy in Children Diagnosed with Attention-Deficit/
Hyperactivity Disorder, Both With and Without Comorbid
Oppositional Defiant Disorder

Pavel Golubchik, MD1,2 and Abraham Weizman, MD2–4


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Abstract
Objective: To assess the Empathizing Quotient (EQ) of patients diagnosed with attention-deficit/hyperactivity disorder
(ADHD) only or comorbid with oppositional defiant disorder (ODD) and compare the two groups’ responses to methyl-
phenidate (MPH) treatment.
Methods: Fifty-two children (8–18 years) diagnosed with ADHD, 26 of whom were also diagnosed with comorbid ODD
(ADHD/ODD), were treated with MPH for 12 weeks. The level of EQ was assessed with the Children’s version of the
Empathizing Quotient (EQ-C) and the severity of ADHD symptoms with the ADHD Rating Scale (ADHD-RS). Assessments
were done at baseline and at end point.
Results: A significant increase in EQ scores was obtained in both groups following MPH treatment ( p = 0.003 for ADHD/
ODD; p = 0.002 for ADHD). Significant correlation was found in the ADHD group between the changes in ADHD-RS and
those in EQ, following MPH treatment ( p = 0.015), but not in the ADHD/ODD group ( p = 0.48).
Conclusions: A correlation exists between MPH-related improvement in ADHD symptoms and between more empathy in
children with ADHD not comorbid with ODD.

Keywords: attention-deficit/hyperactivity disorder (ADHD), children and adolescents, Empathizing Quotient (EQ), methyl-
phenidate (MPH), oppositional defiant disorder (ODD)

Introduction involved not only in inhibiting prepotent responses (e.g., activation


of the amygdala in response to threatening social stimuli) but also

A ttention-deficit/hyperactivity disorder (ADHD) in


children has been associated with difficulties in social
communication, social behavior, social functioning, and social
in reflecting on the meaning of a salient social stimulus (Rubia et al.
2009). ADHD can result in inappropriate social behavior, which
may be related to poorer social skills and failure to comprehend the
competence related to executive dysfunction and to emotional dys- impact on others of one’s actions.
regulation (Greene et al. 1996, 2001). Although the diagnosis of Along with EF deficits, socioemotional impairments are fre-
ADHD is established on the basis of behavior, cognitive deficits quently reported in ADHD (Nijmeijer et al. 2008; Uekermann
can be detected especially in the domain of executive function et al. 2010). Charman et al. (2001) found that children with ADHD
(EF) (Willcutt et al. 2005). had lower social competencies, as assessed by parental question-
Some attention impairments or executive deficits in children naires, and made more errors in an executive inhibition task, yet
with ADHD can be associated with theory of mind (ToM) dys- performed at the same level as normatively developing children in
function (Mary et al. 2016). Impairments in executive functioning, an executive planning task and in an advanced ToM paradigm.
associated with impaired attention, impulsivity, and distractibility, Comorbidities, such as oppositional defiant disorder (ODD),
may affect the ability of a child to perceive the perspective of pervasive developmental disorder (PDD), or conduct disorder
others. Thus, it is likely that stimulants have a beneficial effect on (CD) can be considered additional risk factors for socioemotional
social responsiveness in children with ADHD. In addition, the dysfunction in ADHD, including deficiency in empathy (Nijmeijer
lateral prefrontal cortex is an important node in the social brain, et al. 2008).

1
Child and Adolescent Outpatient Clinic, Geha Mental Health Center, Petah Tikva, Israel.
2
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
3
Research Unit, Geha Mental Health Center, Petah Tikva, Israel.
4
Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel.

