Dyskinesia in Treatment-Naive and Stimulant-Treated Children With ADHD

Abstract

Objective: Stimulants are safe and effective medications for the treatment of ADHD. There are a number of case studies that report stimulant-induced dyskinesia. The aim of this study was to compare dyskinesia in a treated and a treatment-naive group of children with ADHD, and a healthy control group. Method: Children aged 6 to 18 years were involved in the study (n = 158). Diagnosis of ADHD was measured with the Mini International Neuropsychiatric Interview Kid (MINI Kid). Dyskinesia was assessed with the Abnormal Involuntary Movement Scale (AIMS). Results: Before methylphenidate administration, the treated ADHD group showed significantly higher AIMS total score than the control group (p = .001) and the treatment-naive ADHD group (p < .001). We found the same pattern 1.5 hr after methylphenidate administration. Conclusion: These results call attention that clinicians should take special care for the possible development of dyskinesia during the treatment of their ADHD patients with methylphenidate.

Keywords

ADHD children methylphenidate stimulants

Introduction

ADHD is one of the most common psychiatric disorders in childhood and adolescence: Its prevalence is 4% to 12% among school-age children (Brown et al., 2001; Faraone, Sergeant, Gillberg, & Biederman, 2003; Polanczyk, de Lima, Horta, Biederman, & Rohde, 2007) and it persists into adulthood in 35% to 66% of cases (Biederman, Petty, Evans, Small, & Faraone, 2010; Weiss, Hechtman, Milroy, & Perlman, 1985). According to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association [APA], 2013), the core symptoms of ADHD are inattentiveness, hyperactivity, and impulsivity. The disorder is often associated with functional impairment and reduction in quality of life (Agarwal, Goldenberg, Perry, & IsHak, 2012; Dallos et al., 2017; Danckaerts et al., 2010; Velő, Keresztény, Szentiványi, & Balázs, 2013).

The treatment of ADHD contains psychoeducational, psychological, and social interventions, as well as pharmacotherapies (Faraone et al., 2015). Pharmacotherapy comprises stimulants of the central nervous system, and non-stimulants, as atomoxetine, which affects the norepinephrine system, guanfacine, and clonidine (Faraone et al., 2015). Stimulants have been used for the medication of ADHD for many decades, and since the beginning, several studies have shown that stimulants are safe and effective (Kimko, Cross, & Abernethy, 1999). The well-known stimulants are methylphenidate and dexamphetamine, with methylphenidate being the most commonly prescribed among these (Safer, 2016). Several studies indicated that stimulants have a positive short-term effect on behavioral and cognitive aspects of ADHD (Santosh & Taylor, 2000). For example, methylphenidate reduces hyperactivity and impulsivity, while it improves vigilance, learning, short-term memory, and reaction time (Kimko et al., 1999; Rapport et al., 1988).

Methylphenidate is rapidly absorbed: Its blood drug concentration reaches a peak within 1 to 3 hr (Kimko et al., 1999). The mechanism of stimulants is not yet fully understood, but may be associated with reuptake inhibition of the neurotransmitter dopamine (Volkow et al., 1999), and the norepinephrine system may be affected as well (Solanto, 1998). Stimulants increase frontal striatal activity in children with ADHD (Santosh & Taylor, 2000).

Besides the clinical effects, there are various, well-described adverse effects of stimulants as well, for example, insomnia, weight loss, decreased appetite, abdominal pain, headache, irritability, anxiety, proneness to cry, and increased heart rate and systolic and diastolic blood pressure (Barkley, McMurray, Edelbrock, & Robbins, 1990; Kelly, Rapport, & DuPaul, 1988). The adverse effects are mild, often transient, and are dependent on timing and dosage (Santosh & Taylor, 2000).

