Case Study Gabapentin for the Treatment of Persistent Hiccups
Background
Peter Campbell, Sharon Janak, Olga Hilas
OBJECTIVE: To report a case of persistent hiccups successfully treated with gabapentin in an elderly male. SETTING: An acute care unit for elders within a large teaching hospital. case summary: An 86-year-old male was admitted to the hospital for treatment of a urinary tract infection. In addition to his infection, the patient complained of bothersome hiccups with an onset several days prior to admission. He received metoclopramide for two days without improvement. Based on his medical history and a probable neurogenic etiology, gabapentin was recommended for his hiccups. Symptoms improved within several hours, with complete resolution after a dose titration to 200 mg twice daily on the second day of gabapentin treatment. The patient was ultimately discharged back to his long-term care facility, but was readmitted three days later for the treatment of pneumonia. His hiccups recurred and were treated unsuccessfully with metoclopramide in the emergency department. Gabapentin was reinitiated by the geriatric medicine team, and the patient’s hiccups resolved once again. CONCLUSION: Randomized, controlled trials evaluating the use of gabapentin in the treatment of hiccups associated with neurogenic etiologies are lacking; however, case reports suggest that this agent may be an effective treatment option. Key Words: Elderly, Gabapentin, Hiccups, Neurology, Older
adults, Stroke. Abbreviations: CPSP = Central poststroke pain, FDA = Food
and Drug Administration, GABA = Gamma-aminobutyric acid, GI = Gastrointestinal, IV = Intravenous, UTI = Urinary tract infection. Consult Pharm 2014;29:408-12.
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Gabapentin is a gamma-aminobutyric acid (GABA) analog approved by the Food and Drug Administration (FDA) as an adjunct for partial seizures in adult and pediatric patients (three years of age and older), and for the management of postherpetic neuralgia in adults. This agent has also been used in the treatment of various clinical conditions (e.g., neuropathic pain, diabetic neuropathy, restless leg syndrome). While the exact mechanism of gabapentin is unclear, neither the drug nor its metabolites bind to GABA receptors or influence the uptake of GABA.1 It has been hypothesized that gabapentin may inhibit or modulate voltage-gated calcium channels involved in action potentials and may also play a role in the resolution of hiccups.1,2 Hiccups are involuntary diaphragmatic contractions followed by early glottis closures that cause inspirations to terminate prematurely.3-6 The exact mechanism by which hiccups occurs is unknown, but may involve impulse generation through an afferent limb, a central mediator, and an efferent limb. The afferent limb is made up of the phrenic and vagus nerves as well as other nerves of the sympathetic chain. The central mediator is believed to be between the cervical spine and brainstem. The efferent limb consists of motor fibers of the phrenic nerve extending to the glottis, diaphragm, and inspiratory muscles.3,7-13 In some cases, patients may suffer from hiccups for a prolonged period of time leading to complications such as fatigue, sleep disturbances, dehydration, dysphagia, malnutrition, and aspiration pneumonia.4-6,14 Hiccups lasting for more than 48 hours are termed “persistent,” while episodes lasting one month or longer are classified as “intractable.”3-6 Possible causes of prolonged hiccups include gastrointestinal diseases (GI) (e.g., gastroesophageal reflux, inflammatory bowel), central nervous system disorders (e.g., stroke, brain injury), metabolic abnormalities (e.g., hypokalemia, hypocalcemia, uremia), and certain medications (e.g., anesthetics, barbiturates, benzodiazepines, opioids, steroids).5,7-10 The management of persistent or intractable hiccups often includes pharmacologic therapy. Currently, chlorpromazine is the only FDA-approved medication
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Gabapentin for the Treatment of Persistent Hiccups
for the treatment of hiccups, although other agents (e.g., haloperidol, metoclopramide, baclofen, phenytoin, valproic acid, carbamazepine) have also been found effective as a result of mediating the hiccup reflex.4,7-10,15-21 Gabapentin’s proposed mechanism of blocking neuronal calcium channels and promoting GABA release (resulting in decreased excitability of the diaphragm) may help to explain its role in the management of hiccups, particularly in patients with neurologic predispositions.5,7,17,22-25
