Letter: A Rare Case of Dose-Dependent Priapism in a Child with Autism Treated with Aripiprazole and Risperidone

To the Editor:

This article presents the case of a 7-year-old male diagnosed with autism spectrum disorder (ASD) who developed priapism after the dose of aripiprazole was increased while continuing the ongoing risperidone regimen at the same dose. To the best of our knowledge, this is the first reported case of priapism occurring in a child receiving both aripiprazole and risperidone and the second case of priapism linked to aripiprazole use in the pediatric population.

The patient had been on 1 mg/day of risperidone for several months and was prescribed 0.5 mg/day of aripiprazole in addition to risperidone due to persistent symptoms of hyperactivity, irritability, and aggression. One month later, at a follow-up visit, the parents reported partial symptom improvement without any side effects. However, after increasing the aripiprazole dose to 1 mg/day, the patient experienced priapism attacks lasting approximately 30 minutes, which resolved spontaneously. Informed consent was obtained from the guardian for this case report.

The patient’s medical history revealed that at age 5, while on aripiprazole alone, he had experienced priapism, which resolved upon dose reduction. There were no other known medical conditions or medications and no signs of trauma, hematological disorders, or drug–drug interactions. Due to the recurrence of priapism following the dose increase, aripiprazole was considered a likely cause. Reducing the dose to 0.5 mg/day led to the cessation of priapism attacks. Although the patient was also on risperidone, we did not identify any clinically significant drug–drug interaction between risperidone and aripiprazole that would suggest it as the primary cause of priapism. The patient had previously experienced priapism while on aripiprazole alone, which further supported our attribution of the side effect to aripiprazole. The combination of risperidone and aripiprazole may have had an effect, but given that priapism is dose-dependent on aripiprazole and given the patient’s past experience, aripiprazole seems to be the more likely factor. The Naranjo Adverse Drug Reaction Probability Scale assigned a score of 10, confirming aripiprazole as the likely cause of priapism in this case (Naranjo et al., 1981).

Priapism is a rare side effect of antipsychotics, typically seen in adults (Andersohn et al., 2010). Drug-induced priapism accounts for approximately 30% of cases, with over 50% attributed to antipsychotic medications (Brichart et al., 2008). While the exact mechanism is not fully understood, it is believed that aripiprazole’s antagonistic effects on alpha-1 adrenergic receptors lead to blockade in the corpus cavernosa, resulting in arteriodilation and inhibition of the sympathetic nervous system, which may cause priapism (Sood et al., 2008). Antipsychotics vary in their affinity for alpha-1 adrenergic receptors, and those with a higher affinity are more likely to induce priapism (Andersohn et al., 2010). Despite aripiprazole’s low affinity for alpha-1 receptors compared with other atypical antipsychotics, priapism occurred in this case, suggesting additional mechanisms beyond alpha-1 receptor blockade may be involved.

Aripiprazole’s effects on dopamine D2 and serotonin 5-HT2A receptors could contribute to priapism through vascular regulation. Its complex interactions with neurotransmitters such as dopamine, norepinephrine, and serotonin could lead to varying neurological responses. Its partial agonist effect on dopamine D2 receptors may be associated with mechanisms affecting both cerebral and peripheral blood vessels. Additionally, its impact on serotonin 5-HT2A receptors can lead to vasodilation, further increasing the risk of priapism.

Patients with ASD may be more sensitive to medication side effects, which could increase the likelihood of rare adverse reactions such as priapism.

Genetic factors, such as polymorphisms in the alpha-1 adrenergic receptor or cytochrome P450 enzymes, may influence aripiprazole’s metabolism and pharmacological response (Yoshida and Müller, 2020), increasing susceptibility to priapism. Pharmacogenetic research is crucial to understand why some individuals experience side effects like priapism.

Given the rarity of priapism in children, additional studies are necessary to understand the underlying mechanisms and genetic factors contributing to antipsychotic-induced priapism in pediatric patients. Specifically, research into cytochrome P450 enzyme polymorphisms and neurotransmitter pathways may shed light on why some individuals are more prone to these rare adverse effects.

This case emphasizes the need for caution when prescribing aripiprazole, particularly in combination with other medications.