In the past few decades, and especially in recent years, an emerging number of case studies concerning the association between stimulant (mostly methylphenidate) treatment and dyskinesias have been reported (Balázs, Besnyő, & Gádoros, 2007; Case & McAndrew, 1974; Gay & Ryan, 1994; Heinrich, 2002; Hollis & Thompson, 2007; Marti, Fattinger, Zimmermann, & Exadaktylos, 2013; Mattson & Calverley, 1968; Mendhekar & Andrade, 2008; Morgan, Winter, & Wooten, 2004; Potter, John, & Coffey, 2012; Sallee, Stiller, Perel, & Everett, 1989; Senecky, Lobel, Diamond, Weitz, & Inbar, 2002; Singh, Singh, & Chusid, 1983; Thiel & Dressler, 1994; Yilmaz et al., 2013; Weiner, Nausieda, & Klawans, 1978; Willemsen & van der Wal, 2008). According to Balázs, Dallos, Keresztény, Czobor, and Gádoros (2011), these case reports can be categorized into two groups. In the first group, studies report cases in which dyskinesia arises many weeks after the first administration of the stimulant, and diminishes only months after the withdrawal of the therapy (Gay & Ryan, 1994; Mattson & Calverley, 1968; Mendhekar & Andrade, 2008; Morgan et al., 2004; Potter et al., 2012; Sallee et al., 1989; Singh et al., 1983; Thiel & Dressler, 1994; Weiner et al., 1978). The second group of studies includes cases where the emergence, and also the cessation of the dyskinesia, occurs on the same day of (or in some days following) the first administration of the stimulant (Balázs et al., 2007; Case & McAndrew, 1974; Heinrich, 2002; Hollis & Thompson, 2007; Marti et al., 2013; Mattson & Calverley, 1968; Senecky et al., 2002; Yilmaz et al., 2013; Willemsen & van der Wal, 2008).

Regarding the body area in methylphenidate induced dyskinesias, most studies reported that both the face and orofacial region (e.g., Balázs et al., 2007; Hollis & Thompson, 2007; Marti et al., 2013; Potter et al., 2012; Senecky et al., 2002; Yilmaz et al., 2013) and, in some cases, also the extremities (e.g., Balázs et al., 2007; Hollis & Thompson, 2007; Potter et al., 2012; Yilmaz et al., 2013) could be affected.

There are only few studies that investigate dyskinesia in normal sample. Magulac, Landsverk, Golshan, and Jeste (1999) found in a community sample of children and adolescents who were in foster care that one in eight children had at least one rating of “mild” movements on Abnormal Involuntary Movement Scale (AIMS). Similarly, Kindler et al. (2016) found that 12.7% of children and adolescents in a community sample had elevated level of abnormal involuntary movements, and even after dividing this group into children with and without psychosis risk, still 8.8% of children without risk for psychosis had increased level of dyskinesia. Therefore, it is very important to take into account the base prevalence of dyskinesia in healthy control sample when investigating dyskinesia among treated children. Until now, to our knowledge, only one study systematically investigated the level of dyskinesia in a group of children with ADHD treated with methylphenidate and compared them with a healthy control group of children (Balázs et al., 2011). However, in that study, no treatment-naive children with ADHD were involved; therefore, it is not clear whether the higher level of dyskinesia was due to methylphenidate treatment or to an inherent characteristic of ADHD.

The aim of our study was to investigate the extent of dyskinesia in three groups of children: a stimulant-treated ADHD group, a treatment-naive group of children with ADHD, and a healthy control group. Furthermore, we aimed to compare the body area affected by the dyskinesia in the three groups.

Method

Participants

The study was approved by the Medical Research Council Scientific and Research Committee, Budapest, Hungary. The participation was voluntary for study participants. Parents and children received both oral and written information about the study. Parents and children older than 14 years gave their written consent.

The study includes three study groups: (a) children with an ADHD diagnosis with ongoing methylphenidate treatment (hereafter: treated ADHD group), (b) children with ADHD without previous methylphenidate treatment (hereafter: treatment-naive ADHD group), and (c) healthy control children. The first two groups of children were recruited from the Vadaskert Child and Adolescent Psychiatric Hospital and Outpatient Clinic. Healthy control children were recruited from primary schools in Budapest and Szekszárd.

Inclusion criteria for the treated ADHD group were children aged 6 to 18 years, a diagnosis of ADHD according to the Mini International Neuropsychiatric Interview Kid (MINI Kid) diagnostic interview (see below), and treatment with methylphenidate.