Case Report An 86-year-old man presented to the emergency department with a past medical history significant for Alzheimer’s disease, chronic obstructive pulmonary disease, paroxysmal atrial fibrillation, hypertension, diastolic heart failure, hyperlipidemia, benign prostatic hyperplasia, recurrent pneumonia, epilepsy, and multiple strokes. His medications included aspirin, budesonide, divalproex, donepezil, hydrochlorothiazide, ipratropium, isosorbide dinitrate, rosuvastatin, and tamsulosin. The patient presented with altered mental status and fever and was admitted to the acute care for elders unit for the treatment of a urinary tract infection (UTI). He also reported a new onset of worsening hiccups with associated abdominal pain and decreased oral intake, which presented five to six days prior to admission. The patient was given one dose of metoclopramide 5 mg intravenously (IV), followed by 10 mg IV every eight hours for a total of two days without symptom improvement. On the third day, no metoclopramide was administered; instead, gabapentin 100 mg orally twice daily was initiated, and the patient’s hiccups improved within several hours of the first administered dose. He was titrated to a gabapentin dose of 200 mg orally twice daily on the following day, with complete resolution of hiccups occurring within the subsequent 24 hours. After appropriate treatment of his UTI and hiccups, the patient was discharged back to his long-term care facility. Three days after discharge, the patient was readmitted for altered mental status, fever, and cough. A diagnosis of health care-associated pneumonia was made, and the patient was initiated on appropriate antibiotic therapy. He also complained of worsening hiccups and was given two
doses of metoclopramide 10 mg IV while in the emergency department, with no symptom resolution. Upon readmission to the geriatric service and medication reconciliation perfomed by the clinical pharmacist, gabapentin 100 mg orally twice daily was reinitiated, with improvement of the hiccups within a few hours of the first dose. On the following day, gabapentin was titrated to 200 mg orally twice daily, leading to complete symptom resolution within 24 hours. After appropriate treatment of his health care-associated pneumonia, the patient was discharged on gabapentin 200 mg orally twice daily, with re-evaluation of hiccups recommended at the long-term care facility.
Discussion Gabapentin was recommended for our patient after a review of the literature and careful consideration of other frequently used medications for the resolution of hiccups. In particular, an antipsychotic agent was not selected for use in this patient given the increased risks of cardiac and dystonic adverse reactions, dysphagia, hospitalizations, and death in older patients and those with dementia.20,26-29 There was also less concern for potential drug interactions and side effects associated with the use of gabapentin over the other aforementioned medications frequently used to treat hiccups. Although gabapentin is known to cause somnolence and GI discomfort, these adverse effects were not observed, likely because of the relatively low doses administered to our patient. Gabapentin is eliminated by the kidneys and should be used cautiously in older patients and patients with renal insufficiency.1 Therefore, renal function was assessed and closely monitored for the duration of the patient’s hospital stay. The etiology of persistent or intractable hiccups is often unclear, but in this case it was suspected to be a complication of the patient’s stroke history. Our case report is consistent with the previously published reports reviewed below, which suggest that gabapentin may have a role in the treatment of persistent hiccups in patients with neurogenic causes.2,14,15,21,29,31 Recently, Carlisi et al. reported a case of hiccups after surgical resection of a brainstem arteriovenous malformation in a 21-year-old male.14 Postsurgery, the
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Case Study patient had experienced persistent hiccups that ultimately interfered with feeding and sleep in the neurorehabilitation unit. Chlorpromazine 25 mg orally three times daily was administered to the patient with no improvement in symptoms. Lorazepam 2 mg orally twice daily was added after six days, but provided no additional relief and was replaced with gabapentin 300 mg orally twice daily, which immediately began to improve the hiccups. Gabapentin was titrated to a dose of 400 mg three times daily for the complete resolution of hiccups and associated dysesthesia. Treatment with gabapentin was continued for 60 days, followed by dose reduction and discontinuation. The patient reported no adverse effects and remained asymptomatic at his 12-month follow-up. Schuchmann et al. described two cases of persistent hiccups of neurogenic origin successfully treated with gabapentin.21 One case involved a 60-year-old male whose hiccups began after a lateral medullary infarct. Hiccups persisted for nine days resulting in nausea and emesis, as well as poor fluid and nutritional intake. Baclofen 5 mg was initiated three times daily and was subsequently increased to 10 mg orally three times daily, with no improvement. Baclofen was discontinued, and chlorpromazine 25 mg orally three times daily was administered, providing some alleviation of the hiccups. However, the patient experienced worsening dizziness and orthostatic