Cessation of Nocturnal Enuresis with Aripiprazole

To The Editor:

Aripiprazole is a partial agonist at the dopamine D2 and serotonin 5-HT1A receptors and an antagonist at the serotonin 5-HT2A receptors. It also has a low affinity to the adrenergic α1, histamine H1, and muscarinic receptors. Several studies have reported that it was effective for irritability, aggression, self-injurious behaviors, and hyperactivity in children with intellectual disability and autistic spectrum disorder. The most reported adverse effects include fatigue, increased appetite, headache, sedation, somnolence, and nausea (Owen et al. 2009; Deb et al. 2014).

Enuresis was reported as a rare side effect of aripiprazole (Karakurt and Suren 2015). In an 8-week double-blind randomized controlled study, although the frequency between groups before the trial is not known, frequency of enuresis in the aripiprazole group was lower than the placebo group after initiating treatment (6.4% vs. 8%) (Owen et al. 2009). Herein, we report cessation of enuresis with aripiprazole in a child with intellectual disability.

Case Report

A 9-year-old boy with a diagnosis of intellectual disability was admitted to the child and adolescent psychiatry out-patient clinic by his mother with complaints of hyperactivity, irritability, aggressiveness toward his parents, and self-injury behaviors (head banging and finger beating). According to his mother, these symptoms were evident for 3 years and several pharmacological agents were initiated, but he did not continue because of their severe side effects. He developed akathisia with olanzapine, hypersalivation with risperidone, dystonia with zuclopenthixol, and excessive anxiety with methylphenidate. He also had nocturnal enuresis four to five times a week. According to his mother's report, he did not remain dry for more than a week at any time in his life. His medical workup was unremarkable for his enuresis and he was not receiving any medication.

We decided to start aripiprazole 2.5 mg/day for his disruptive behaviors and increase the dose to 2.5 mg twice daily within 2 weeks. In the second visit, 4 weeks after, his mother reported that his disruptive behaviors improved. His mother also reported that his nocturnal enuresis reduced dramatically after the initiation of aripiprazole, which occurred with a frequency of two times during 4 weeks. To understand the possible association between cessation of enuresis and aripiprazole, we stopped the medication. His enuresis reemerged with a frequency of 7 nights during 10 days. We then restarted aripiprazole treatment and his enuresis ceased.

Discussion

We presented a pediatric case with enuresis that ceased after initiation of aripiprazole. Recurrence of enuresis after discontinuation and improvement upon readministration suggest aripiprazole to be the causally responsible agent in the cessation of enuresis. To our knowledge, this is the first reported case of a child with enuresis remitted with aripiprazole administration.

Enuresis was suggested to be occurring in a hypodopaminergic state in the basal ganglia (Ambrosini 1984; Hergüner and Mukaddes 2007) and it was reported that dopamine agonists improve enuresis (Williamson et al. 2011). Lee and Kim (2010) described cessation of clozapine-induced enuresis with aripiprazole augmentation in two adults with schizophrenia. We may suggest that, as a dopamine partial agonist, aripiprazole improved the enuresis by increasing dopaminergic transmission in the central pathways that control micturition reflex.

Alpha1-adrenergic receptors promote the contraction of the bladder neck and urethra. It was suggested that dopamine activates alpha1-adrenergic receptors and inhibits nocturnal enuresis by improving the sphincter tone (Lei 2014). The 5-HT1A receptors also play a role in controlling bladder contractions and micturition (Ramage 2006; Hergüner et al. 2007). In this case, cessation of enuresis might be because of aripiprazole's partial agonist effect at the 5-HT1A receptors as well.

We reported cessation of enuresis with aripiprazole in a pediatric case. Further research is needed to determine the antienuretic effects of aripiprazole.