International Journal of Psychiatry in Clinical Practice
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The effect of methylphenidate treatment on suspiciousness in children with ADHD alone or comorbid with ODD Pavel Golubchik & Abraham Weizman To cite this article: Pavel Golubchik & Abraham Weizman (2017): The effect of methylphenidate treatment on suspiciousness in children with ADHD alone or comorbid with ODD, International Journal of Psychiatry in Clinical Practice, DOI: 10.1080/13651501.2017.1383436 To link to this article: http://dx.doi.org/10.1080/13651501.2017.1383436
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Date: 01 October 2017, At: 09:13
INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE, 2017 https://doi.org/10.1080/13651501.2017.1383436
ORIGINAL ARTICLE
The effect of methylphenidate treatment on suspiciousness in children with ADHD alone or comorbid with ODD Pavel Golubchika,c and Abraham Weizmanb,c,d
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a Child and Adolescent Outpatient Clinic, Geha Mental Health Center, Petah Tikva, Israel; bResearch Unit, Geha Mental Health Center, Petah Tikva, Israel; cSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; dFelsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel
ABSTRACT
ARTICLE HISTORY
Objective: To assess the level of the suspiciousness in children with attention deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) in comparison to ADHD alone and the response of suspiciousness symptoms to methylphenidate (MPH) treatment. Methods: In this open-label comparative study, children with DSM-IV-TR ADHD, aged 8–18 years, with (N ¼ 30) or without (N ¼ 30) ODD received MPH treatment for 12 weeks. The severity of ODD symptoms was assessed by the Kiddie–Schedule for Affective Disorders and Schizophrenia. The severity of ADHD symptoms was assessed by the ADHD-Rating-Scale-IV and suspiciousness was assessed at baseline and at endpoint by a scale designed especially for assessment of suspiciousness and named Suspiciousness Rating Scale (SRS). Results: Significant reductions in SRS scores were detected in both groups following MPH treatment (before and after: p ¼ .0012 and p ¼ .0273, respectively). Only in the ADHD/ODD group a significant correlation was found between the rate of improvement in ADHD, as assessed by the ADHD–RS, and the reduction in suspiciousness, as assessed by the SRS (Spearman r ¼ 0.48, p ¼ .0066). Conclusions: In addition to the beneficial effect of MPH treatment on ADHD and ODD symptoms it also diminishes suspiciousness. However, due to the small sample size further studies are needed to confirm the present results.
Received 27 June 2016 Revised 14 September 2017 Accepted 18 September 2017
Objectives The prevalence of attention deficit/hyperactivity disorder (ADHD) ranges from 1% to 8% (Stuhec, Svab, & Locatelli, 2015b). ADHD has been associated with aggressive and oppositional behaviour, with co-morbid oppositional defiant disorder (ODD) and with conduct disorder (CD) (Harvey, Breaux, & Lugo-Candelas, 2016; Reale et al., 2017). In addition to the high levels of aggression, there is impairment in the proper understanding of social situations, leading to often misinterpreting social interactions and perceiving them as threatening thus leading to suspiciousness (Nijmeijer et al., 2008). Little is known about the underlying mechanisms of this misperception which seems to resemble paranoid thinking. Bailey, Whittle, Farnworth, and Smedley (2007) explored the relationship between antisocial behaviour in adolescence and the development of paranoid thinking. They reported substantially higher rates of aggressive behaviour in children and adolescents who met the criteria for ADHD, ODD and conduct disorder. Children with hyperactivity, impulsivity, attention deficits and serious conduct problems may also be at risk for developing psychopathy and distorted or biased thought processes. Over time these children display significant cognitive attributional bias in addition to their aggressive behaviour. Furthermore, they are more likely to perceive neutral acts by others as hostile. Such hostile attributions may stem from Theory of Mind (ToM) dysfunction (Choe, Lane, Grabell, & Olson, 2013) which is frequently associated with ADHD (Mary et al., 2016). Children with a less sophisticated interpretation of emotion, particularly those who have difficulty CONTACT Pavel Golubchik
[email protected]
ß 2017 Informa UK Limited, trading as Taylor & Francis Group
KEYWORDS
Attention deficit/ hyperactivity disorder (ADHD); oppositional defiant disorder (ODD); suspiciousness; methylphenidate (MPH); children and adolescents
differentiating others’ emotions from their own, are more prone to making hostile attributions. Additionally, children with ADHD have difficulties in social cognition and frequently react inappropriately in social interaction. They may also respond in an aggressive and suspicious manner due to misinterpreting other people’s behaviour as threatening (Yuill & Lyon, 2007). Such social-cognitive deficit in children may be explained by difficulties to perceive and interpret emotions such as anger, pleasure or sadness in others (Uekermann et al., 2010) and thus they are prone to over-attribute hostile intentions to peers (hostile attribution bias). Such bias was reported in children with aggressive behaviours, an observation that may be relevant to children with ODD (Vassilopoulos, Brouzos, & Andreou, 2015). Methylphenidate (MPH) stimulates dopaminergic and noradrenergic neurotransmission and suppresses impulsivity and aggression in children with ADHD. It is the treatment of choice in pediatric populations diagnosed with ADHD (Bolea-Alamanac et al., 2014). Numerous studies report on the influence of MPH treatment on emotion recognition (Williams et al., 2008), however, little is known about its effect on suspiciousness. The main objectives of the present study were to assess the level of suspiciousness in children suffering from ADHD with comorbid ODD and compare it to ADHD alone as well as to assess the response of suspiciousness symptoms to 12 weeks of MPH treatment. Our hypothesis was that the suspiciousness level would be higher in ADHD/ODD as compared to ADHD alone, and that MPH treatment would not worsen the baseline suspiciousness but
Child and Adolescent Outpatient Clinic, Geha Mental Health Center, PO Box 102, Petah Tiqva 49100, Israel
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rather bring some improvement in suspiciousness, mainly in those with comorbid ODD.