hypotension as a result of chlorpromazine treatment. Chlorpromazine was discontinued, and gabapentin 100 mg orally four times daily was initiated. The patient’s hiccups, along with the associated dizziness, nausea, and emesis, promptly resolved without recurrence. The second case involved a 72-year-old female who developed a hematoma on her cervical spinal cord as a result of a fall and excessive anticoagulation with warfarin. Upon her admission to a rehabilitation center for persistent right hemiparesis, the patient reported bothersome hiccups, which had been interfering with her ability to eat and drink for three days. She received chlorpromazine 25 mg orally three times daily with great improvement; however, dizziness and orthostatic hypotension interfering with her rehabilitation activities had resulted from treatment. Chlorpromazine was discontinued, and gabapentin
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100 mg four times daily was initiated with complete resolution of the hiccups. Gabapentin was then tapered and discontinued without any recurrence. Alonso-Navarro et al. reported a case of a 69-year-old female with intractable hiccups resulting after an amygdalectomy.15 The patient had been experiencing these hiccups intermittently for 50 years, which had been unsuccessfully treated with various pharmacologic agents (i.e., chlorpromazine, promethazine, valproate, and clonazepam). Gabapentin 400 mg orally once daily gradually improved the hiccups, with complete resolution after a dose titration to gabapentin 400 mg orally three times daily. Treatment was eventually discontinued, but the hiccups recurred. Gabapentin was reintroduced and once again titrated to 400 mg orally three times daily, which fully resolved her symptoms. Liang et al. described the treatment of two patients with persistent hiccups associated with lateral medullary infarctions.29 In the first case, a 69-year-old male who described his hiccups as his “most-distressing” issue, complained of problems sleeping, eating, and partaking in various activities. He was sequentially treated with metoclopramide 5 mg orally three times daily, followed by chlorpromazine 25 mg orally three times daily, and baclofen 5 mg orally three times daily, with no resolution of symptoms. Gabapentin 100 mg orally three times daily was then initiated and increased to 300 mg three times daily. Improvement of hiccups was noted within 24 hours of gabapentin treatment, with complete resolution reported within 72 hours. Gabapentin was discontinued after one week. No adverse effects had occurred during therapy with gabapentin, and no recurrences were documented at the 12-month follow-up. In the second case, a 67-year-old male experienced similar persistent hiccups and was treated with gabapentin 300 mg orally three times daily, with complete resolution of symptoms within two days. The dose was reduced to 300 mg orally once daily for an additional three days of therapy, then gabapentin was discontinued with no subsequent recurrence of hiccups. Three weeks later, he was diagnosed with central poststroke pain (CPSP) and was prescribed a nonsteroidal anti-inflammatory drug,
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Gabapentin for the Treatment of Persistent Hiccups
acetaminophen, and a tricyclic antidepressant, which were all ineffective in controlling his overall pain. He was once again administered gabapentin 300 mg orally three times daily, followed by a dose titration to 400 mg orally three times daily, which significantly improved his pain within two weeks of treatment. Gabapentin was eventually discontinued, but pain returned within a few days. The patient was placed back on gabapentin 400 mg orally three times daily, and pain decreased once again; therefore, gabapentin therapy was maintained for CPSP. Moretti et al. reported the use of gabapentin in the treatment of 15 neurology clinic patients (mean age, 69.1 years) with persistent hiccups associated with ischemic brainstem lesions.2 All patients reported problems with sleep, nutrition, and other activities as a result of the bothersome hiccups. Gabapentin 400 mg orally three times daily was initiated in each patient for three days, followed by three days of 400 mg orally once daily. By day 2 of treatment, hiccups had resolved in all patients, with no adverse effects reported. Only one patient experienced a recurrence of hiccups two years after initial treatment. Once again, gabapentin was administered in the same manner and hiccups disappeared with long-term resolution. Moretti et al. also reported successful treatment of intractable hiccups associated with cerebrovascular infarction with gabapentin in eight other patients (mean age 64.4 years).30 Patients received 400 mg orally three times daily, followed by 400 mg orally once daily for three additional days. All patients reported almost complete resolution of hiccups by the second day of treatment with gabapentin, and remained asymptomatic for the duration of a six-month follow-up period.