Inclusion criteria for the treatment-naive ADHD group were children aged 6 to 18 years, a diagnosis of ADHD according to the MINI Kid diagnostic interview, and no previous methylphenidate treatment. Furthermore, we studied these children when the first dose of methylphenidate was administered to them according to the instructions of their child psychiatrist.

The inclusion criteria for the control group were children aged 6 to 18 years, no ADHD diagnosis according to the MINI Kid diagnostic interview, and no previous or ongoing psychiatric or psychological treatment.

In all three study groups, exclusion criterion was mental retardation in the medical history.

Instruments and Data Collection

The presence or the absence of ADHD was measured by the MINI Kid diagnostic interview (Balázs et al., 2004; Lecrubier et al., 1997; Sheehan et al., 1997; Sheehan et al., 1998; Sheehan et al., 2010). This diagnostic interview measures 31 psychiatric diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; APA, 1994), including ADHD. In the case of children aged younger than 13 years, both children and their parents were present for the interview. In the case of children aged 13 years or older, only the child was present at the interview. Not only ADHD but also all other psychiatric conditions were measured on the interview as well.

Dyskinesia was measured by the AIMS (Guy, 1976; Rey, Hunt, & Johnson, 1981). Beside assessing tardive dyskinesia in neuroleptic treatment, it is also used in treatment-naive or community samples (Ayehu, Shibre, Milkias, & Fekadu, 2014; Magulac et al., 1999). The raters scored the observed dyskinesias on the following areas of the body: (a) muscles for facial expression, (b) lips and perioral area, (c) jaw, (d) tongue, (e) upper extremities (arms, wrists, hands, and fingers), (f) lower extremities (legs, knees, ankles, and toes), and (g) trunk movements (neck, shoulders, and hips). The possible scores were 0 (none), 1 (minimal), 2 (mild), 3 (moderate), or 4 (severe). All children were measured with AIMS on two occasions: at T1 and T2 (90 to 120 min after). In the case of children in the treated ADHD group, T1 was just before they received the dose of methylphenidate that was prescribed for their regular treatment (normally a morning dose before going to school), and T2 was 90 to 120 min later. As described above, children in the treatment-naive ADHD group were studied at the time the first dose of methylphenidate was administered to them according to the instructions of their therapist. AIMS T1 was right before their very first methylphenidate administration, and T2 was 90 to 120 min after. In the control group, the assessment was also implemented both at T1 and at T2 (90 to 120 min after T1). Children in this group did not receive any medication. All children participated in a baseline and a provocation assessment for all body areas. At the baseline observation, the participant sat in a chair with his or her hands on his or her knees, legs slightly apart, and his or her feet flat on the floor. The tongue was observed twice when the child was asked to open his or her mouth. At the provocation assessment, the child was asked to protrude his or her tongue while tapping his or her thumb with each finger as rapidly as possible for 10 to 15 s, first with the right hand, then with the left; during this time, the tongue, face, and legs were observed. Then, the child was asked to extend both arms in front of his or her body with his or her palms down; during this time, the trunk, legs, and mouth were observed.

The MINI Kid interviews were conducted by psychologists and psychology university students, while the AIMS assessments were administered by psychiatrists. To ensure validity and inter-rater reliability, all interviewers took part in a training course on the MINI Kid and the AIMS before the study, and in persistent supervision and consultations during the study.

Statistics

The IBM SPSS Statistics Version 20 (Statistical Package for the Social Sciences [SPSS], 2011) was used for statistical analyses. For the description of the study sample, we examined the differences between the study groups applying a one-way ANOVA, or an independent samples t test with robust version when necessary for continuous variables and chi-square test for categorical variables.

Comparing comorbidities in the treatment-naive and the treated ADHD group, we created nine diagnostic categories: anxiety disorders (panic disorder, agoraphobia, separation anxiety disorder, social phobia, specific phobia, obsessive-compulsive disorder, generalized anxiety disorder), tic disorders (Tourette’s disorder; motor tic disorder, vocal tic disorder, provisional tic disorder), depressive disorders (major depressive episode, dysthymia), manic/hypomanic episode, oppositional defiant disorder/conduct disorder, trauma-related disorders (posttraumatic stress disorder, adjustment disorder), eating disorders (anorexia nervosa, bulimia nervosa), psychotic disorder, and alcohol and substance use (alcohol abuse, alcohol dependence, substance abuse, substance dependence; APA, 1994; Dallos et al., 2017). We coded whether there was at least one diagnosis or no diagnosis in each category.