Methods
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Subjects Inclusion criteria consisted of meeting DSM-IV-TR ADHD criteria with and without DSM-IV-TR ODD, age 8–18 years and no current administration of pharmacological treatment. Sixty children, 30 diagnosed only with ADHD and the other 30 with ADHD and ODD, were recruited at a Maccabi children’s psychiatric clinic in Rishon Lezion, Israel. All 60 children met DSM-IV-TR ADHD criteria, established by a semi-structured clinical interview of the children and their parent(s) using the Kiddie-Schedule for Affective Disorders and Schizophrenia – Present and Lifetime Version (K-SADS-PL) as well as by both the parents’ and teachers’ – reports using the Attention Deficit Hyperactivity Disorder – Rating Scale (ADHD-RSIV) (DuPaul, Barkley, & McMurray, 1994). Thirty of the children also met the DSM-IV-TR criteria for ODD, as established by the two tools mentioned above (DuPaul, Power, Anasopoulos, & Reid, 1998). The children were evaluated in the presence of their parents. All children attended regular school at the time of the study and all were from similar socio-economic background. All children were psychostimulant medication naïve and were referred for assessment by a paediatrician, school consultant or by the parents. The study was approved by the Maccabi Health Services Review Board for Human Clinical Studies. All participants and their parents provided consent in writing for their participation in the study after the study was explained to them. Exclusion criteria: History of organic brain syndrome, substance use, mental retardation, bipolar disorder, schizophrenia, a physical disease, delusional disorder or suicidal ideation. Diagnosis Treatment The diagnoses of DSM-IV-TR ADHD and ODD were established based on an interview with the children and their parents that was conducted by a board-certified senior child and adolescent psychiatrists and followed the guidelines of K-SADS-PL (Kaufman, Birmaher, Brent, Ryan, & Rao, 2000). The severity of ADHD was assessed by the ADHD Rating Scale (ADHD-RS-IV) (DuPaul et al., 1998). The severity of ODD was assessed by the K-SADS-PL (Kaufman et al., 2000) and was defined by the authors as ODD/K-SADS-PL score. Treatment All eligible patients received daily doses of 0.5–1.0 mg/kg of MPH – doses in the range recommended by the British Association for Psychopharmacology (Bolea-Alamanac et al., 2014). The patients were assessed by ADHD-RS-IV at baseline (day-1) and at endpoint (at the end of week 12). The daily dose did not exceed 60 mg/ day. Daily MPH doses were adjusted for all participants according to the response at the end of week 2 and at the end of week 4. The MPH formulations were MPH-IR, administered twice a day (N ¼ 15) or MPH-LA (N ¼ 26) or OROS-MPH (Concerta) (N ¼ 19) which were administered once a day. The distribution of the formulations did not differ significantly between the two groups. Throughout the study period the patients were kept off all other medications.
Measures Rating scales (1) ADHD-RS-IV (DuPaul et al., 1994): A clinician-rated, 18-item scale with one item for each of the 18 DSM-IV symptom criteria for ADHD on a severity scale of 0 (not present) to 3 (severe); overall minimal score ¼ 0 and a maximal score ¼ 54. It was used as a clinician-administered, semi-structured parent–child interview at first and last (3 month) visits to monitor ADHD symptom severity. (2) Semi-structured clinical interview of the child and the child’s parent(s) according to the guidelines of K-SADS-PL (Kaufman et al., 2000). (3) Suspiciousness Rating Scale (SRS) was especially designed for this study. This tool measures misinterpretation of social situations as being threatening. The range of this scale is 1 (not present) to 3 (severe); overall minimal score ¼ 4 and a maximal score ¼ 12. See Appendix 1. The first three questions are derived from items 34, 38 and 89 from The Child Behaviour Checklist (CBCL) (Achenbach, 1991) and are as follows: Item 1 is based on CBCL-38 Feels that others tease him/her a lot, Item 2 is based on CBCL-34 Feels that others are out to get him/her and Item 3 is based on CBCL-89 Suspicious. The last question was taken from the Conners’ Parent Rating Scale (Conners, Sitarenios, Parker, & Epstein, 1998), item 61and reads: Blames others for his/her mistakes or misbehaviour (equivalent to over-attributing hostile intentions to peers). All the questionnaires and interviews were completed during the first visit, 1 day prior to initiation of MPH treatment and again after 3 months of treatment. The trial was conducted for 12 weeks. Safety The safety of the treatment was evaluated at baseline and at endpoint. Spontaneous reports by participants on adverse effects were recorded. The spontaneous reports could be called in by telephone at any time during the study. A clinical pharmacist dispensed the medications to the patients, but the monitoring for adverse events was conducted by the psychiatric researcher (PG). Statistical analysis Two-tailed, paired and unpaired Student’s t-tests and Spearman’s correlation test were used as appropriate. Cronbach’s a test was used to assess the internal consistency for the SRS. All results are expressed as Mean ± SD and p < .05 was considered statistically significant.
Results Age and gender Sixty children and adolescents (35 boys and 25 girls), aged 12.5 ± 2.5 years were included in the study. The ADHD group aged 12.9 ± 2.5 and the ADHD/ODD group aged 11.6 ± 1.2 years. ADHD-RS-IV scores in the ADHD subjects with and without/ODD Severity of ADHD prior to treatment, as assed by the ADHD-RS-IV was significantly greater in the ADHD/ODD group (N ¼ 30) as compared to the ADHD alone group (N ¼ 30): 26.6 ± 9.9 versus 16.7 ± 10.8; paired t ¼ 3.2, df ¼ 29, p < .0034. A significant reduction in the ADHD-RS-IV scores was detected following MPH treatment in both the ADHD/ODD group (N ¼ 30; before and after: 26.6 ± 9.9 versus 19.9 ± 7.7; paired t ¼ 9.4, df ¼ 29, p < .0001) and in the ADHD group (N ¼ 30; before and after: 16.7 ± 10.8 versus 13.1 ± 8.3; paired t ¼ 3.2, df ¼ 29, p < .0034).
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Table 1. Correlations between the baseline levels and changes following methylphenidate treatment in the ADHD-RS-IV, ODD/K-SADS-PL and the SRS scores. Correlations between changes in scores following MPH treatment
Correlations in baseline scores D in Scale-Pairs ODD/K-SADS-PL with SRS (ADHD/ODD group) ODD/K-SADS-PL with SRS (ADHD group) ADHD-RS-IV with SRS (ADHD/ODD group) ADHD–RS-IV with SRS (ADHD group) ADHD-RS-IV versus ODD/KSADS-PL (ODD/ADHD Group) ADHD-RS-IV versus ODD/KSADS-PL (ADHD Group)
Spearman r
95% CI
p
Spearman r
95% CI
p
0.09 0.35 0.07 0.13 0.10 0.27
0.4 to 0.28 0.6 to 0.005 0.42–0.29 0.24–0.47 0.26 to 0.45 0.09 to 0.58
.63 .054 .69 .49 .58 .14
0.22 NA 0.48 0.21 0.19 NA
0.15 to 0.54
.24
0.14–0.72 0.54 to 0.17 0.17 to 0.52
.0066 .25 .30
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ADHD-RS-IV, ADHD Rating Scale; ADHD, attention deficit/hyperactivity disorder; ODD, oppositional defiant disorder; ODD/K-SADS-PL, ODD criteria in semi-structured clinical interviews of the child; MPH: methylphenidate; SRS: suspiciousness rating scale; NA: non-applicable (baseline ODD/K-SADS-PL were very low). Remains significant following Bonferroni correction.
