Aripiprazole-Induced Persistent Hiccups in an Adult With Drug-Induced Psychosis

Hiccups are a distressing symptom that can arise from multiple underlying causes, including medication.¹ Hiccups have been reported to be a rare side effect of antipsychotic medications. There are reports of hiccups associated with aripiprazole, risperidone, clozapine, and amisulpride.^2–6 In a recent review of literature on hiccups associated with aripiprazole, the authors noted the existence of data for 29 cases, reported mostly in the form of case reports.⁷ Considering the limited literature on the topic, especially in the context of substance-associated psychosis, we present a case of aripiprazole-related hiccups and discuss the current understanding of the association.

Case Report

A 29-year-old man, with a history of seizure disorder and depression, was admitted to the inpatient unit with psychotic symptoms (delusion of persecution, delusion of reference, auditory and visual hallucinations) in the context of methamphetamine use. Hence, diagnoses of stimulant-related disorder, including amphetamines, methamphetamine, and methcathinone; substance dependence; and substance-induced psychotic disorder as per the International Classification of Diseases, Eleventh Revision were considered. There was no history of hiccups, and no hiccups were noted at admission.

On presentation, there was no physical abnormality, and his routine blood investigations (hemogram, serum electrolytes, renal function tests, liver function tests, fasting blood glucose levels, and lipid profile) were normal. At admission, he was on mirtazapine 15 mg/day, valproate 200 mg twice daily, and melatonin 5 mg/day.

Given the patient’s psychotic symptoms, he was started on aripiprazole 10 mg/day. However, on day 2 after 2 doses of aripiprazole, he developed hiccups, initially infrequent, but by the end of day 3, their frequency increased significantly to every 3–5 seconds, leading to significant sleep disturbance and inability to eat. A detailed review of neurological (abnormal sensation, dizziness, headache, or diplopia) and gastrointestinal symptoms (heartburn, dysphagia, regurgitation, or abdominal pain) provided no evidence of any other abnormality. The physical examination, including vital signs, pulmonary and cardiac auscultation, and abdominal and neurological examination, revealed no abnormality. A review of history for withdrawal symptoms due to the use of methamphetamine also provided no evidence of a similar experience in the past. Common management including breath-holding and pinching of the nose was ineffective, and administration of baclofen led to a reduction in the frequency of his hiccups but not complete cessation.

Given the absence of any other attributing cause, the possibility of aripiprazole-associated hiccups was considered, and the medication was discontinued. Within 24 hours of missing the doses of aripiprazole, the frequency of hiccups reduced significantly, and by the end of 48 hours since the last dose, his hiccups ceased completely. On day 5, he was started on asenapine 5 mg twice/day with a good antipsychotic response, and no further hiccups were reported. Within a few days, he again presented with substance-induced psychotic disorder twice, but was not observed to be experiencing hiccups while going through the withdrawal phase. He was detoxified, provided relapse prevention counselling, and referred to the community mental health team for further management.

Discussion

In our case, hiccups were clearly evident after the second dose of aripiprazole 10 mg/day, and the symptoms resolved within 48 hours of stopping aripiprazole. Given the absence of other etiological factors and the temporal correlation between aripiprazole use and the onset of hiccups, a final diagnosis of aripiprazole-induced hiccups was considered. The Naranjo Adverse Drug Reaction Probability Scale⁸ score for the association in our case was 7, suggesting a probable association. A review of literature on aripiprazole-associated hiccups suggests that they are mostly seen in adolescents and young males and across various psychiatric disorders, with doses ranging from 2.5 to 30 mg/day and the majority of cases emerging within 1–2 days of starting aripiprazole and resolving within 1–4 days of stopping the medication.⁷

In general, antipsychotics have been used for the management of hiccups, with chlorpromazine being the only approved antipsychotic medication for the indication.⁹ However, rarely, antipsychotics have also been reported to be associated with the development of hiccups. Among the various antipsychotics, most are with aripiprazole, and hiccups have been reported to be associated with both oral and long-acting formulations. Different mechanisms have been suggested for this rare side effect of aripiprazole. As aripiprazole is known to be a dopamine partial agonist, in addition to the antidopaminergic action, it is suggested that it could possibly increase dopaminergic stimulation at low doses, which may hyperexcite the phrenic nerve in the brain stem and trigger the hiccup reflex.^10,11 This low-dose sensitivity explains why hiccups occur more frequently even at initiation with low doses.^4,7 Additionally, it is also suggested to stimulate serotonin 1A receptors rather than simply antagonizing them,^12,13 which can enhance phrenic motor activity and induce hiccups.¹⁴

In conclusion, our case adds to the limited literature on aripiprazole-associated hiccups and suggests that when considering the use of aripiprazole, clinicians should always review the patient’s history of hiccups and prescribe aripiprazole cautiously when present. Additionally, when a patient taking aripiprazole reports hiccups, an association with the medication should be considered.

Article Information

Published Online: August 25, 2026. https://doi.org/10.4088/PCC.26cr04224
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(4):26cr04224
Submitted: March 5, 2026; accepted May 18, 2026.
To Cite: Ge T, Yadav S, Chen C, et al. Aripiprazole-induced persistent hiccups in an adult with drug-induced psychosis. Prim Care Companion CNS Disord 2026;28(4):26cr04224.
Author Affiliations: Mental Health Division, Northern Hospital, Melbourne, Australia (Ge, Yadav, Chen, Grover); Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandīgarh, India (Grover).
Corresponding Author: Sandeep Grover, MD, FRANZCP, Mental Health Division, Northern Hospital, Melbourne, Australia ([email protected]).
Financial Disclosure: None.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information has been de-identified to protect patient anonymity.