CASE REPORT

Hiccups Associated With Switching From Olanzapine to Aripiprazole in a Patient With Paranoid Schizophrenia Hikaru Hori, MD, PHD and Jun Nakamura, MD, PHD

Abstract: This article reports the case of a 29-year-old schizophrenic woman without somatic illness in whom switching from olanzapine to aripiprazole induced hiccups. Antipsychotics are thought to be effective in the treatment of hiccups; however, they have rarely been reported to induce hiccups. Within 24 hours of taking aripiprazole, the patient began having hiccups continuously. One week after the hiccups ceased, the patient resumed taking aripiprazole, and the hiccups began again. Although rare, this case study suggests that aripiprazole induces hiccups. Key Words: antipsychotics, aripiprazole, hiccups, schizophrenia (Clin Neuropharm 2014;37: 88–89)

H

iccups are the product of simultaneous involuntary spasmodic contractions of the diaphragm and glottic closure, resulting in the failure of air to enter the trachea.1 Antipsychotics are thought to be effective in the treatment of hiccups; however, they have rarely been reported to induce hiccups. Multiple causes have been attributed to the etiology of hiccups, including gastric distension or gastroesophageal reflux, drugs, lesions or infections of the central nervous system, and irritation of the phrenic or vagus nerves. We report a case of persistent hiccups after the administration of aripiprazole in a patient with paranoid schizophrenia. Aripiprazole, which is a partial agonist of dopamine D2 receptors and serotonin 1A receptors, may play a crucial role in the pathophysiology of hiccups.

CASE REPORT A 29-year-old female patient developed auditory hallucinations, delusions of reference and persecution, thought broadcasting, wandering behavior, amotivation, social withdrawal, decreased sleep and appetite, as well as impaired social functions, and she was admitted to the psychiatric ward at our hospital. Paranoid schizophrenia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, and treatment with 5-mg/d olanzapine was initiated. Five years later, she developed continuous dry mouth and increased body weight. She was tapered off olanzapine, and treatment with 12-mg/d aripiprazole was initiated. Within 24 hours

Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan. Address correspondence and reprint requests to Hikaru Hori, MD, PhD, Department of Psychiatry, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 8078555, Japan; E-mail: [email protected] Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/WNF.0000000000000032

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of taking aripiprazole, the patient began having hiccups continuously, for which she consulted a general medical practitioner. After a preliminary examination, she was advised to stop the aripiprazole. The patient reported no history of gastrointestinal disease, polydipsia, or substance abuse. Results of a neurologic examination were grossly normal. The blood, biochemistry, and thyroid function test results were unremarkable. The hiccups ceased approximately 56 hours after the last dose of aripiprazole. However, the patient desired to resume taking aripiprazole. One week after the hiccups stopped, she resumed taking aripiprazole, and the hiccups started again. She immediately stopped the aripiprazole and started 6-mg/d paliperidone. The hiccups did not recur during a maintenance treatment of 6-mg/d paliperidone for 6 months.

DISCUSSION Aripiprazole is a novel antipsychotic agent with a mechanism of action that differs from those of other typical and atypical agents. Functionally, aripiprazole is a partial agonist of the D2 and 5-HT1A receptors and an antagonist of the 5-HT2A receptor. The central mechanism of action of aripiprazole is believed to be the stabilization of dopamine and serotonin through the D2, 5-HT1A, and 5-HT2A receptors.2 Aripiprazole has a benign adverse-effect profile with little extrapyramidal adverse effects, minimal to no weight gain, and a favorable metabolic profile. Antipsychotics are thought to be effective in the treatment of hiccups; however, they have rarely been reported to induce hiccups. Curiously, hiccups have also been reported to result from antidopaminergic agents and levodopa treatment for Parkinson disease.3,4 The role of serotonin in hiccups is suggested by reports of the successful treatment of hiccups by sertraline and olanzapine and, interestingly, the induction of hiccups with clozapine.1,5,6 Regardless of the neurotransmitter mechanisms involved, hiccups can arise from idiopathic, psychogenic, and organic causes. The use of therapeutic drugs represents an important cause of hiccups. There have been only 2 reported cases of aripiprazole-induced hiccups, but both cases exhibited an organic problem.7,8 In this case, there was no identifiable organic problem. Because the hiccups developed shortly after starting aripiprazole in the absence of any clinical guidelines, it was a prudent, clinical practice to replace it with another antipsychotic agent, such as olanzapine or quetiapine. Further studies are needed to understand the role of neurotransmitters in the hiccup reflex and how different medications influence it.

REFERENCES 1. Alderfer BS, Arciniegas DB. Treatment of intractable hiccups with olanzapine following recent severe traumatic brain injury. J Neuropsychiatry Clin Neurosci 2006;18(4):551–552.

Clinical Neuropharmacology • Volume 37, Number 3, May/June 2014

Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Clinical Neuropharmacology • Volume 37, Number 3, May/June 2014

Hiccup From Olanzapine to Aripiprazole Switch

2. Naber D, Lambert M. Aripiprazole: a new atypical antipsychotic with a different pharmacological mechanism. Prog Neuropsychopharmacol Biol Psychiatry 2004;28(8):1213–1219.

6. Solla P, Congia S, Secchi L. Clozapine-induced persistent hiccup in a patient with Alzheimer’s disease. Clin Neurol Neurosurg 2006;108(6):614–618.

3. Miyaoka H, Kamijima K. Perphenazine-induced hiccups. Pharmacopsychiatry 1999;32(2):81.

7. Ray P, UI-Haq M, Nizamie SH. Aripiprazole-induced hiccup: a case report. Gen Hosp Psychiatry 2009;31(4):382–384.

4. Yardimci N, Benli S, Zileli T. A diagnostic challenge of Parkinson’s disease: intractable hiccups. Parkinsonism Relat Disord 2008;14(5):446–447.

8. Yeh YW. Persistent hiccups associated with switching from risperidone to aripiprazole in a schizophrenic patient with cerebral palsy. Clin Neuropharmacol 2011;34(4):135–136.

5. Vaidya V. Sertraline in the treatment of hiccups. Psychosomatics 2000;41 (4):353–355.

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Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

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Hiccups associated with switching from olanzapine to aripiprazole in a patient with paranoid schizophrenia.

This article reports the case of a 29-year-old schizophrenic woman without somatic illness in whom switching from olanzapine to aripiprazole induced h...
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