Relationship between the AIMS total scores in T1 and T2 and the study groups was investigated by the generalized linear model (GLM), which is the generalization of the traditional general linear model, including ANOVA. The independent variable was the study group (i.e., control group/treatment-naive ADHD group/treated ADHD group). Potentially confounding variables such as age and gender were included as covariates in this model. This model handles categorical variables, as well as non-normally distributed variables, as our dependent variable, AIMS total score, follows a Poisson distribution (increasingly higher values are present with increasingly lower frequency) in the study sample. Bonferroni adjustment was used for the pairwise comparison of estimated marginal means.

The differences in the AIMS total scores in the different body areas between the three study groups were analyzed by GLM. Potentially confounding variables such as age and gender were included as covariates in this model.

To analyze the effect of the administration of a single dose of methylphenidate, we applied the generalized linear mixed models (GLMM), and age and gender were included as covariates in this model. The differences in the AIMS total scores in the different body areas between the three study groups were analyzed by GLM. Potentially confounding variables such as age and gender were included as covariates in this model.

A shift table was performed to investigate the changes between T1 and T2 and the raw data with the number and percentage of children who had a maximum AIMS values of 0, 1, or 2 in any body areas.

An alpha level of .05 was accepted in all analyses for statistical significance.

Results

Study Sample

The control group included 55 children (27 boys [49.1%] whose mean age was 9.99 years [SD = 2.111]). The treatment-naive ADHD group (n = 63) included 52 boys (82.5%) whose mean age was 10.28 years (SD = 2.782). In the treated ADHD group (n = 40), there were 34 boys (85.0%) whose mean age was 11.25 years (SD = 2.216).

The three study groups differed in age, F(2, 150) = 3.927, p = .023, with the control group being significantly younger than the treated ADHD group (p = .039). The study groups also differed in gender, χ²(2, 156) = 18.645; p < .001.

We did not find any significant differences between the treatment-naive ADHD group and the treated ADHD group in (a) the type of ADHD (treatment-naive ADHD group: combined type n = 43 [68.3%], inattentive type n = 17 [27.0%], and hyperactive type n = 3 [4.8%]; treated ADHD group: combined type n = 27 [67.5%], inattentive type n = 10 [25.0%], and hyperactive type n = 3 [7.5%]), (b) the number of ADHD symptoms (treatment-naive ADHD group: M = 14.16, SD = 2.789; treated ADHD group: M = 13,58, SD = 2.872), and (c) the dose per weight rate (mg/kg; treatment-naive ADHD group: M = 0.27, SD = 0.093; treated ADHD group: M = 0.25, SD = 0.087). Furthermore, we did not find any significant differences between the treatment-naive ADHD group and the treated ADHD group in comorbid psychiatric diagnoses (Table 1).

Table 1.

Comorbid Conditions in the Treatment-Naive and the Treated ADHD Groups.

Diagnostic group	At least one diagnosis present in the treatment-naive ADHD group n (%)	At least one diagnosis present in the treated ADHD group n (%)	Pearson χ²	df	p ^a
Anxiety disorders	26 (41.9)	17 (42.5)	0.003	1	.955
Tic disorders	2 (3.3)	0	1.338	1	.517
Depressive disorders	8 (12.9)	5 (12.5)	0.004	1	.952
Manic/hypomanic episode	17 (27.4)	6 (15)	2.147	1	.143
ODD/CD	41 (66.1)	19 (47.5)	3.484	1	.062
Trauma-related disorders	3 (5.1)	0	2.097	1	.270
Eating disorders	0	1 (2.5)	1.515	1	.400
Psychotic disorders	1 (1.6)	0	0.662	1	1.000
Alcohol/substance use	2 (3.3)	0	1.305	1	.519

Note. ODD = oppositional defiant disorder; CD = conduct disorder.

