A descriptive study of aripiprazole, brexpiprazole, and cariprazine exposures in children ages 0 to 5 years reported to United States poison centers

Brexpiprazole toxicity in a paediatric patient

“…This case and available research on antipsychotics allows for a comparison between brexpiprazole and similar antipsychotics, such as aripiprazole and cariprazine. These medications, termed ‘third generation antipsychotics’, have the additional mechanism of partial agonist activity at postsynaptic D 2 receptors 3. The research on third-generation atypical antipsychotics provides insight into the similarities and differences between the clinical outcomes, treatments, mechanisms of action and symptoms.…”

“…The research on third-generation atypical antipsychotics provides insight into the similarities and differences between the clinical outcomes, treatments, mechanisms of action and symptoms. Leading theories on the delayed onset of symptoms include partial agonism, functional selectivity at target receptors or the selective metabolism leading to a prolonged elimination half life 3. Due to brexpiprazole’s metabolism by CYP3A4 and CYP2D6 enzymes, medications and conditions that affect these enzymes also affect the presentation of brexpiprazole overdoses.…”

“…Brexpiprazole toxicity in children is not yet widely studied or understood but can potentially lead to musculoskeletal, cardiac and neurological symptoms 3 9. In cases of third-generation antipsychotic ingestion within the paediatric population, there should be a high level of suspicion for toxicity with delayed-onset symptoms.…”

“…With an elimination half life around 91 hours (about 4 days), brexpiprazole is primarily metabolised by CYP2D6 and CYP3A4. It is excreted through urine and faeces, and its serum concentrations are unaffected by hepatic or renal impairment 1 3. Common side effects of exposure to third-generation antipsychotics, such as aripiprazole, include central nervous system depression, tremors, tachycardia, QTc prolongation and vomiting 2 4.…”

“…As a relatively new antipsychotic, brexpiprazole is not yet approved by the Food and Drug Administration for use in children. With minimal research on the effects of brexpiprazole in children,1 3 5 6 the manifestations of its toxicity are not well established. This case demonstrates delayed-onset toxicity symptoms with brexpiprazole exposure in early childhood.…”