Conclusion Currently, randomized controlled trials evaluating the use of gabapentin in the treatment of prolonged hiccups are lacking. However, case reports suggest that gabapentin is an effective treatment option for persistent or intractable hiccups with a more favorable safety profile than other agents in patients with neurogenic etiologies.
Peter Campbell, PharmD, is a PGY-1 pharmacy practice resident, New York-Presbyterian Hospital, New York, New York. Sharon Janak, PharmD, is pharmacist, Burke Rehabilitation Center, White Plains, New York. Olga Hilas, PharmD, MPH, BCPS, CGP, FASCP, is associate professor, Clinical Pharmacy Practice, St. John’s University, College of Pharmacy & Health Sciences, Queens, New York. For correspondence: Olga Hilas, PharmD, Clinical Pharmacy Practice, St. John’s University, College of Pharmacy & Health Sciences, 8000 Utopia Parkway, St. Albert Hall, Queens, NY 11439; Phone: 718-990-1887; Fax: 718-990-1986; E-mail: [email protected]. Disclosure: No funding was received for the development of this manuscript. The authors have no potential conflicts of interest. © 2014 American Society of Consultant Pharmacists, Inc. All rights reserved. Doi:10.4140/TCP.n.2014.408.
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Case Study References 1. Neurontin (gabapentin) prescribing information. New York, NY: ParkeDavis; 2012. 2. Moretti R, Torre P, Antonello RM et al. Gabapentin as a drug therapy of intractable hiccup because of vascular lesion: a three-year follow up. Neurologist 2004;10:102-6. 3. Smith HS. Hiccups: In Palliative Medicine. New York, NY: Saunders; 2009:894-8. 4. Smith HS, Busracamwongs A. Management of hiccups in the palliative care population. Am J Hosp Palliat Care 2003;20:149-54. 5. Woelk CJ. Managing hiccups. Can Fam Phys 2011;57:672-5. 6. Kolodzik PW, Eilers MA. Hiccups (singultus): review and approach to management. Ann Emerg Med 1991;20:565. 7. Oshima T, Sakamoto M, Tatsuta H et al. GABAergic inhibition of hiccup-like reflex induced by electrical stimulation in medulla of cats. Neurosci Res 1998;30:287-93. 8. Becker DE. Nausea, vomiting, and hiccups: a review of mechanisms and treatment. Anesth Prog 2010;57:150-6. 9. Wang PH, Fuh JL. Hiccups-functional or pathological? J Chin Med Assoc 2011;74:197. 10. Page RL, Luna M, Brieke A et al. Low-dose gabapentin for intractable hiccups in a heart transplant recipient. Prog Transplant 2011;21:340-3. 11. Lee MH, Pritchard JM, Weiner WJ. Clinical reasoning: a 44-year-old man with a 3-month history of hiccups. Neurology 2011;77:e145-8. 12. Loft LM, Ward RF. Hiccups. A case presentation and etiologic review. Arch Otolaryngol Head Neck Surg 1992;118:1115-9. 13. Ong AM, Tan CS, Foo MW et al. Gabapentin for intractable hiccups in a patient undergoing peritoneal dialysis. Perit Dial Int 2008;28:667-8. 14. Carlisi E, Bossi D, Zaliani A et al. Persistent hiccup after surgical resection of a brainstem arteriovenous malformation: a case successfully treated with gabapentin during rehabilitation. Eur J Phys Rehabil Med 2012;48:289-91. 15. Alonso-Navarro H, Rubio L, Jiménez-Jiménez FJ. Refractory hiccup: successful treatment with gabapentin. Clin Neuropharmacol 2007;30: 186-7. 16. Chlorpromazine prescribing information. Minneapolis, MN: UpsherSmith Laboratories, Inc.; June 2011.
