Aripiprazole-Induced Acute Hiccups: A Case Report

“Mr. G,” a 62-year-old married man who had a normal birth and developmental history was hospitalized several times because of severe depression over the last 20 years. In his last admission to the outpatient unit, he had depressive symptoms unresponsive to 150 mg/day venlafaxine, 30 mg/day mirtazapine, and 10 mg/day olanzapine, and he was hospitalized to the inpatient unit. After admission, olanzapine was discontinued, and after 5 days, aripiprazole 5 mg/day was initiated. Within 2–3 hours of taking aripiprazole, the patient started having hiccups continually. The patient was examined by a neurologist and an internist. Physical examinations were normal, and blood, biochemistry, and thyroid function test results were unremarkable. Thorax and cranial CT scans and abdominal radiography demonstrated no significant findings. The hiccups were considered a probable drug reaction, so the next scheduled dose was held. Around 30 hours after the last dose, the hiccups stopped. After obtaining informed consent, aripiprazole 5 mg/day was administered again, and the hiccups were observed for only a very brief period (around 5 minutes/day). In the following 5 days, the hiccups appeared irregularly during the day, lasting for a few minutes. On day 6, the hiccups disappeared, and in his follow-up, the hiccups did not recur for a month.

Although the exact mechanism of hiccups remains undefined, both hypo- and hyperdopaminergic states and seratonergic modulation seem to be important in the development of hiccups.⁴ The central mechanism of action of aripiprazole is believed to be the stabilization of dopamine and serotonin systems through actions mainly at the D2, 5-HT1A, and 5-HT2A receptors, which may be critical in the etiopathogenesis of hiccups.⁵ There are three case reports of aripiprazole-induced hiccups in the literature.^4,6,7 In two of the cases reported, the patients had brain injuries and one patient had hyponatremia.^4,6,7 In our patient, there was no history of predisposing risk factors such as brain injury or hyponatremia.⁸ In contrast to the previous reports, in our patient, the hiccups persisted a shorter time (30 hours), and when we rechallenged with aripiprazole, the hiccups were observed for a brief period and then resolved spontaneously in 5 days. This may be related to having no concomitant medical condition. In this case, we would like to point out that benign hiccups associated with aripiprazole can resolve spontaneously without treatment and especially in the lack of predisposing factors, one should not be immediately discouraged to continue aripiprazole.