429
430 GOLUBCHIK AND WEIZMAN

Methylphenidate (MPH) possesses agonistic dopamine and Measures


norepinephrine activity and is the treatment of choice in ADHD, Rating scales. ADHD-RS for ADHD. ADHD-RS is a
affecting impulsivity and aggression positively in ADHD pediatric clinician-rated, 18-item scale with one item for each of the 18
populations. While there are numerous reports on the influence of DSM-IV symptom criteria for ADHD, each rated on a severity
MPH treatment on emotional regulation (Williams et al. 2008), scale of 0 (not present) to 3 (severe). The questionnaire’s overall
little is known about its effect on empathy. Maoz et al. (2014) found minimal score = 0 and maximal score = 54 (DuPaul et al. 1998a,
that administration of MPH was associated with improvement in 1998b). A larger score indicates higher severity of ADHD. The
cognitive and ToM performance. scale was administered by a clinician as a semistructured interview
There is a scarcity of studies on this difficult to manage phe- with the children and their parents at the first visit and again at the
nomenon in pediatric ADHD and on the impact of MPH treatment last one 3 months later, to monitor changes in ADHD symptom
on empathy levels. In the present study baseline scores in the severity.
Empathizing Quotient—Children’s Version (EQ-C) questionnaire
(Auyeung et al. 2009) of children diagnosed with ADHD only K-SADS-PL for ODD. Psychiatric diagnosis of ODD was
(ADHD) were compared with those of children diagnosed with established through semistructured clinical interviews of the chil-
ADHD comorbid with ODD (ADHD/ODD). In addition, changes dren and their parents that followed the guidelines of the K-SADS-
in Empathizing Quotient (EQ) levels were monitored for the 3 PL (Kaufman et al. 2000). None of the participants met the DSM-
months following MPH treatment. The authors hypothesized that IV-TR criteria for CD.
the level of EQ would be higher in ADHD than in ADHD/ODD and
that MPH treatment would improve EQ in ADHD patients, but not EQ-C scale for empathy. EQ-C scale (27 Empathy items)—
parent version, was derived from the combined EQ-C/Children’s
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in ADHD/ODD ones.
Systemizing Quotient (SQ-C) (Auyeung et al. 2009). This Likert-
format questionnaire contains a list of statements about real-life
Methods
situations, experiences, and interests that require empathizing
Subjects abilities. Measures showed good test–retest reliability and high
internal consistency. Responses that score 1 or 2 points are re-
Fifty-two children aged 8–18 years of whom 26 were diag-
corded, while other responses score 0. For total score, sum of all
nosed with ADHD and the other 26 with ADHD/ODD were
items was calculated. The higher the score on this scale the more
recruited at a Maccabi Children’s Psychiatric Clinic in Rishon
empathic the person (Chapman et al. 2006). The EQ-C was com-
Lezion, Israel during the period from January 2012 to December
pleted by the parents.
2013. All participants were recruited from the same child psy-
chiatry clinic.
All the children met criteria for ADHD, according to the Di- MPH treatment procedure
agnostic and Statistical Manual of Mental Disorders, 4th ed., Text All participants received daily doses of 0.5–1.0 mg/kg of MPH
Revision (DSM-IV-TR) (American Psychiatric Association 2000) treatment. The daily doses did not exceed 60 mg/day. The trial was
as was established by semistructured clinical interviews with the conducted for 12 weeks. At baseline (baseline, time point 0) and at
children and their parent(s) using the Kiddie-Schedule for Affec- endpoint (time point 12 weeks), the patients were assessed by both
tive Disorders and Schizophrenia—Present and Lifetime Version the ADHD-RS and the EQ-C scales. They did not receive any other
(K-SADS-PL), and the ADHD Rating Scale (ADHD-RS) (DuPaul treatment during the course of this trial.
et al. 1998a, 1998b) that was completed by the parents. The diag-
nosis of the 26 children who also met DSM-IV-TR criteria for ODD
Safety and tolerability
was established by the K-SADS-PL combined with the parent and
teacher reports. All the children attended regular school during the The safety and tolerability of the treatment were evaluated at
study period and all came from similar socioeconomic background. baseline and at end point and also through spontaneous self-reports
All the children were psychostimulant-medication naive and were of adverse effects throughout the study period. Participants were
referred for assessment at the clinic by a pediatrician, a school able to report side effects by telephone at any time during the study.
consultant, or by the parents.
The study was approved by the Maccabi Health Services Review Statistical analysis
Board for Human Clinical Studies. All participants and their par-
ents gave written informed consent for participation in the study. Two-tailed, paired Student’s t-test and Spearman’s correlation
test were used as appropriate. All results are expressed as
mean – standard deviation.
Exclusion criteria. History of organic brain syndrome, sub-
stance use, mental retardation, CDs, bipolar disorder, schizophrenia,
Results
delusional disorder or suicidal ideation, and autistic spectrum disorder.
ADHD-RS scores in the ADHD/ODD
Procedure and ADHD groups
Diagnosis. The diagnoses of DSM-IV-TR ADHD and ODD No significant pretreatment differences in ADHD severity, as
were established through interviews conducted by board-certified assessed by the ADHD-RS, were found between the ADHD/ODD
senior child and adolescent psychiatrists, who followed the group (N = 26) and the ADHD group (N = 26), 17.8 – 11.5 versus
guidelines of K-SADS-PL (Kaufman et al. 2000). 21.8 – 11; unpaired t = 1.30, df = 50, p = 0.22.
The severity of ADHD was assessed by the clinician using the A significant reduction in the ADHD-RS scores was detected
ADHD-RS (DuPaul et al. 1998a, 1998b). The severity of ODD was following MPH treatment in both the ADHD/ODD group (before
assessed using the K-SADS-PL (Kaufman et al. 2000). and after: 17.8 – 11.5 vs. 14.1. – 8.6; paired t = 3.9, df = 25,
MPH EFFECT ON EMPATHY IN ADHD KIDS+/-ODD 431