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17. Marinella MA. Diagnosis and management of hiccups in the patient with advanced cancer. J Support Oncol 2009;7:122-7, 130. 18. Chang FY, Lu CL. Hiccup: mystery, nature and treatment. J Neurogastroenterol Motil 2012;18:123-30. 19. Calsina-Berna A, García-Gómez G, González-Barboteo J et al. Treatment of chronic hiccups in cancer patients: a systematic review. J Palliat Med 2012;15:1142-50. 20. Porzio G, Aielli F, Narducci F et al. Hiccup in patients with advanced cancer successfully treated with gabapentin: report of three cases. N Z Med J 2003;116:U605. 21. Schuchmann JA, Browne BA. Persistent hiccups during rehabilitation hospitalization: three case reports and review of the literature. Am J Phys Med Rehabil 2007;86:1013-8. 22. Kumar A, Dromerick AW. Intractable hiccups during stroke rehabilitation. Arch Phys Med Rehabil 1998;79:697-9. 23. Ferdinand P, Oke A. Intractable hiccups post stroke: case report and review of the literature. J Neurol Neurophysiol 2012;3:140. 24. Launois S, Bizec JL, Whitelaw WA et al. Hiccup in adults: an overview. Eur Respir J 1993;6:563-75. 25. van der Worp HB, Raaijmakers TW, Kappelle LJ. Early complications of ischemic stroke. Current Treatment Options in Neurology 2008;10:440-9. 26. Wu CS, Wang SC, Gau SSF et al. Association of stroke with receptorbinding profiles of antipsychotics. Biol Psychiatry 2013;73:414-21. 27. Chouinard J. Dysphagia in Alzheimer’s disease. J Nutr Health Aging 2000;4:214-7. 28. Rudolph JL, Gardner KF, Gramigna GD et al. Antipsychotics and oropharyngeal dysphagia in hospitalized older patients. J Clin Psychopharmacol 2008;28:532-5. 29. Liang CY, Tsai KW, Hsu MC. Gabapentin therapy for persistent hiccups and central post-stroke pain in lateral medullary infarction – two case reports and literature review. Tzu Chi Med J 2005;17:365-8. 30. Moretti R, Torre P, Antonello RM et al. Treatment of chronic hiccups: new perspectives. Eur J Neurol 1999;6:617-20.
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Background
Peter Campbell, Sharon Janak, Olga Hilas
OBJECTIVE: To report a case of persistent hiccups successfully treated with gabapentin in an elderly male. SETTING: An acute care unit for elders within a large teaching hospital. case summary: An 86-year-old male was admitted to the hospital for treatment of a urinary tract infection. In addition to his infection, the patient complained of bothersome hiccups with an onset several days prior to admission. He received metoclopramide for two days without improvement. Based on his medical history and a probable neurogenic etiology, gabapentin was recommended for his hiccups. Symptoms improved within several hours, with complete resolution after a dose titration to 200 mg twice daily on the second day of gabapentin treatment. The patient was ultimately discharged back to his long-term care facility, but was readmitted three days later for the treatment of pneumonia. His hiccups recurred and were treated unsuccessfully with metoclopramide in the emergency department. Gabapentin was reinitiated by the geriatric medicine team, and the patient’s hiccups resolved once again. CONCLUSION: Randomized, controlled trials evaluating the use of gabapentin in the treatment of hiccups associated with neurogenic etiologies are lacking; however, case reports suggest that this agent may be an effective treatment option. Key Words: Elderly, Gabapentin, Hiccups, Neurology, Older
adults, Stroke. Abbreviations: CPSP = Central poststroke pain, FDA = Food
and Drug Administration, GABA = Gamma-aminobutyric acid, GI = Gastrointestinal, IV = Intravenous, UTI = Urinary tract infection. Consult Pharm 2014;29:408-12.
