Dexmethylphenidate Extended Release-Associated Orofacial Dyskinesia in an Adolescent with Autism Spectrum Disorder After Prolonged Use

To the Editor:

Orofacial dyskinesias are involuntary repetitive movements of the mouth and face, which are commonly seen among patients who receive long-term treatment with antipsychotic drugs. This condition has also been reported with antidepressants, mood stabilizers, anticonvulsants, antiemetics, and many other medications (Correll et al. 2017.). Described herein is an unusual case of an adolescent female who developed orofacial dyskinesia associated with dexmethylphenidate extended release (DMPH-ER), despite previously tolerating the medication well for >3 years.

Discussion

There are limited reports in the literature about CNS stimulant (more superficially with immediate release methylphenidate, dexedrine, and dexamphetamine)-induced orofacial dyskinesia (Balázs et al. 2007, Yilmaz et al. 2013). To the best of our knowledge, this is the first case of extended release (DMPH-ER) preparation-induced orofacial dyskinesia. In contrast to previously reported cases wherein dyskinetic movements occur shortly after starting CNS stimulants and rapidly disappear after discontinuing the drugs (Yilmaz et al. 2013), our case of dyskinetic movements started after the patient had tolerated DMPH-ER 25 mg for an extended period of time.

In developing a plan of care, and in reviewing the literature, we carefully considered several other possible etiologies for the reported symptom. However, the dyskinesia lasted until the afternoon when symptomatic effects of DMPH-ER tend to fade, and given the rapid resolution of symptoms after discontinuing DMPH-ER, as well as finding no compelling evidence of other etiologies, we concluded that the orofacial dyskinesia was associated with the DMPH-ER.

One other possibility includes motor tic disorder. The temporal relationship with the morning dose and lack of history of tics makes the likelihood of tic disorder as an alternate etiology very low. Currently, the Food and Drug Administration requires the package inserts of psychostimulant medications to list a family history of Tourette's syndrome or the presence of a tic disorder as a contraindication. Meta-analysis in children with ADHD and comorbid tics demonstrated that MPH, alpha-2 agonists, and atomoxetine have shown efficacy in treating ADHD symptoms without worsening tics severity (Bloch et al. 2009). In a small crossover study, supratherapeutic doses of dextroamphetamine (1.28 mg/kg per day) worsened tic severity (Castellanos et al. 1997).

The possibility of sensitization of the dopamine receptor associated with discontinuation of risperidone (withdrawal-emergent dyskinesia) cannot be completely ruled out in this case; however, it would seem to be an unlikely cause due to lack of emergence of orofacial dyskinesia during the 4-month interval of risperidone discontinuation.

In this case, there was emergence of orofacial dyskinesia with a higher dose of DMPH-ER (25 mg) after being on this dose for 5 months, but subsequently, the patient was able to tolerate the low dose of MPH-IR (10 mg total daily dose) without emergence of abnormal movements. These two preparations differ in the blood level and duration of action, which could explain why the 5 mg MPH-IR dose was tolerable when the DMPH-ER 25 mg dose was not. In addition, in rodent studies, d-MPH and l-MPH isomers differed in receptor affinity to monoamine transporters (Markowitz et al. 2006), and the l-MPH isomer also inhibited the locomotor stimulation by d-MPH in a dose-dependent manner (Baldessarini and Cambell 2001).

This may further explain variable tolerability of these two preparations. This case highlights the importance of judicious dosing as well as continuous monitoring for the emergence of abnormal movement disorders with CNS stimulants, especially when there is a family history of these events, and even if the patient has tolerated medication for a prolonged period of time.