p < 0.001) and the ADHD group (before and after: 21.8 – 11 vs. contribute to the social impairments that are commonly associated
16.6 – 8.5; paired t = 5.64, df = 25, p < 0.0001). with ADHD. In addition, including a relevant comorbid condition
(i.e., ODD) and comparing children with and without this co-
Baseline EQ-C scores in ADHD/ODD morbidity contribute to clarification of the relationship among
versus ADHD group ADHD, treatment with stimulants, and empathy.
Significantly lower baseline EQ-C scores were observed in
the ADHD/ODD (N = 26) group compared with the ADHD group Limitations
(N = 26) (32.3 – 8.4 vs. 38.3 – 6.2, respectively; unpaired t-test, The main limitations of the current study are the open label
t = 2.9, df = 50, p = 0.005). design, the small sample size, the relatively short treatment dura-
tion (12 weeks), and the lack of long-term follow-up.
The impact of MPH treatment on EQ-C scores The ODD patients were diagnosed according to DSM-IV-TR
in the ADHD/ODD and ADHD groups criteria, but no additional assessment tools were used to evaluate
Attention-deficit/hyperactivity disorder. A modest, but sta- subdimensional differences in this population, such as neurocog-
tistically significant increase in the EQ-C scores was obtained in the nitive battery or specific questionnaires. It should be noted that the
ADHD group (N = 26) following MPH treatment (before vs. after: semistructured interview used in the current study, namely the
38.3 – 6.2 vs. 40.5 – 5.9 paired t-test = 3.5, df = 25, p = 0.002). K-SADS, provides a categorical diagnosis of ODD and is not a
good indicator of its severity. In addition, both main outcome
measures were parent-based (ADHD-RS and EQ-C) and may be
Attention-deficit/hyperactivity disorder/ODD. A similar biased by expectancy effects. Furthermore, the primary outcome
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significant increase in the EQ scores was detected in the ADHD/ of interest, namely empathy, was measured by the Empathy
ODD group (N = 26) following MPH treatment (before and after: Quotient-Parent report. Thus, the results may reflect the parents’
32.3 – 8.2 vs. 36.2 – 9.8; paired t = 3.25, df = 25, p = 0.003). The perception of their child’s empathy. In addition, EQ-C has been
improvements in EQ levels (D) were similar in both groups (ADHD validated in 4- to 11-year olds while the present study included
alone vs. ADHD/ODD 2.0 – 3.0 vs. 3.9 – 5.0; t = 1.66, df = 50, adolescents. There is, however, a marked similarity between the
p = 0.10), thus it is unlikely that the existence of ODD moderated EQ-C and the adolescent EQ scale that was developed later
the response of EQ-C to MPH treatment. (Auyeung et al. 2012). Another limitation consists of the rela-
tively low ADHD-RS scores at baseline and modest changes in
Correlations ADHD symptoms (4–5 points on ADHD-RS) found in both
Significant correlation was found between the changes in groups. Those could be accounted for by time, as well as expec-
ADHD-RS and EQ scores after MPH treatment in the ADHD group tancy effects. These methodological weaknesses limit the ability
(Spearman’s r = 0.47, p = 0.015), but not in the ADHD/ODD group to generalize the findings of the present study.
(Spearman’s r = 0.14, p = 0.48). It is suggested that a future study with a similar design, in-
vestigating the impact of MPH treatment on empathy, should
Discussion include children diagnosed with ADHD and CD with callous-
emotional traits.
The aim of the present study was to compare the baseline levels
of EQ, as well as the changes in EQ levels following 3 months MPH Conclusions
treatment, in children diagnosed with ADHD to those with ADHD/
ODD. The authors hypothesized that at baseline, the level of em- MPH treatment may bring a modest improvement in empathy of
pathy as assessed by EQ-C would be larger in ADHD children than patients diagnosed with ADHD, whether comorbid or not with
in ADHD/ODD children. Furthermore, it was assumed that EQ-C ODD. It is possible that empathy deficiency in ODD patients relates
would be enhanced in the ADHD population by the MPH treatment, to multiple factors, including anxiety and callous-emotional traits.
while no such finding was expected in the ADHD/ODD group. Unfortunately we did not measure real-life empathy functioning,
The findings indeed showed the hypothesis to be true, as baseline thus it is unclear whether the modest improvement in EQ-C scores
EQ-C was found to be significantly lower in ADHD/ODD children is clinically significant in youths diagnosed with ADHD with or
in comparison to ADHD children. without ODD.
In addition, the MPH treatment led to significant improvement in
EQ in both the ADHD ( p < 0.002) and ADHD/ODD ( p < 0.003) Clinical Significance
groups. Thus it seems that ODD without comorbid CD does not
In addition to the expected beneficial effect of MPH treatment on
interfere with the beneficial effect of MPH on EQ.
the core ADHD symptomatology in children and adolescents di-
Improvement of empathy level in ADHD children without ODD
agnosed with ADHD, but not with ODD, the treatment may also
was shown recently by Maoz et al. (2014). In that study, adminis-
improve the level of empathy in this population.
tration of MPH to children diagnosed with ADHD, but not ODD,
was associated with improvement in cognitive and affective ToM,
Disclosures
as well as in empathy functioning. Thus it appears that MPH has a
beneficial effect on empathy irrespective of the absence or presence No competing financial interests exist.
of ODD.
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