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MEDICAL JOURNALVol 116 No 1182 ISSN 1175 8716 Hiccup in patients with advanced cancer successfully treated
with gabapentin: report of three cases

Giampiero Porzio, Federica Aielli, Filomena Narducci, Giustino Varrassi, EnricoRicevuto, Corrado Ficorella and Paolo Marchetti Chronic hiccup is an infrequent but distressing symptom in patients with advancedcancer. A series of drugs (chlorpromazine, haloperidol, nifedipine, metoclopramide,baclofen) have been proposed to treat hiccup without definitive results. Some authorshave suggested a possible role of gabapentin in the treatment of idiopathic chronichiccup in patients not affected by neoplasms.1,2 We report three cases of hiccup inpatients with advanced cancer successfully treated with gabapentin observed at theSupportive Care and Rehabilitation Unit of the Medical Oncology Department,University of L’Aquila, Italy.
A 62-year-old man with a history of colon cancer metastasised to the liver wasadmitted for chronic hiccup, nausea and fatigue. He was previously treated by hisfamily physician with metoclopramide and dexamethasone without effect. Atadmission the patient was suffering and distressed due to continuous hiccup and sleepdeprivation. Chlorpromazine (25 mg iv bid) was started with relief of hiccup but withpostural hypotension and severe drowsiness. After two days hiccup recurred;chlopromazine was stopped and gabapentin (300 mg tid) was introduced. Weregistered a prompt relief of hiccup with only sporadic episodes successfully treatedwith empiric methods. Sleep was restored. No side effects related to gabapentin werenoted. After six days the patient developed jaundice and died by progression ofdisease. No recurrence of hiccup was observed.
A 43-year-old man affected by pancreatic cancer was referred for pain, nausea andchronic hiccup.
Hiccup and nausea were treated with metoclopramide (1 mg/kg) and haloperidol (5mg sc continous infusion) with good results. After one week hiccup recurredaccompanied by anxiety, nervousness and sleep deprivation.
Gabapentin (300 mg tid) was added to the treatment with a prompt resolution of thesymptom. Hiccup recurred after ten days with lower intensity; gabapentin wasincreased to 400 mg tid with remission of the symptom. After fourteen days thepatient died by progression of disease without recurrence of hiccup.
A 51-year-old man affected by small-cell lung cancer metastasised to the brain andliver was referred for pain, dyspnoea, anorexia and hiccup. Since the pain wasclassified as somatic and neuropathic, a therapy with oral morphine and gabapentin(300 mg tid) was started. We registered a prompt resolution of hiccup. Sporadic URL: http://www.nzma.org.nz/journal/116-1182/605/ episodes of hiccup were successfully treated with oral metoclopramide. After twentydays the patient died by progression of the disease.
Discussion
Chronic hiccup is defined as hiccup lasting 48 hours continuously or in recurringattacks and is a very distressing symptom for patients with advanced cancer.3 Theliterature is based largely on case reports and no definitive clinical evidence isavailable to define the standard treatment. To date, chlorpromazine, haloperidol,nifedipine, metoclopramide and baclofen are the drugs most commonly employed inclinical practice. In particular, baclofen seems to be the drug most commonlyemployed to treat hiccup, but with frequent side effects (sedation, insomnia, dizziness,weakness, ataxia, confusion).4,5 Moreover, it should be used with caution in elderlypatients.
Gabapentin is an anticonvulsant commonly administered to patients with advancedcancer for the treatment of neuropathic pain.6 It is not metabolised by the liver and not bound to plasma proteins. Thesecharacteristics make the drug particularly attractive for patients with advanced cancerwho often exhibit a low level of plasma proteins and/or hepatic failure due tometastatic spread.
The mechanism of action is probably related to the increase of endogenous GABArelease and, thus, to the modulation of the excitability of the diaphragm and the otherinspiratory muscles.1 Gabapentin is well tolerated and negative interactions with other drugs should not beexpected.
In our experience, gabapentin was effective either alone or in combination with otherdrugs to treat chronic hiccup; no side effects related to gabapentin were observed.
Trials with a larger number of patients are mandatory to establish the role ofgabapentin for treatment of hiccup in patients with advanced cancer.
Author information: Giampiero Porzio, Research Associate; Federica Aielli,
Registrar in Medical Oncology; Filomena Narducci, Registrar in Medical Oncology,
Supportive Care and Rehabilitation Unit, Medical Oncology Department; Giustino
Varrassi, Director, Anaesthesiology and Pain Therapy Unit; Enrico Ricevuto,
Research Associate; Corrado Ficorella, Associate Professor; Paolo Marchetti,
Director, Medical Oncology Department, University of L’Aquila, Italy
Correspondence: Giampiero Porzio, Dipartimento di Medicina Sperimentale,
Universita degli Studi – 67100 L’Aquila, Italy. Fax: +39 0862 368264; email:
porzio1@interfree.it
References:
1. Petroianu G, Hein G, Stegmeier-Petroianu A, et al. Gabapentin “add-on therapy” for idiopathic chronic hiccup (ICH). J Clin Gastroenterol 2000;30:321–4.
2. Moretti R, Torre P, Antonello RM et al. Treatment of chronic hiccups: new perspectives. Eur J 3. Launois S, Bizec JL, Whitelaw WA et al. Hiccup in adults: an overview. Eur Respir J URL: http://www.nzma.org.nz/journal/116-1182/605/ 4. Ramirez FC, Graham DY. Treatment of intractable hiccup with baclofen: results of a double- blind randomized, controlled, cross-over study. Am J Gastroenterol 1992;87:1789–91.
5. Walker P, Watanabe S, Bruera E. Baclofen, a treatment for chronic hiccup. J Pain Symptom 6. Mellegers MA, Furlan AD, Mailis A. Gabapentin for neuropathic pain: systematic review of controlled and uncontrolled literature. Clin J Pain 2001;17:284–95.
URL: http://www.nzma.org.nz/journal/116-1182/605/

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