The Relationship between Acute Dyskinesia with a Single Dose of Methylphenidate and Recent Risperidone Discontinuation in a Child with Attention-Deficit/Hyperactivity Disorder

To The Editor:

Risperidone is widely accepted as being beneficial in childhood psychiatric disorders with disruptive behavioral symptoms, even with comorbid attention-deficit/hyperactivity disorder (Sabuncuoglu 2007). In addition, risperidone in combination with a psychostimulant is reported to be effective and safe without any increment in unwanted effects in children with a subaverage intelligence quotient (IQ) who have disruptive behavioral and/or attention problems (Aman et al. 2004).

Two types of dyskinesia are described, according to the duration of onset after the first introduction of methylphenidate (MPH) treatment in children. Dyskinesic symptoms that occur after several weeks (Lipkin et al. 1994) or acute symptoms that occur within hours (Senecky et al. 2002) after MPH administration may subside completely in the same day after cessation of MPH (Balazs et al. 2007). Waugh (2013) proposed that dyskinesia is related with MPH add-on treatment in children with behavioral problems who were under chronic antipsychotic or valproate treatment (Waugh 2013). In addition, switching from an antipsychotic drug to MPH is also attributed as a cause of dyskinesia in several case reports (Hollis and Thompson 2007; Sabuncuoglu 2007).

Here, we report an acute development of dyskinesia after the first introduction of MPH in a boy with risperidone withdrawal who was under valproate treatment.

Case Report

A 6-year-old boy who was born at the 38th week of gestation by normal spontaneous vaginal delivery, showed delayed development in expressive language, whereas development of motors skills was in the normal range. He was living with his parents and a younger brother. None of whom had delayed speech or movement disorders.

When he was 5 years old, he was referred by his pediatrician to a child and adolescent psychiatry outpatient clinic because of speech delay. His parents stated that he displayed difficulty in attention, and exhibited behavioral problems such as hitting his parents, and kicking and punching the walls. During examination, he was able to use ∼25 words and to respond to simple commands, but had limited eye contact and motor tics in his hands. He was sent to a pediatric neurology department because of his blank stare, brief upward rotation of the eyes, and unresponsiveness for a few seconds. His awakening electroencephalogram (EEG) was normal and his sleeping EEG revealed widespread irregular slow wave paroxysms with short intervals in both hemispheres. He was diagnosed with epilepsy, and treatment with valproate 100 mg twice a day was initiated.

Only language skills and social understanding were below average on psychological testing by the Brunet–Lezine R Scale. His Autism Diagnostic Interview-Revised scores were not high, and a hearing test was rated as normal. Diagnosis of expressive language disorder was “offered” according to Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (American Psychiatric Association 2013). After 6 months of speech therapy and frequent interviews with parents and child, the boy's speech-related symptoms were improved, he could make eye contact, and he had better social skills; however, his behavioral problems remained. He showed conduct problems and hyperactivity in his nursery class and he was inattentive to tasks and unable to remain focused on the same topic for any length of time. He was started on risperidone 0.25 mg/day because of his behavioral problems and motor tics, and was titrated up to 1 mg/day over 6 weeks.

As his inattentiveness and hyperactivity remained after 3 months, we recommended a switch from risperidone to methylphenidate, with 5 mg/day as an initial dose. There were 4 drug-free days between these two regimens. Three hours after taking the first dose of MPH 5 mg, the patient was admitted to a psychiatric emergency unit with prominent distress caused by involuntary jaw movements, tongue rolling, and repetitive chewing-like behaviors. He also showed irregular, counting-like movements of the fingers and serial blinking. Total Abnormal Involuntary Movement Scale (AIMS) score was 20 points. He was taken for observation in the emergency unit without any intervention. Dyskinesic symptoms gradually diminished over 3 hours and the AIMS score was 8 points before discharge. The patient was symptom free by morning and at a follow-up visit 1 month later.

Discussion

In the current case, 5 mg/day MPH was initiated 4 days after risperidone discontinuation. The patient had been receiving risperidone 1 mg/day for 3 months, which had been tapered off within 2 weeks. In line with our case report, in the literature, several case reports show development of acute dyskinesia after the first dose of MPH, taken after switching from risperidone in children with ADHD or behavioral problems (Hollis and Thompson 2007; Sabuncuoglu 2007). Including in our case, the acute dyskinesic symptoms were quickly resolved after discontinuing the MPH treatment regimen, which is evidence against the proposal that dyskinesia might be caused by risperidone withdrawal (Hollis and Thompson 2007; Sabuncuoglu 2007). Furthermore, motor tics were present in our case, and the relationship between motor tics and basal ganglia is a well-known fact. The atypical antipsychotic drugs upregulate dopaminergic receptors (Silvestri et al. 2000), whereas MPH corresponds to downregulation of dopamine receptors and of dopamine transporters in the striatal system (Vles et al. 2003), which may be related with the basal ganglia sensitivity theory in children, who are more vulnerable to the side effects of MPH (Connor 1998). In addition to clinical case reports, a recent study was published about the relationship between MPH use and provocation of dyskinesia in children with chronic MPH use and healthy controls. In this study, no relationship between single-dose MPH use and dyskinesia was reported (Balazs et al. 2011). However, the study's conclusion should be interpreted cautiously, because all the children had been receiving MPH for a long time.

With the occurrence of rapid and severe dyskinesia symptoms after MPH as add-on therapy to sodium valproate in two children with ADHD and comorbid epilepsy, Gara and Roberts were not in favor of combining MPH and sodium valproate (Gara and Roberts 2000). In accordance with the literature, our patient had also been taking sodium valproate 200 mg/day for epilepsy for ∼1 year.

Therefore, when tapering off an antipsychotic drug slowly, one must keep in mind that there is a need for a drug-free interval while planning to prescribe MPH for patients with ADHD who have predisposing factors for unwanted side effects such as comorbid neuropsychiatric illnesses (i.e., motor tics, epilepsy) and chronic use of sodium valproate.