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Gabapentin is a gamma-aminobutyric acid (GABA) analog approved by the Food and Drug Administration (FDA) as an adjunct for partial seizures in adult and pediatric patients (three years of age and older), and for the management of postherpetic neuralgia in adults. This agent has also been used in the treatment of various clinical conditions (e.g., neuropathic pain, diabetic neuropathy, restless leg syndrome). While the exact mechanism of gabapentin is unclear, neither the drug nor its metabolites bind to GABA receptors or influence the uptake of GABA.1 It has been hypothesized that gabapentin may inhibit or modulate voltage-gated calcium channels involved in action potentials and may also play a role in the resolution of hiccups.1,2 Hiccups are involuntary diaphragmatic contractions followed by early glottis closures that cause inspirations to terminate prematurely.3-6 The exact mechanism by which hiccups occurs is unknown, but may involve impulse generation through an afferent limb, a central mediator, and an efferent limb. The afferent limb is made up of the phrenic and vagus nerves as well as other nerves of the sympathetic chain. The central mediator is believed to be between the cervical spine and brainstem. The efferent limb consists of motor fibers of the phrenic nerve extending to the glottis, diaphragm, and inspiratory muscles.3,7-13 In some cases, patients may suffer from hiccups for a prolonged period of time leading to complications such as fatigue, sleep disturbances, dehydration, dysphagia, malnutrition, and aspiration pneumonia.4-6,14 Hiccups lasting for more than 48 hours are termed “persistent,” while episodes lasting one month or longer are classified as “intractable.”3-6 Possible causes of prolonged hiccups include gastrointestinal diseases (GI) (e.g., gastroesophageal reflux, inflammatory bowel), central nervous system disorders (e.g., stroke, brain injury), metabolic abnormalities (e.g., hypokalemia, hypocalcemia, uremia), and certain medications (e.g., anesthetics, barbiturates, benzodiazepines, opioids, steroids).5,7-10 The management of persistent or intractable hiccups often includes pharmacologic therapy. Currently, chlorpromazine is the only FDA-approved medication
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Gabapentin for the Treatment of Persistent Hiccups
for the treatment of hiccups, although other agents (e.g., haloperidol, metoclopramide, baclofen, phenytoin, valproic acid, carbamazepine) have also been found effective as a result of mediating the hiccup reflex.4,7-10,15-21 Gabapentin’s proposed mechanism of blocking neuronal calcium channels and promoting GABA release (resulting in decreased excitability of the diaphragm) may help to explain its role in the management of hiccups, particularly in patients with neurologic predispositions.5,7,17,22-25
Case Report An 86-year-old man presented to the emergency department with a past medical history significant for Alzheimer’s disease, chronic obstructive pulmonary disease, paroxysmal atrial fibrillation, hypertension, diastolic heart failure, hyperlipidemia, benign prostatic hyperplasia, recurrent pneumonia, epilepsy, and multiple strokes. His medications included aspirin, budesonide, divalproex, donepezil, hydrochlorothiazide, ipratropium, isosorbide dinitrate, rosuvastatin, and tamsulosin. The patient presented with altered mental status and fever and was admitted to the acute care for elders unit for the treatment of a urinary tract infection (UTI). He also reported a new onset of worsening hiccups with associated abdominal pain and decreased oral intake, which presented five to six days prior to admission. The patient was given one dose of metoclopramide 5 mg intravenously (IV), followed by 10 mg IV every eight hours for a total of two days without symptom improvement. On the third day, no metoclopramide was administered; instead, gabapentin 100 mg orally twice daily was initiated, and the patient’s hiccups improved within several hours of the first administered dose. He was titrated to a gabapentin dose of 200 mg orally twice daily on the following day, with complete resolution of hiccups occurring within the subsequent 24 hours. After appropriate treatment of his UTI and hiccups, the patient was discharged back to his long-term care facility. Three days after discharge, the patient was readmitted for altered mental status, fever, and cough. A diagnosis of health care-associated pneumonia was made, and the patient was initiated on appropriate antibiotic therapy. He also complained of worsening hiccups and was given two
doses of metoclopramide 10 mg IV while in the emergency department, with no symptom resolution. Upon readmission to the geriatric service and medication reconciliation perfomed by the clinical pharmacist, gabapentin 100 mg orally twice daily was reinitiated, with improvement of the hiccups within a few hours of the first dose. On the following day, gabapentin was titrated to 200 mg orally twice daily, leading to complete symptom resolution within 24 hours. After appropriate treatment of his health care-associated pneumonia, the patient was discharged on gabapentin 200 mg orally twice daily, with re-evaluation of hiccups recommended at the long-term care facility.