Fisher’s Exact Test when necessary.

Differences in the AIMS Total Scores Between the Study Groups

Figure 1 presents the AIMS total scores at T1 and T2 in the three study groups.

Figure 1.

AIMS total scores at T1 and T2 in the three study groups.

Both at T1 and T2, the three groups differed significantly in the level of dyskinesia. The overall models at T1, likelihood ratio χ²(2, 153) = 19.895; p < .001, and at T2, likelihood ratio χ²(2, 153) = 15.857; p < .001, were statistically significant and the independent variable (i.e., study group) showed also statistical significance at T1, Wald χ²(2, 153) = 21.063; p < .001, and T2, Wald χ²(2, 153) = 16.269; p < .001. At T1, the treated ADHD group showed significantly higher AIMS total score than the control group (p = .001) and the treatment-naive ADHD group (p < .001), while the control group and the treatment-naive ADHD group did not differ significantly from each other. We found the same pattern at T2: the treated ADHD group showed significantly higher AIMS total score than the control group (p = .001) and the treatment-naive ADHD group (p = .020), while the control group and the treatment-naive ADHD group did not differ from each other.

Differences in the Different Body Areas Between the Study Groups

Significant difference was found in three body areas between the study groups (Table 2 shows all body areas).

Table 2.

Differences in the Body Areas Between the Study Groups.

	Facial expression	Lips and perioral	Jaw	Tongue	Upper	Lower	Neck
Overall model
Likelihood ratio chi-square	2.060	13.229	1.810	5.198	15.947	13.699	5.390
df	2	2	2	2	2	2	2
p	.357	.001	.404	.074	<.001	.001	.068
Model effect
Wald chi-square	2.003	13.982	1.491	5.454	15.279	8.806	1.734
df	2	2	2	2	2	2	1
p	.367	.001	.475	.065	<.001	.012	.188

In lips and perioral area, there was a statistically significant difference between the three study groups (Table 2). The treated ADHD group (M = 1.15, SD = 0.170) showed significantly higher AIMS total score than the control group (M = 0.58, SD = 0.105, p = .012) and the treatment-naive ADHD group (M = 0.54, SD = 0.094, p = .005), while the control group and the treatment-naive ADHD group did not differ significantly from each other.

In upper extremities, a statistically significant difference was found between the three study groups (Table 2). The treated ADHD group (M = 0.50, SD = 0.111) showed significantly higher AIMS total score than the control group (M = 0.09, SD = 0.043, p = .002) and the treatment-naive ADHD group (M = 0.16, SD = 0.052, p = .019), while the control group and the treatment-naive ADHD group did not differ significantly from each other.

In lower extremities, there was a statistically significant difference between the three study groups (Table 2). The control group (M = 0.06, SD = 0.033) showed significantly lower AIMS total score than the treated ADHD group (M = 0.38, SD = 0.097, p = .006) and the treatment-naive ADHD group (M = 0.30, SD = 0.070, p = .006), while the treated ADHD group and the treatment-naive ADHD group did not differ significantly from each other.

Differences in the AIMS Total Scores Between T1 and T2

The AIMS total score between T1 and T2 did not differ significantly in any of the study groups, F(2, 148) = 0.774,p = .463.

A shift table shows the number and percentage of children in each study groups who had a maximum value of 0, 1, or 2 of AIMS score at any body area at T1 and T2 (Table 3).

Table 3.

Number (%) of Children Who Had a Maximum AIMS Score of 0, 1, or 2 at T1 and at T2 in Any Body Areas.

Control group
		T2
		0	1	2
T1	0	33 (86.8)	5 (13.2)	0
	1	1 (7.1)	13 (92.9)	0
	2	0	1 (33.3)	2 (66.7)
Treatment-naive ADHD group
		T2
		0	1	2
T1	0	26 (66.7)	13 (33.3)	0
	1	4 (19.0)	14 (66.7)	3 (14.3)
	2	1 (33.3)	1 (33.3)	1 (33.3)
Treated ADHD group
		T2
		0	1	2
T1	0	12 (80.0)	2 (13.3)	1 (6.7)
	1	1 (5.0)	16 (80.0)	3 (15.0)
	2	0	2 (40.0)	3 (60.0)

Note. AIMS = Abnormal Involuntary Movement Scale.