ODD severity
Psychometric properties of SRS
According to the ODD/K-SADS-PL, the severity of ODD at the beginning of the study was 6.6 ± 1.4 in the ADHD/ODD group (N ¼ 30) and 3.1 ± 0.4 in the ADHD group (N ¼ 30), with unpairedt ¼13.17, df ¼ 58, p ¼ .0001. After the 12-week MPH treatment, a very modest but significant reduction improvement was found in ODD severity in the ADHD/ODD group (N ¼ 30), namely, ODD/K-SADS-PL scores for ODD dropped from 6.6 ± 1.4 at the start to 5.1 ± 1.1, (paired t ¼ 6.4, df ¼ 29, p < .0001).
The internal consistency of the SRS was found to be good, with Cronbach’s a ¼ 0.76. Excluding any item would not improve the internal consistency of this scale (corrected item total correlation for all items was 0.46). Item 1 on the SRS is based on subjective impression of being teased by others. Thus, in order to ascertain the relevance to suspiciousness of item 1 in the SRS (derived from item 89 in the CBCL), we analysed the inter-correlation coefficients between this item and the other three items on the SRS. The inter-correlation coefficients were found to be fairly good, r 0.32.
Baseline SRS scores in ADHD/ODD versus ADHD group
Safety
Significantly larger baseline SRS scores were obtained in the ADHD/ODD (N ¼ 30) group as compared to the ADHD (N ¼ 30) group (8.6 ± 2.0 versus 6.5 ± 2.1, respectively; unpaired t-test, t ¼ 3.97, df ¼ 58, p ¼ .0002).
Despite the pro-paranoid effect of stimulants (Bramness & Rognli, 2016; Kollins, 2008) both ADHD and ADHD/ODD groups displayed no signs of worsening in the level of suspiciousness and no de novo emergence of delusional/psychotic symptoms. No clinically significant complains regarding intolerable insomnia or appetite suppression were reported by the participants or their parents. Neither were there any cases of attrition from the study.
The impact of MPH treatment on SRS scores in the ADHD/ODD and ADHD groups A slight but significant reduction in the SRS scores was detected in the ADHD/ODD group (N ¼ 30) following MPH treatment (before and after: 8.6 ± 2.0 versus 7.9 ± 2.0; paired t ¼ 3.9, df ¼ 29, p < .0012). A very slight, but statistically significant, reduction in the SRS scores was also obtained in the ADHD group (N ¼ 30) following MPH treatment (before versus after: 6.5 ± 2.0 versus 6.2 ± 2.0, paired t-test ¼ 2.5, df ¼ 29, p < 0.018). Correlations between scales Baseline scores The correlations between the baseline scores of the various scales, within the ADHD/ODD and ADHD groups, are described in Table 1. As shown, no significant correlations were found between: baseline ODD/K-SADS-PL and SRS scores, baseline ODD/ K-SADS-PL and ADHD-RS-IV scores and SRS and ADHD-RS-IV scores in both the ADHD/ODD and ADHD groups. Changes in scores following MPH treatment The correlations between the changes in the ADHD-RS-IV, ODD/KSADS-PL and the SRS scores are described in Table 1. A significant correlation was found between the changes in ADHD-RS-IV and SRS scores after MPH treatment in the ADHD/ODD group but not in the ADHD group. No significant correlations were found between the changes in SRS and ODD/K-SADS-PL scores or between the changes in ADHD-RS-IV and ODD/K-SADS-PL scores in the ADHD/ODD group.
Discussion Suspiciousness The aim of the present study was to evaluate the impact of 12weeks of MPH treatment on suspiciousness in ADHD and ADHD/ ODD patients. Significantly (p ¼ .0002) larger baseline SRS scores were observed in the ADHD/ODD group (N ¼ 30) than in the ADHD (N ¼ 30) group. This finding supports our hypothesis that the severity of suspiciousness (i.e., often feeling teased, blaming others, feeling others are out to get you and feeling suspicious of others) is larger among ADHD patients with ODD than in those without ODD although even in those without ODD there is a certain level of suspiciousness. Significant reductions in suspiciousness (SRS scores) were observed after MPH treatment in both groups, probably due to the alleviation of ADHD symptoms in both groups. The neurobiological mechanism(s) involved in the anti-suspiciousness effect in ADHD with or without ODD, is(are) as yet unclear. ODD Serra-Pinheiro, Mattos, Souza, Pastura, and Gomes (2004) evaluated the effect of MPH on ODD comorbid with ADHD and reported similar findings to those of the current study, namely, improvement in ODD severity. In that study, MPH was found to be an effective treatment for ODD, as well as for the ADHD and nine of the 10 participants no longer met the diagnostic criteria for ODD after MPH treatment for their ADHD (Serra-Pinheiro et al., 2004). Sinzig, Dopfner, Lehmkuhl, Uebel, and Schmeck (2007) showed in a double-blind, randomized, 5-week clinical trial that long-
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acting MPH was effective for oppositional-defiant and aggressive behaviour, especially at school. In another study, MPH treatment was found significantly effective for oppositional symptoms in adult ADHD population, especially in patients with emotional dysregulation (Marchant, Reimherr, Robison, Olsen, & Kondo, 2011). Significant reductions in severity of SRS scores were detected in both groups following MPH treatment (before and after twotailed Student’s paired t tests: p ¼ .0012 and p ¼ .03, respectively). However, only in the ADHD/ODD group, a significant correlation was found following MPH treatment, between the improvement in ADHD, as assessed by the ADHD–RS, and the reduction in suspiciousness, as assessed by the SRS (Spearman r ¼ 0.48, p ¼ .0066). The lack of a positive correlation in the ADHD/ODD group at baseline between level of suspiciousness (SRS score) and either ODD score (ODD/K-SADS-PL/ODD score; Spearman r ¼ 0.09, p ¼ .63) or ADHD-RS-IV score (Spearman r ¼ 0.35, p ¼ .054) as well as the significant reduction of suspiciousness in both groups following MPH treatment indicate that the relationship between ODD and suspiciousness in children with ADHD is complex and merits further investigation in larger groups. Nevertheless, the results support this study’s hypothesis, that improvement in ADHD symptoms is associated with marked attenuation in suspiciousness levels in ADHD/ODD patients. The possible explanation for such simultaneous improvement may be related to a reciprocal relationship between ADHD and ODD in this sub-population (ADHD/ODD group). Recurrent ADHD/ODDrelated social disappointment, social rejection and misperception/ misrecognition of social cues in these patients may have a part in the evolution of the suspiciousness. Thus, when the severity of ADHD diminishes with MPH treatment there is a parallel attenuation in suspiciousness. MPH-related improvements in academic capacity, self-control, self-competence and self-confidence may lead to more suitable and acceptable social interactions and less social conflicts (Kats-Gold, Besser, & Priel, 2007). Similar relations were detected between poorer executive function (EF) and symptoms of ADHD and/or ODD (Skogan et al., 2014). Thus, it is possible that poor cognitive functioning in ADHD/ODD patients contributes to the emergence of suspiciousness. It is of note that Beyer von Morgenstern, Becker, and Sinzig (2014) have shown improvement of facial affect recognition in children and adolescents with ADHD when treated with MPH. Improvement in affect recognition, reward sensitivity and executive functioning (Poulton & Nanan, 2014) following MPH treatment may also play a role in reduction in suspiciousness in the ADHD/ ODD participants of the current study. Safety Both ADHD and ADHD/ODD groups displayed no signs of worsening in the level of suspiciousness and no de novo emergence of delusional/psychotic symptoms. Neither were there any cases of attrition from the study. However, the validity of the data, concerning the safety of MPH treatment in this unique population, is limited due to the relatively short duration of the study and the small sample size. Nevertheless, the findings of this study suggest that MPH treatment may be an effective intervention in ADHD/ODD children with significant levels of suspiciousness. Limitations The main limitations of this study are the open label design, the small sample size, the mild severity of the ADHD of the studied population, the relatively short treatment duration (12 weeks) and
