Extrapyramidal Symptoms as a Result of Risperidone Discontinuation During Combination Therapy with Methylphenidate in a Pediatric Patient

To The Editor:

Risperidone is a second-generation antipsychotic used in the treatment of schizophrenia and disruptive behaviors in adolescents and young adults. Although extrapyramidal symptoms (EPS) are a known complication of psychotropic use, they are not an expected side effect of psychotropic discontinuation. To our knowledge, this is the first case that describes the acute onset of EPS as a result of discontinuation of risperidone during combination therapy with methylphenidate in a pediatric patient.

Case Report

C.G. was a 13-year-old boy with a psychiatric history of schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder (ADHD), and autism who was responsive to risperidone, oxcarbazepine, and methylphenidate. His medical and family histories were noncontributory. Risperidone was started at age 4 for aggressive behavior and titrated to 1.5 mg b.i.d.

A few months prior to presentation, he experienced significant weight gain and a decision was made to taper risperidone and start quetiapine instead. When risperidone was at a dose of 0.5 mg b.i.d., the patient developed a severe, painful cervical dystonia and dyskinesia consisting of intense, repetitive, involuntary movements of the upper extremities, as well as an uncontrollable sense of restlessness and agitation. The patient had never had any symptoms of dystonia, akathisia, or tardive dyskinesia.

Quetiapine was increased to 300 mg t.i.d. with minimal improvement after 3 weeks. The patient was also treated with diphenhydramine 50 mg t.i.d., benztropine 2 mg t.i.d., clonidine 0.2 mg b.i.d., and lorazepam 2 mg t.i.d., but his symptoms continued to worsen. Risperidone was reinstated at a dose of 0.5 mg b.i.d. and increased to his previous dose of 1.5 mg b.i.d. within 3 days, after which the dystonia, akathisia, and tardive dyskinesia resolved.

Discussion

EPS can occur when a neuroleptic is removed from a drug regimen that includes a psychostimulant, as suggested by the present case. A few case reports have described a similar side effect following the discontinuation of methylphenidate from a drug regimen with risperidone (Keshen and Carandang 2007; Guler et al. 2015), with concomitant use of amphetamine and aripiprazole (Hollis and Thompson 2007), as well as following the administration of methylphenidate in a patient who had recently stopped taking risperidone (Shen 2008).

Taken together, these observations raise the possibility that the combination of a psychostimulant with an atypical antipsychotic can, in and of itself, increase the risk of EPS in vulnerable individuals, regardless of the order in which either agent is introduced or discontinued. The precise mechanism underlying the manifestation of EPS in this setting remains unclear. One possibility is that risperidone-induced dopamine receptor antagonism may result in upregulation of dopamine receptors leading to dopamine hypersensitivity. Increased amounts of dopamine in the synaptic cleft from methylphenidate use may then trigger the development of EPS in some cases. However, further studies are required to elucidate the precise mechanism(s) involved.

Clinicians should be cognizant of the increased risk of this adverse effect in children and adolescents treated with a combination of these drugs, and utmost care must be taken when switching, initiating, or discontinuing either of these agents. When EPS do not respond to anticholinergic therapy, prompt reestablishment of the patient's previous drug regimen is recommended to avoid the risk of long-term complications.