Functional Vomiting Treated Successfully with Aripiprazole in a Child with Autism Spectrum Disorder

To The Editor:

Autism spectrum disorder (ASD) is defined by deficits in social communication and interaction, as well as by restricted and repetitive patterns of behaviors and activities. In addition to these core symptoms, children with ASD may present with medical conditions, including gastrointestinal dysfunctions. Several studies showed that children with ASD had higher rates of gastrointestinal problems than typically developing controls, such as constipation, diarrhea, bloating, reflux, and vomiting (Kang et al. 2014).

Functional vomiting (FV) is defined as vomiting in the absence of gastrointestinal or central nervous system or metabolic diseases. Several pharmacological agents, such as antipsychotics (e.g., chlorpromazine) (Ozdemir et al. 2014), and antidepressants (e.g., mirtazapine) (Coskun and Alyanak 2011) have been reported to be efficient in management of FV. In this report, we describe a child with ASD who had frequent episodes of vomiting that improved after aripiprazole administration.

Case Report

A 6-year-old boy with a diagnosis of ASD was referred to our outpatient clinic because of his disruptive behaviors, including hyperactivity, temper tantrums, and irritability. According to his parents, he had also had frequent vomiting episodes, occurring once or twice every day for the past 3 years. His physical examination and diagnostic tests, including endoscopy, were unremarkable. He was diagnosed as having functional vomiting by his gastroenterologist. Risperidone 0.5 mg was initiated for his disruptive behaviors, and the dose was titrated up to 1 mg/day, but no improvement was observed during a 3 month period. Then it was decided to change risperidone to aripiprazole, and the dose was increased to 5 mg/day for a 1 month period. According to the patient's parents, his hyperactivity and irritability did not improve; however, his vomiting episodes remitted completely. He was on this regime for 6 months, and during this time he did not experience any vomiting episode. Six months later, his parents stopped aripiprazole by themselves, as the boy's disruptive behaviors did not improve significantly. However, his vomiting episodes recurred after cessation of aripiprazole. Subsequently, his parents restarted aripiprazole 1 mg/day, and the patient was free of vomiting for 3 months.

Discussion

In this report, we described a patient with ASD who had frequent vomiting episodes and had a marked and rapid improvement following aripiprazole. The chronological relationship between the time of aripiprazole administration and reduction in vomiting in the absence of an identifiable medical condition suggests that aripiprazole was responsible for cessation of vomiting. Although it was found to be useful in reducing morphine-induced emesis in animals (Shiokawa et al. 2007), to our knowledge, this is the first report of successful treatment of FV with aripiprazole.

Various receptors, transmitters, and neuronal pathways are involved in the process of vomiting. Histamine, vasopressin, neurokin, serotonin, and dopamine have been suggested as neurotransmitters that are involved in the initiation or/and maintenance of vomiting. There are several classes of agents that antagonize receptors involved in the pathophysiology of vomiting, such as dopamine antagonists (e.g., chlorpromazine and haloperidol), serotonin antagonists (e.g. ondansetron), antihistamines, and anticholinergics, which have been reported to be effective in the treatment of vomiting (Tan et al. 2014).

Aripiprazole has been approved by the Food and Drug Administration for the treatment of irritability associated with ASD. It is a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and is an antagonist at serotonin 5-HT2 receptors. Aripiprazole also exhibits high affinity for dopamine D3 receptors, moderate affinity for dopamine D4, serotonin 5-HT2C, serotonin 5-HT7, α-1 adrenergic, and histamine H1 receptors (Deb et al. 2014). We suggest that the antagonistic effect of aripiprazole on dopamine, serotonin, and histamine receptors might be the cause of vomiting cessation.

This case suggests that aripiprazole may be effective in treatment of children with FV. Further research about the efficacy and safety of aripiprazole in this group is warranted.