the lack of long-term follow-up. In addition despite its good psychometric properties and reliability, there are possible limitations of the SRS. The four items of the SRS may differ in the level of the participant’s suspiciousness, ranging from feeling that others are teasing him/her (item 1), through acknowledging cognitive biases of blaming others for his/her mistakes or misbehaviour (item 4), to a general impression regarding his/her own degree of suspiciousness (item 3) and of feelings that others are out to get him/ her (item 2). The scale needs further validation in populations with more severe ADHD and ODD as well as in other pediatric psychopathologies associated with suspiciousness. Furthermore, there are some major confounding factors which may affect the results, like: the quality (or ability) of the participants’ social cognition, their level of anxiety, traumatic experiences and level of self-esteem. Moreover, since there is no group with ODD alone (without ADHD), the association between suspiciousness and ADHD þ ODD needs further validation. It should be noted that adverse events were reported by the patients or their parents with no corresponding rating scales. Thus, the data on adverse events reflect only safety and not tolerability. Additionally, there is no comparison to other anti-ADHD treatments like amphetamine, clonidine, guanfacine or atomoxetine. Still, it appears that MPH, and maybe other stimulants and nonstimulants may ameliorate suspiciousness in ADHD with and without ODD.
Conclusion This study demonstrates that MPH treatment seems to be relatively safe in ADHD/ODD patients and to diminish suspiciousness levels in this population. Furthermore, it shows that suspiciousness is higher in AHDH/ODD compared to ADHD alone and decreases following MPH treatment in both groups, indicating that suspiciousness may be considered a treatable state (versus trait). Namely, it is possible that alleviation of ADHD achieved by MPH treatment is accompanied by a corresponding relief in suspiciousness, especially in comorbid ODD. Moreover, it appears that in addition to the beneficial effect of MPH treatment in ADHD, and to some extent in ODD symptoms, it also diminishes suspiciousness in children with ADHD. These data are of clinical importance in the field of ADHD, especially in the current situation where only about half of those suffering of ADHD receive an adequate treatment despite the disabling nature of the disorder (Stuhec, 2016; Stuhec & Locatelli, 2017). However, further large-scale, double-blind, placebo-controlled studies, including 2 comparison to non-stimulants, like atomoxetine, bupropion and a adrenergic agonists (Stuhec, Munda, Svab, & Locatelli, 2015a), are required to substantiate and generalize our observations.
Acknowledgements The authors thank Dr Tomer Levi for calculating the psychometric properties of the SRS.
Disclosure statement None to declare.
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Poulton, A., & Nanan, R. (2014). The attention deficit hyperactivity disorder phenotype as a summation of deficits in executive functioning and reward sensitivity: Does this explain its relationship with oppositional defiant disorder? Australasian Psychiatry, 22, 174–178. doi: 10.1177/1039856213517949 Reale, L., Bartoli, B., Cartabia, M., Zanetti, M., Costantino, M. A., Canevini, M. P., … Lombardy ADHD Group. (2017). Comorbidity prevalence and treatment outcome in children and adolescents with ADHD. European Child & Adolescent Psychiatry. doi: 10.1007/s00787-017-1005-z. [Epub ahead of print] Serra-Pinheiro, M. A., Mattos, P., Souza, I., Pastura, G., & Gomes, F. (2004). The effect of methylphenidate on oppositional defiant disorder comorbid with attention deficit/hyperactivity disorder. Arquivos de Neuro-Psiquiatria, 62, 399–402. doi: 10.1590/S0004282X2004000300005 Sinzig, J., Dopfner, M., Lehmkuhl, G., German Methylphenidate Study Group, Uebel, H., Schmeck, K., … , Fischer R. (2007). Longacting methylphenidate has an effect on aggressive behavior in children with attention-deficit/hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology, 17, 421–432. doi: 10.1089/cap.2007.0011 Skogan, A. H., Zeiner, P., Egeland, J., Rohrer-Baumgartner, N., Urnes, A. G., Reichborn-Kjennerud, T., & Aase, H. (2014). Inhibition and working memory in young preschool children with symptoms of ADHD and/or oppositional-defiant disorder. Child Neuropsychology, 20, 607–624. doi: 10.1080/ 09297049.2013.838213 Stuhec, M. (2016). Pharmacotherapy of ADHD in Slovenia: Realities and perspectives. European Child and Adolescent Psychiatry, 25, 455–457. doi: 10.1007/s00787-015-0811-4 Stuhec, M., & Locatelli, I. (2017). Age-related pharmacotherapy of attention deficit hyperactivity disorder in Slovenia in children and adolescents: A population-based study. European Psychiatry, 42, 129–133. doi: 10.1016/j.eurpsy.2017.01.002 Stuhec, M., Munda, B., Svab, V., & Locatelli, I. 2015a. Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine, bupropion and methylphenidate in treatment of attention deficit hyperactivity disorder in children and adolescents: A metaanalysis with focus on bupropion. Journal of Affective Disorders, 178, 149–159. Stuhec, M., Svab, V., & Locatelli, I. (2015b). Prevalence and incidence of attention-deficit/hyperactivity disorder in Slovenian children and adolescents: A database study from a national perspective. Croatian Medical Journal, 56, 159–165. Uekermann, J., Kraemer, M., Abdel-Hamid, M., Schimmelmann, B. G., Hebebrand, J., Daum, I., … Kis, B. (2010). Social cognition in attention-deficit hyperactivity disorder (ADHD). Neuroscience & Biobehavioural Review, 34, 734–743. doi: 10.1016/ j.neubiorev.2009.10.009 Vassilopoulos, S. P., Brouzos, A., & Andreou, E. (2015). A multi-session attribution modification program for children with aggressive behaviour: Changes in attributions, emotional reaction estimates, and self-reported aggression. Behavioural and Cognitive Psychotherapy, 43, 538–548. doi: 10.1017/S1352465814000149 Williams, L. M., Hermens, D. F., Palmer, D., Kohn, M., Clarke, S., Keage, H., … , Gordon E. (2008). Misinterpreting emotional expressions in attention-deficit/hyperactivity disorder: Evidence for a neural marker and stimulant effects. Biological Psychiatry, 63, 917–926. doi: 10.1016/j.biopsych.2007.11.022 Yuill, N., & Lyon, J. (2007). Selective difficulty in recognising facial expressions of emotion in boys with ADHD. General performance impairments or specific problems in social cognition? European Child & Adolescent Psychiatry, 16, 398–404. doi: 10.1007/s00787-007-0612-5
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Appendix 1 Four-item suspiciousness rating scale (SRS). Scores SRS items 1. 2. 3. 4.
