Risperidone-Induced Paroxysmal Perceptual Alteration in a Child with Autism

To the Editor:

A ntipsychotics have been reported to induce recurrent brief episodes of visual hypersensitivity known as paroxysmal perceptual alteration (PPA) (Praharaj et al. 2008). The prevalence rate of PPA is found to be 3–4%, and higher with high-potency antipsychotic drugs than with low-potency ones (Uchida et al. 2003). Because almost all patients with PPA are diagnosed with schizophrenia, PPA is often mistakenly considered as a schizophrenic symptom. Further, all patients with PPA are reported to be in the adult age group (Uchida et al. 2006; Nakajima et al. 2009).

Risperidone, an atypical antipsychotic, is being widely used in treating behavioral problems of children with autism. Here we present a case of risperidone-induced PPA in a child with autistic disorder. To our knowledge, this report is the first case of PPA in autism spectrum disorders and also the first report in the pediatric population.

Case Report

BS, an 8-year-old boy, was referred to our outpatient unit by his parents because of aggression, irritability, and self-injurious behaviors. He had temper tantrums and low frustration tolerance. He also engaged in deliberate hand-biting, especially when frustrated. These behavioral problems had started 3 months before referral. Information regarding his developmental and psychiatric history was taken from his mother. According to her, he had been diagnosed with autistic disorder when he was 3 years of age. He was said to have inappropriate peer relations, a lack of emotional reciprocity, and a marked difficulty in the ability to initiate conversation. He also used repetitive language and did not engage in appropriate social play, with stereotypies and motor mannerisms such as hand flapping and body rocking. There was no evidence of physical disorders, and his medical workup was unremarkable. He was enrolled in a special educational program. He showed some improvements in social responsiveness and language development. He was a well-adjusted child with diagnosis of autistic disorder at the age of 6 years. He was able to conduct a simple conversation spontaneously.

However, risperidone was initiated at 0.5 mg/day to cope with his recent behavioral problems (e.g., temper tantrums, hand biting, irritability). A week after introducing risperidone, his parents reported that he had started to experience recurrent episodes of terrifying visual hallucinations. They stated that he had never experienced these visual alterations before and that he described the episodes to his family as follows:

“I see large black spots on the wall. The objects are lighting everywhere and the curtains are on fire.”

His parents ceased the treatment because of these episodes. After risperidone was stopped, he never experienced visual alterations. However, his behavioral problems re-emerged and his parents told us that they had decided to restart the treatment because he benefited from risperidone and his behavioral symptoms resolved substantially. However, he experienced the same episodes soon after using risperidone. As these episodes terrified him and his parents, they had to stop the medication and consulted us again.

There was no significant finding on neurologic and ophthalmologic examination, electroencephalography, magnetic resonance imaging, and blood work. There were also no symptoms of extrapyramidal side effects during the psychiatric evaluation at the second visit.

Discussion

We reported the case of an autistic child who developed PPA after starting risperidone and had rapid remission after the discontinuation of the drug. To us, this is the first report of an antipsychotic-induced PPA in an autistic patient and also the first report in a child. The literature on PPA is limited to case reports, and PPA is reported to occur in adults with schizophrenia and nonschizophrenic diagnoses such as mood and anxiety disorders, who are taking antipsychotic agents. First generation antipsychotics are more likely to induce PPA than are second generation ones (Uchida et al. 2003). PPA here seems to be related to low dose risperidone, an atypical antipsychotic, in a child with autism.

With medical examinations and neuroimaging methods, we excluded the possible organic conditions that may cause visual hallucinations. As visual alterations are also associated with other psychiatric disorders such as psychosis, mood and anxiety disorders, and delirium, we comprehensively questioned the patient about these disorders and especially questioned his parents and teachers. Our patient had never experienced PPA before and PPA occurred with risperidone treatment and disappeared soon after ceasing the drug. That his parents unconsciously applied the challenge–dechallenge–rechallenge method, a medical testing protocol, also demonstrates us that risperidone was responsible for PPA in our case. PPA is reported to occur with extrapyramidal symptoms such as oculogyric crisis (OGC) simultaneously in the literature (Uchida et al. 2003, 2006). We did not find any symptom related to the extrapyramidal system during psychiatric examination, and the patient's parents also did not complain about any symptoms other than PPA.

Given previous and present reports that have shown a close relationship between PPA and OGC, dopamine antagonism is held responsible for PPA, and potential mechanisms may be described, considering the similarities between PPA and OGC. Risperidone that induced PPA in this case blocked D2 receptors and serotonin 5-HT2 receptors. The basal ganglia are expected to play an important role in the pathogenesis (Borison and Diamond 1987). Apart from their function in motor control, the basal ganglia are also involved in emotions such as anxiety and arousal through their network (Afifi 2003). Dopaminergic imbalance caused by antipsychotics may result in an increase in the arousal and anxiety level, inducing visual hypersensitivity and dysphoric sensations. That may lead to PPA as a sensory symptom and extrapyramidal side effects such as motor symptoms (Uchida et al. 2006). The other explanation for PPA is about contrast sensitivity (Bodis-Wollner 1990). Dopamine receptor antagonists have been hypothesized to induce dopaminergic imbalance in the retina and visual cortex (Masson et al. 1993). More research is needed to address the pathophysiology of PPA with the previously mentioned findings.

PPA is frequently misdiagnosed as a sign of exacerbation of the underlying disorder because of its psychosis-like symptoms, and clinicians tend to increase the dosage of the antipsychotic agents, which in turn worsens PPA. Our patient substantially benefited from risperidone and PPA here was not perceived as a sign of the present condition. The proper treatment strategy for PPA is the discontinuation of antipsychotic, which the family unconsciously did here. That PPA occurred with low-dose risperidone in our case is also surprising. There is also a case report of PPA in a woman with depression taking low-dose risperidone (Pariwatcharakul and Ketumarn 2009).

It is well known that the pediatric population, especially children with pervasive developmental disorders (PDD) and mental retardation (MR), is more susceptible to the side effects of psychotropic drugs. Given the widespread use of antipsychotics in children, the unusual side effects of these drugs, such as PPA, as well as common ones such as weight gain and sedation, should be borne in mind while using them in this population, especially in children with PDD and MR, irrespective of psychiatric diagnosis.