Discussion

To our knowledge, this study is the first to investigate the level of dyskinesia by comparing a stimulant-treated and a treatment-naive ADHD group of children. Although dyskinesia as a side effect of methylphenidate has been recently included in the label of medications containing methylphenidate, to our knowledge there are only a few case reports focusing on this issue. Balázs et al. (2011) investigated dyskinesia in a group of children with ADHD who were treated with methylphenidate. In this study, we extended this study design involving a treatment-naive ADHD sample as well. Our results show that the treatment-naive ADHD group did not differ significantly from the control group either before or after methylphenidate administration. However, the treated ADHD group had a significantly higher dyskinesia score than either the treatment-naive ADHD group or the control group both before and after methylphenidate administration. These results corroborate the assumption that the dyskinesia is not due to the disorder, but it may be associated with the treatment. These results also call attention to the fact that clinicians should pay special care to the possible development of dyskinesia during ADHD treatment with methylphenidate.

When examining the affected body areas, based on previous case studies, we presumed that dyskinesias would be present both in the face and orofacial regions (Balázs et al., 2007; Hollis & Thompson, 2007; Marti et al., 2013; Potter et al., 2012; Senecky et al., 2002; Yilmaz et al., 2013), and also in the extremities (Balázs et al., 2007; Hollis & Thompson, 2007; Potter et al., 2012; Yilmaz et al., 2013). When we compared the average AIMS total scores in the different body areas between the study groups, we found a significant difference in the level of dyskinesia exactly in these body areas: in the lips and perioral region; in the upper extremities, that is, in the arms, wrists, hands, and fingers; as well as in the lower extremities, that is, in the legs, knees, ankles, and toes. In case of the perioral area and the upper extremities, the control group and the treatment-naive ADHD group did not differ significantly, while the treated ADHD group showed significantly higher dyskinesia score. Interestingly, in lower extremities, we found a different pattern: The two ADHD groups did not differ from each other, while they had higher dyskinesia scores than the control group. Further studies are needed to examine this topic. While the lips/perioral areas are the most easily recognized by peers or others, this result has special clinical significance.

Based on the study of Balázs et al. (2011), we presumed that a single therapeutic dose of methylphenidate would not enhance the level of dyskinesia in children who were undergoing methylphenidate treatment. When we investigated the AIMS total scores before and after methylphenidate administration, the results of this study reinforced this assumption. Furthermore, we found the same pattern in the treatment-naive group of children with ADHD; their very first dose of methylphenidate did not cause a higher level of total dyskinesia score. However, when we investigated the changes with a shift table, we found that one quarter of treatment-naive and 15% of treated children with ADHD had a higher maximum AIMS value in any body area after methylphenidate administration than before. This result draws the attention to the importance of taking special care for the possible development of dyskinesia during the treatment of ADHD patients with methylphenidate.

As tic disorders are common comorbid conditions with ADHD (Pinto et al., 2016), it is very important to make a clear distinction between tic disorders and dyskinesia. It was reported previously that tardive dyskinesia can appear in Tourette’s Disorder (Silva, Magee, & Friedhoff, 1993). Silva et al. (1993) offered some procedures that help distinguish these two types of movement disorders. One of it is that if we apply distracting voluntary motor tasks (as we did in the provocation assessment, see above), it decreases tics but triggers dyskinesia. Moreover, patients report a subjective difference between tics and dyskinesias: premonitory urges exist in Tourette’s Disorder, but not in dyskinesia. As it is presented in Table 1, in our study, only two treatment-naive children had any type of tic disorders and no treated children had any of them, based on the MINI Kid diagnostic interview.