Feels that others tease him/her a lot Feels others are out to get him/her Suspicious Blames others for his/her mistakes or misbehaviour
Absent
Occurs sometimes
Occurs frequently
1 1 1 1
2 2 2 2
3 3 3 3
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CBCL-38 Gets teased a lot, CBCL-34 Feels others are out to get him/her and CBCL-89 Suspicious. The last question was taken from the Conners’ Parent Rating Scale (Conners et al., 1998), item 61 and reads: Blames others for his/her mistakes or misbehaviour. Suspiciousness is an equivalent of hostile attribution bias.
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The effect of methylphenidate treatment on suspiciousness in children with ADHD alone or comorbid with ODD Pavel Golubchik & Abraham Weizman To cite this article: Pavel Golubchik & Abraham Weizman (2017): The effect of methylphenidate treatment on suspiciousness in children with ADHD alone or comorbid with ODD, International Journal of Psychiatry in Clinical Practice, DOI: 10.1080/13651501.2017.1383436 To link to this article: http://dx.doi.org/10.1080/13651501.2017.1383436
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Date: 01 October 2017, At: 09:13
INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE, 2017 https://doi.org/10.1080/13651501.2017.1383436
ORIGINAL ARTICLE
The effect of methylphenidate treatment on suspiciousness in children with ADHD alone or comorbid with ODD Pavel Golubchika,c and Abraham Weizmanb,c,d
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a Child and Adolescent Outpatient Clinic, Geha Mental Health Center, Petah Tikva, Israel; bResearch Unit, Geha Mental Health Center, Petah Tikva, Israel; cSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; dFelsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel
ABSTRACT
ARTICLE HISTORY
Objective: To assess the level of the suspiciousness in children with attention deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) in comparison to ADHD alone and the response of suspiciousness symptoms to methylphenidate (MPH) treatment. Methods: In this open-label comparative study, children with DSM-IV-TR ADHD, aged 8–18 years, with (N ¼ 30) or without (N ¼ 30) ODD received MPH treatment for 12 weeks. The severity of ODD symptoms was assessed by the Kiddie–Schedule for Affective Disorders and Schizophrenia. The severity of ADHD symptoms was assessed by the ADHD-Rating-Scale-IV and suspiciousness was assessed at baseline and at endpoint by a scale designed especially for assessment of suspiciousness and named Suspiciousness Rating Scale (SRS). Results: Significant reductions in SRS scores were detected in both groups following MPH treatment (before and after: p ¼ .0012 and p ¼ .0273, respectively). Only in the ADHD/ODD group a significant correlation was found between the rate of improvement in ADHD, as assessed by the ADHD–RS, and the reduction in suspiciousness, as assessed by the SRS (Spearman r ¼ 0.48, p ¼ .0066). Conclusions: In addition to the beneficial effect of MPH treatment on ADHD and ODD symptoms it also diminishes suspiciousness. However, due to the small sample size further studies are needed to confirm the present results.
Received 27 June 2016 Revised 14 September 2017 Accepted 18 September 2017
Objectives The prevalence of attention deficit/hyperactivity disorder (ADHD) ranges from 1% to 8% (Stuhec, Svab, & Locatelli, 2015b). ADHD has been associated with aggressive and oppositional behaviour, with co-morbid oppositional defiant disorder (ODD) and with conduct disorder (CD) (Harvey, Breaux, & Lugo-Candelas, 2016; Reale et al., 2017). In addition to the high levels of aggression, there is impairment in the proper understanding of social situations, leading to often misinterpreting social interactions and perceiving them as threatening thus leading to suspiciousness (Nijmeijer et al., 2008). Little is known about the underlying mechanisms of this misperception which seems to resemble paranoid thinking. Bailey, Whittle, Farnworth, and Smedley (2007) explored the relationship between antisocial behaviour in adolescence and the development of paranoid thinking. They reported substantially higher rates of aggressive behaviour in children and adolescents who met the criteria for ADHD, ODD and conduct disorder. Children with hyperactivity, impulsivity, attention deficits and serious conduct problems may also be at risk for developing psychopathy and distorted or biased thought processes. Over time these children display significant cognitive attributional bias in addition to their aggressive behaviour. Furthermore, they are more likely to perceive neutral acts by others as hostile. Such hostile attributions may stem from Theory of Mind (ToM) dysfunction (Choe, Lane, Grabell, & Olson, 2013) which is frequently associated with ADHD (Mary et al., 2016). Children with a less sophisticated interpretation of emotion, particularly those who have difficulty CONTACT Pavel Golubchik
[email protected]
ß 2017 Informa UK Limited, trading as Taylor & Francis Group
KEYWORDS
Attention deficit/ hyperactivity disorder (ADHD); oppositional defiant disorder (ODD); suspiciousness; methylphenidate (MPH); children and adolescents
differentiating others’ emotions from their own, are more prone to making hostile attributions. Additionally, children with ADHD have difficulties in social cognition and frequently react inappropriately in social interaction. They may also respond in an aggressive and suspicious manner due to misinterpreting other people’s behaviour as threatening (Yuill & Lyon, 2007). Such social-cognitive deficit in children may be explained by difficulties to perceive and interpret emotions such as anger, pleasure or sadness in others (Uekermann et al., 2010) and thus they are prone to over-attribute hostile intentions to peers (hostile attribution bias). Such bias was reported in children with aggressive behaviours, an observation that may be relevant to children with ODD (Vassilopoulos, Brouzos, & Andreou, 2015). Methylphenidate (MPH) stimulates dopaminergic and noradrenergic neurotransmission and suppresses impulsivity and aggression in children with ADHD. It is the treatment of choice in pediatric populations diagnosed with ADHD (Bolea-Alamanac et al., 2014). Numerous studies report on the influence of MPH treatment on emotion recognition (Williams et al., 2008), however, little is known about its effect on suspiciousness. The main objectives of the present study were to assess the level of suspiciousness in children suffering from ADHD with comorbid ODD and compare it to ADHD alone as well as to assess the response of suspiciousness symptoms to 12 weeks of MPH treatment. Our hypothesis was that the suspiciousness level would be higher in ADHD/ODD as compared to ADHD alone, and that MPH treatment would not worsen the baseline suspiciousness but
Child and Adolescent Outpatient Clinic, Geha Mental Health Center, PO Box 102, Petah Tiqva 49100, Israel
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P. GOLUBCHIK AND A. WEIZMAN
rather bring some improvement in suspiciousness, mainly in those with comorbid ODD.
Methods
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Subjects Inclusion criteria consisted of meeting DSM-IV-TR ADHD criteria with and without DSM-IV-TR ODD, age 8–18 years and no current administration of pharmacological treatment. Sixty children, 30 diagnosed only with ADHD and the other 30 with ADHD and ODD, were recruited at a Maccabi children’s psychiatric clinic in Rishon Lezion, Israel. All 60 children met DSM-IV-TR ADHD criteria, established by a semi-structured clinical interview of the children and their parent(s) using the Kiddie-Schedule for Affective Disorders and Schizophrenia – Present and Lifetime Version (K-SADS-PL) as well as by both the parents’ and teachers’ – reports using the Attention Deficit Hyperactivity Disorder – Rating Scale (ADHD-RSIV) (DuPaul, Barkley, & McMurray, 1994). Thirty of the children also met the DSM-IV-TR criteria for ODD, as established by the two tools mentioned above (DuPaul, Power, Anasopoulos, & Reid, 1998). The children were evaluated in the presence of their parents. All children attended regular school at the time of the study and all were from similar socio-economic background. All children were psychostimulant medication naïve and were referred for assessment by a paediatrician, school consultant or by the parents. The study was approved by the Maccabi Health Services Review Board for Human Clinical Studies. All participants and their parents provided consent in writing for their participation in the study after the study was explained to them. Exclusion criteria: History of organic brain syndrome, substance use, mental retardation, bipolar disorder, schizophrenia, a physical disease, delusional disorder or suicidal ideation. Diagnosis Treatment The diagnoses of DSM-IV-TR ADHD and ODD were established based on an interview with the children and their parents that was conducted by a board-certified senior child and adolescent psychiatrists and followed the guidelines of K-SADS-PL (Kaufman, Birmaher, Brent, Ryan, & Rao, 2000). The severity of ADHD was assessed by the ADHD Rating Scale (ADHD-RS-IV) (DuPaul et al., 1998). The severity of ODD was assessed by the K-SADS-PL (Kaufman et al., 2000) and was defined by the authors as ODD/K-SADS-PL score. Treatment All eligible patients received daily doses of 0.5–1.0 mg/kg of MPH – doses in the range recommended by the British Association for Psychopharmacology (Bolea-Alamanac et al., 2014). The patients were assessed by ADHD-RS-IV at baseline (day-1) and at endpoint (at the end of week 12). The daily dose did not exceed 60 mg/ day. Daily MPH doses were adjusted for all participants according to the response at the end of week 2 and at the end of week 4. The MPH formulations were MPH-IR, administered twice a day (N ¼ 15) or MPH-LA (N ¼ 26) or OROS-MPH (Concerta) (N ¼ 19) which were administered once a day. The distribution of the formulations did not differ significantly between the two groups. Throughout the study period the patients were kept off all other medications.
Measures Rating scales (1) ADHD-RS-IV (DuPaul et al., 1994): A clinician-rated, 18-item scale with one item for each of the 18 DSM-IV symptom criteria for ADHD on a severity scale of 0 (not present) to 3 (severe); overall minimal score ¼ 0 and a maximal score ¼ 54. It was used as a clinician-administered, semi-structured parent–child interview at first and last (3 month) visits to monitor ADHD symptom severity. (2) Semi-structured clinical interview of the child and the child’s parent(s) according to the guidelines of K-SADS-PL (Kaufman et al., 2000). (3) Suspiciousness Rating Scale (SRS) was especially designed for this study. This tool measures misinterpretation of social situations as being threatening. The range of this scale is 1 (not present) to 3 (severe); overall minimal score ¼ 4 and a maximal score ¼ 12. See Appendix 1. The first three questions are derived from items 34, 38 and 89 from The Child Behaviour Checklist (CBCL) (Achenbach, 1991) and are as follows: Item 1 is based on CBCL-38 Feels that others tease him/her a lot, Item 2 is based on CBCL-34 Feels that others are out to get him/her and Item 3 is based on CBCL-89 Suspicious. The last question was taken from the Conners’ Parent Rating Scale (Conners, Sitarenios, Parker, & Epstein, 1998), item 61and reads: Blames others for his/her mistakes or misbehaviour (equivalent to over-attributing hostile intentions to peers). All the questionnaires and interviews were completed during the first visit, 1 day prior to initiation of MPH treatment and again after 3 months of treatment. The trial was conducted for 12 weeks. Safety The safety of the treatment was evaluated at baseline and at endpoint. Spontaneous reports by participants on adverse effects were recorded. The spontaneous reports could be called in by telephone at any time during the study. A clinical pharmacist dispensed the medications to the patients, but the monitoring for adverse events was conducted by the psychiatric researcher (PG). Statistical analysis Two-tailed, paired and unpaired Student’s t-tests and Spearman’s correlation test were used as appropriate. Cronbach’s a test was used to assess the internal consistency for the SRS. All results are expressed as Mean ± SD and p < .05 was considered statistically significant.