The limitation of our study is that it is a cross-sectional study. Although it compares a treatment-naive and a treated group of children with ADHD and thus provides new answers to the questions proposed by Balázs et al. (2011), it does not comprise the extent of dyskinesia in the same sample before treatment and after a certain period of treatment. A prospective study model following the same children as they start medication treatment and continue it would provide further knowledge in this field. Another limitation is the differences in age and gender between the control group and the ADHD groups; however, there were no significant differences between the two ADHD groups. In addition, we included these variables as covariates in our analyses. Furthermore, in this study functional impairments, such as the severity of behavior problems and IQ, were not measured, though exclusion criterion was mental retardation in the medical history. However, functional impairment and IQ may be associated with higher rates of dyskinesia, as Magulac et al. (1999) found in a community sample of neuroleptic-naive children and adolescents that lower IQ and more severe behavior problems are significant risk factors for abnormal involuntary movements measured by the AIMS.

Finally, we would like to underline the clinical implications of our study. While ADHD is a chronic condition that continues in 40% to 60% of children into adulthood (Biederman et al., 2010; Weiss et al., 1985), it requires ongoing monitoring and treatment (Brown et al., 2001). Stimulants, including methylphenidate, are the most commonly used medications (Taylor et al., 2004); therefore, it is crucial to investigate and handle their long-term adverse effects. Our study highlights the importance that clinicians should take special care for the possible development of dyskinesia during the treatment of their ADHD patients with methylphenidate, which is of special importance because dyskinesias can be seen by others, and these phenomena can be a sign of the treatment for people in the environment of the child. Therefore, treating dyskinesia when needed can prevent the stigmatization of these children.

In conclusion, our results corroborate the assumption that dyskinesia may be associated with methylphenidate treatment in ADHD. Thus, our study provides further results to the question of possible association of stimulant treatment in ADHD and dyskinesia, as raised by former case studies (e.g., Balázs et al., 2007; Marti et al., 2013; Potter et al., 2012; Yilmaz et al., 2013) and a systematic research (Balázs et al., 2011). When we compared the level of dyskinesia in the different body areas, we found a significant difference in the lips and perioral area, as well as in the arms, wrists, hands, and fingers and in the legs, knees, ankles, and toes between the study groups. However, our results suggest that these cases are rare and, in general, a single dose of this medication does not enhance the level of dyskinesia even at a subclinical level. This study—altogether with all limitations—serves as an advanced stage compared with previous research in this field. Moreover, it highlights the importance of further studies revealing more aspects that are now still unclear.

Footnotes

Acknowledgements

The authors thank Ms. Margit Kovács and Dr. Gergely Mészáros for their help in the data collection. They also thank Ms. Johanna Takács for her help in the statistical analysis.

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Judit Balazs, MD, PhD, is advisor of Eli Lilly company from 2014. At the time of the data collection, she did not have anything to disclose.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was partly supported by OTKA K108336 Grant. Judit Balázs was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.

Author Biographies

Ágnes Keresztény is an assistant lecturer psychologist in the Eötvös Loránd University, Budapest, Hungary. She is going to complete her PhD studies in 2017 in Semmelweis University, Budapest, Hungary, her supervisor is Judit Balázs. Her PhD topic is based on this paper: dyskinesia in children with ADHD.

Gyöngyvér Ferenczi-Dallos is a child psychiatrist in the Vadaskert Child Psychiatry Hospital, Budapest, Hungary, her supervisor was Judit Balázs. She finalized her PhD studies in 2015 in the Semmelweis University, Budapest, Hungary. Her topic was quality of life of children with ADHD and subthreshold ADHD.

Szabina Velő is a psychology PhD student in the Institute of Psychology, Eötvös Loránd University, School of PhD, Budapest, Hungary, her supervisor is Judit Balázs. Her topic is quality of life of children with ADHD.

Júlia Gádoros is a child psychiatrist in the Vadaskert Child Psychiatry Hospital, Budapest, Hungary. She established this hospital in 2003, which is currently the largest child psychiatric institution in Hungary.

Judit Balazs is a child psychiatrist, her research areas are ADHD, quality of life, subthreshold disorders and suicidology. She is the Chair of the Department of Developmental and Clinical Child Psychology of Institute of Psychology, Eötvös Loránd University, Budapest, Hungary and the Director for education and research in Vadaskert Child Psychiatric Hospital, Budapest, Hungary.

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