Results Age and gender Sixty children and adolescents (35 boys and 25 girls), aged 12.5 ± 2.5 years were included in the study. The ADHD group aged 12.9 ± 2.5 and the ADHD/ODD group aged 11.6 ± 1.2 years. ADHD-RS-IV scores in the ADHD subjects with and without/ODD Severity of ADHD prior to treatment, as assed by the ADHD-RS-IV was significantly greater in the ADHD/ODD group (N ¼ 30) as compared to the ADHD alone group (N ¼ 30): 26.6 ± 9.9 versus 16.7 ± 10.8; paired t ¼ 3.2, df ¼ 29, p < .0034. A significant reduction in the ADHD-RS-IV scores was detected following MPH treatment in both the ADHD/ODD group (N ¼ 30; before and after: 26.6 ± 9.9 versus 19.9 ± 7.7; paired t ¼ 9.4, df ¼ 29, p < .0001) and in the ADHD group (N ¼ 30; before and after: 16.7 ± 10.8 versus 13.1 ± 8.3; paired t ¼ 3.2, df ¼ 29, p < .0034).
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Table 1. Correlations between the baseline levels and changes following methylphenidate treatment in the ADHD-RS-IV, ODD/K-SADS-PL and the SRS scores. Correlations between changes in scores following MPH treatment
Correlations in baseline scores D in Scale-Pairs ODD/K-SADS-PL with SRS (ADHD/ODD group) ODD/K-SADS-PL with SRS (ADHD group) ADHD-RS-IV with SRS (ADHD/ODD group) ADHD–RS-IV with SRS (ADHD group) ADHD-RS-IV versus ODD/KSADS-PL (ODD/ADHD Group) ADHD-RS-IV versus ODD/KSADS-PL (ADHD Group)
Spearman r
95% CI
p
Spearman r
95% CI
p
0.09 0.35 0.07 0.13 0.10 0.27
0.4 to 0.28 0.6 to 0.005 0.42–0.29 0.24–0.47 0.26 to 0.45 0.09 to 0.58
.63 .054 .69 .49 .58 .14
0.22 NA 0.48 0.21 0.19 NA
0.15 to 0.54
.24
0.14–0.72 0.54 to 0.17 0.17 to 0.52
.0066 .25 .30
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ADHD-RS-IV, ADHD Rating Scale; ADHD, attention deficit/hyperactivity disorder; ODD, oppositional defiant disorder; ODD/K-SADS-PL, ODD criteria in semi-structured clinical interviews of the child; MPH: methylphenidate; SRS: suspiciousness rating scale; NA: non-applicable (baseline ODD/K-SADS-PL were very low). Remains significant following Bonferroni correction.
ODD severity
Psychometric properties of SRS
According to the ODD/K-SADS-PL, the severity of ODD at the beginning of the study was 6.6 ± 1.4 in the ADHD/ODD group (N ¼ 30) and 3.1 ± 0.4 in the ADHD group (N ¼ 30), with unpairedt ¼13.17, df ¼ 58, p ¼ .0001. After the 12-week MPH treatment, a very modest but significant reduction improvement was found in ODD severity in the ADHD/ODD group (N ¼ 30), namely, ODD/K-SADS-PL scores for ODD dropped from 6.6 ± 1.4 at the start to 5.1 ± 1.1, (paired t ¼ 6.4, df ¼ 29, p < .0001).
The internal consistency of the SRS was found to be good, with Cronbach’s a ¼ 0.76. Excluding any item would not improve the internal consistency of this scale (corrected item total correlation for all items was 0.46). Item 1 on the SRS is based on subjective impression of being teased by others. Thus, in order to ascertain the relevance to suspiciousness of item 1 in the SRS (derived from item 89 in the CBCL), we analysed the inter-correlation coefficients between this item and the other three items on the SRS. The inter-correlation coefficients were found to be fairly good, r 0.32.
Baseline SRS scores in ADHD/ODD versus ADHD group
Safety
Significantly larger baseline SRS scores were obtained in the ADHD/ODD (N ¼ 30) group as compared to the ADHD (N ¼ 30) group (8.6 ± 2.0 versus 6.5 ± 2.1, respectively; unpaired t-test, t ¼ 3.97, df ¼ 58, p ¼ .0002).
Despite the pro-paranoid effect of stimulants (Bramness & Rognli, 2016; Kollins, 2008) both ADHD and ADHD/ODD groups displayed no signs of worsening in the level of suspiciousness and no de novo emergence of delusional/psychotic symptoms. No clinically significant complains regarding intolerable insomnia or appetite suppression were reported by the participants or their parents. Neither were there any cases of attrition from the study.
The impact of MPH treatment on SRS scores in the ADHD/ODD and ADHD groups A slight but significant reduction in the SRS scores was detected in the ADHD/ODD group (N ¼ 30) following MPH treatment (before and after: 8.6 ± 2.0 versus 7.9 ± 2.0; paired t ¼ 3.9, df ¼ 29, p < .0012). A very slight, but statistically significant, reduction in the SRS scores was also obtained in the ADHD group (N ¼ 30) following MPH treatment (before versus after: 6.5 ± 2.0 versus 6.2 ± 2.0, paired t-test ¼ 2.5, df ¼ 29, p < 0.018). Correlations between scales Baseline scores The correlations between the baseline scores of the various scales, within the ADHD/ODD and ADHD groups, are described in Table 1. As shown, no significant correlations were found between: baseline ODD/K-SADS-PL and SRS scores, baseline ODD/ K-SADS-PL and ADHD-RS-IV scores and SRS and ADHD-RS-IV scores in both the ADHD/ODD and ADHD groups. Changes in scores following MPH treatment The correlations between the changes in the ADHD-RS-IV, ODD/KSADS-PL and the SRS scores are described in Table 1. A significant correlation was found between the changes in ADHD-RS-IV and SRS scores after MPH treatment in the ADHD/ODD group but not in the ADHD group. No significant correlations were found between the changes in SRS and ODD/K-SADS-PL scores or between the changes in ADHD-RS-IV and ODD/K-SADS-PL scores in the ADHD/ODD group.
Discussion Suspiciousness The aim of the present study was to evaluate the impact of 12weeks of MPH treatment on suspiciousness in ADHD and ADHD/ ODD patients. Significantly (p ¼ .0002) larger baseline SRS scores were observed in the ADHD/ODD group (N ¼ 30) than in the ADHD (N ¼ 30) group. This finding supports our hypothesis that the severity of suspiciousness (i.e., often feeling teased, blaming others, feeling others are out to get you and feeling suspicious of others) is larger among ADHD patients with ODD than in those without ODD although even in those without ODD there is a certain level of suspiciousness. Significant reductions in suspiciousness (SRS scores) were observed after MPH treatment in both groups, probably due to the alleviation of ADHD symptoms in both groups. The neurobiological mechanism(s) involved in the anti-suspiciousness effect in ADHD with or without ODD, is(are) as yet unclear. ODD Serra-Pinheiro, Mattos, Souza, Pastura, and Gomes (2004) evaluated the effect of MPH on ODD comorbid with ADHD and reported similar findings to those of the current study, namely, improvement in ODD severity. In that study, MPH was found to be an effective treatment for ODD, as well as for the ADHD and nine of the 10 participants no longer met the diagnostic criteria for ODD after MPH treatment for their ADHD (Serra-Pinheiro et al., 2004). Sinzig, Dopfner, Lehmkuhl, Uebel, and Schmeck (2007) showed in a double-blind, randomized, 5-week clinical trial that long-
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acting MPH was effective for oppositional-defiant and aggressive behaviour, especially at school. In another study, MPH treatment was found significantly effective for oppositional symptoms in adult ADHD population, especially in patients with emotional dysregulation (Marchant, Reimherr, Robison, Olsen, & Kondo, 2011). Significant reductions in severity of SRS scores were detected in both groups following MPH treatment (before and after twotailed Student’s paired t tests: p ¼ .0012 and p ¼ .03, respectively). However, only in the ADHD/ODD group, a significant correlation was found following MPH treatment, between the improvement in ADHD, as assessed by the ADHD–RS, and the reduction in suspiciousness, as assessed by the SRS (Spearman r ¼ 0.48, p ¼ .0066). The lack of a positive correlation in the ADHD/ODD group at baseline between level of suspiciousness (SRS score) and either ODD score (ODD/K-SADS-PL/ODD score; Spearman r ¼ 0.09, p ¼ .63) or ADHD-RS-IV score (Spearman r ¼ 0.35, p ¼ .054) as well as the significant reduction of suspiciousness in both groups following MPH treatment indicate that the relationship between ODD and suspiciousness in children with ADHD is complex and merits further investigation in larger groups. Nevertheless, the results support this study’s hypothesis, that improvement in ADHD symptoms is associated with marked attenuation in suspiciousness levels in ADHD/ODD patients. The possible explanation for such simultaneous improvement may be related to a reciprocal relationship between ADHD and ODD in this sub-population (ADHD/ODD group). Recurrent ADHD/ODDrelated social disappointment, social rejection and misperception/ misrecognition of social cues in these patients may have a part in the evolution of the suspiciousness. Thus, when the severity of ADHD diminishes with MPH treatment there is a parallel attenuation in suspiciousness. MPH-related improvements in academic capacity, self-control, self-competence and self-confidence may lead to more suitable and acceptable social interactions and less social conflicts (Kats-Gold, Besser, & Priel, 2007). Similar relations were detected between poorer executive function (EF) and symptoms of ADHD and/or ODD (Skogan et al., 2014). Thus, it is possible that poor cognitive functioning in ADHD/ODD patients contributes to the emergence of suspiciousness. It is of note that Beyer von Morgenstern, Becker, and Sinzig (2014) have shown improvement of facial affect recognition in children and adolescents with ADHD when treated with MPH. Improvement in affect recognition, reward sensitivity and executive functioning (Poulton & Nanan, 2014) following MPH treatment may also play a role in reduction in suspiciousness in the ADHD/ ODD participants of the current study. Safety Both ADHD and ADHD/ODD groups displayed no signs of worsening in the level of suspiciousness and no de novo emergence of delusional/psychotic symptoms. Neither were there any cases of attrition from the study. However, the validity of the data, concerning the safety of MPH treatment in this unique population, is limited due to the relatively short duration of the study and the small sample size. Nevertheless, the findings of this study suggest that MPH treatment may be an effective intervention in ADHD/ODD children with significant levels of suspiciousness. Limitations The main limitations of this study are the open label design, the small sample size, the mild severity of the ADHD of the studied population, the relatively short treatment duration (12 weeks) and
the lack of long-term follow-up. In addition despite its good psychometric properties and reliability, there are possible limitations of the SRS. The four items of the SRS may differ in the level of the participant’s suspiciousness, ranging from feeling that others are teasing him/her (item 1), through acknowledging cognitive biases of blaming others for his/her mistakes or misbehaviour (item 4), to a general impression regarding his/her own degree of suspiciousness (item 3) and of feelings that others are out to get him/ her (item 2). The scale needs further validation in populations with more severe ADHD and ODD as well as in other pediatric psychopathologies associated with suspiciousness. Furthermore, there are some major confounding factors which may affect the results, like: the quality (or ability) of the participants’ social cognition, their level of anxiety, traumatic experiences and level of self-esteem. Moreover, since there is no group with ODD alone (without ADHD), the association between suspiciousness and ADHD þ ODD needs further validation. It should be noted that adverse events were reported by the patients or their parents with no corresponding rating scales. Thus, the data on adverse events reflect only safety and not tolerability. Additionally, there is no comparison to other anti-ADHD treatments like amphetamine, clonidine, guanfacine or atomoxetine. Still, it appears that MPH, and maybe other stimulants and nonstimulants may ameliorate suspiciousness in ADHD with and without ODD.
Conclusion This study demonstrates that MPH treatment seems to be relatively safe in ADHD/ODD patients and to diminish suspiciousness levels in this population. Furthermore, it shows that suspiciousness is higher in AHDH/ODD compared to ADHD alone and decreases following MPH treatment in both groups, indicating that suspiciousness may be considered a treatable state (versus trait). Namely, it is possible that alleviation of ADHD achieved by MPH treatment is accompanied by a corresponding relief in suspiciousness, especially in comorbid ODD. Moreover, it appears that in addition to the beneficial effect of MPH treatment in ADHD, and to some extent in ODD symptoms, it also diminishes suspiciousness in children with ADHD. These data are of clinical importance in the field of ADHD, especially in the current situation where only about half of those suffering of ADHD receive an adequate treatment despite the disabling nature of the disorder (Stuhec, 2016; Stuhec & Locatelli, 2017). However, further large-scale, double-blind, placebo-controlled studies, including 2 comparison to non-stimulants, like atomoxetine, bupropion and a adrenergic agonists (Stuhec, Munda, Svab, & Locatelli, 2015a), are required to substantiate and generalize our observations.
Acknowledgements The authors thank Dr Tomer Levi for calculating the psychometric properties of the SRS.
Disclosure statement None to declare.
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Appendix 1 Four-item suspiciousness rating scale (SRS). Scores SRS items 1. 2. 3. 4.
Feels that others tease him/her a lot Feels others are out to get him/her Suspicious Blames others for his/her mistakes or misbehaviour
Absent
Occurs sometimes
Occurs frequently
1 1 1 1
2 2 2 2
3 3 3 3
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CBCL-38 Gets teased a lot, CBCL-34 Feels others are out to get him/her and CBCL-89 Suspicious. The last question was taken from the Conners’ Parent Rating Scale (Conners et al., 1998), item 61 and reads: Blames others for his/her mistakes or misbehaviour. Suspiciousness is an equivalent of hostile attribution bias.