Discussion Gabapentin was recommended for our patient after a review of the literature and careful consideration of other frequently used medications for the resolution of hiccups. In particular, an antipsychotic agent was not selected for use in this patient given the increased risks of cardiac and dystonic adverse reactions, dysphagia, hospitalizations, and death in older patients and those with dementia.20,26-29 There was also less concern for potential drug interactions and side effects associated with the use of gabapentin over the other aforementioned medications frequently used to treat hiccups. Although gabapentin is known to cause somnolence and GI discomfort, these adverse effects were not observed, likely because of the relatively low doses administered to our patient. Gabapentin is eliminated by the kidneys and should be used cautiously in older patients and patients with renal insufficiency.1 Therefore, renal function was assessed and closely monitored for the duration of the patient’s hospital stay. The etiology of persistent or intractable hiccups is often unclear, but in this case it was suspected to be a complication of the patient’s stroke history. Our case report is consistent with the previously published reports reviewed below, which suggest that gabapentin may have a role in the treatment of persistent hiccups in patients with neurogenic causes.2,14,15,21,29,31 Recently, Carlisi et al. reported a case of hiccups after surgical resection of a brainstem arteriovenous malformation in a 21-year-old male.14 Postsurgery, the
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Case Study patient had experienced persistent hiccups that ultimately interfered with feeding and sleep in the neurorehabilitation unit. Chlorpromazine 25 mg orally three times daily was administered to the patient with no improvement in symptoms. Lorazepam 2 mg orally twice daily was added after six days, but provided no additional relief and was replaced with gabapentin 300 mg orally twice daily, which immediately began to improve the hiccups. Gabapentin was titrated to a dose of 400 mg three times daily for the complete resolution of hiccups and associated dysesthesia. Treatment with gabapentin was continued for 60 days, followed by dose reduction and discontinuation. The patient reported no adverse effects and remained asymptomatic at his 12-month follow-up. Schuchmann et al. described two cases of persistent hiccups of neurogenic origin successfully treated with gabapentin.21 One case involved a 60-year-old male whose hiccups began after a lateral medullary infarct. Hiccups persisted for nine days resulting in nausea and emesis, as well as poor fluid and nutritional intake. Baclofen 5 mg was initiated three times daily and was subsequently increased to 10 mg orally three times daily, with no improvement. Baclofen was discontinued, and chlorpromazine 25 mg orally three times daily was administered, providing some alleviation of the hiccups. However, the patient experienced worsening dizziness and orthostatic hypotension as a result of chlorpromazine treatment. Chlorpromazine was discontinued, and gabapentin 100 mg orally four times daily was initiated. The patient’s hiccups, along with the associated dizziness, nausea, and emesis, promptly resolved without recurrence. The second case involved a 72-year-old female who developed a hematoma on her cervical spinal cord as a result of a fall and excessive anticoagulation with warfarin. Upon her admission to a rehabilitation center for persistent right hemiparesis, the patient reported bothersome hiccups, which had been interfering with her ability to eat and drink for three days. She received chlorpromazine 25 mg orally three times daily with great improvement; however, dizziness and orthostatic hypotension interfering with her rehabilitation activities had resulted from treatment. Chlorpromazine was discontinued, and gabapentin
410
100 mg four times daily was initiated with complete resolution of the hiccups. Gabapentin was then tapered and discontinued without any recurrence. Alonso-Navarro et al. reported a case of a 69-year-old female with intractable hiccups resulting after an amygdalectomy.15 The patient had been experiencing these hiccups intermittently for 50 years, which had been unsuccessfully treated with various pharmacologic agents (i.e., chlorpromazine, promethazine, valproate, and clonazepam). Gabapentin 400 mg orally once daily gradually improved the hiccups, with complete resolution after a dose titration to gabapentin 400 mg orally three times daily. Treatment was eventually discontinued, but the hiccups recurred. Gabapentin was reintroduced and once again titrated to 400 mg orally three times daily, which fully resolved her symptoms. Liang et al. described the treatment of two patients with persistent hiccups associated with lateral medullary infarctions.29 In the first case, a 69-year-old male who described his hiccups as his “most-distressing” issue, complained of problems sleeping, eating, and partaking in various activities. He was sequentially treated with metoclopramide 5 mg orally three times daily, followed by chlorpromazine 25 mg orally three times daily, and baclofen 5 mg orally three times daily, with no resolution of symptoms. Gabapentin 100 mg orally three times daily was then initiated and increased to 300 mg three times daily. Improvement of hiccups was noted within 24 hours of gabapentin treatment, with complete resolution reported within 72 hours. Gabapentin was discontinued after one week. No adverse effects had occurred during therapy with gabapentin, and no recurrences were documented at the 12-month follow-up. In the second case, a 67-year-old male experienced similar persistent hiccups and was treated with gabapentin 300 mg orally three times daily, with complete resolution of symptoms within two days. The dose was reduced to 300 mg orally once daily for an additional three days of therapy, then gabapentin was discontinued with no subsequent recurrence of hiccups. Three weeks later, he was diagnosed with central poststroke pain (CPSP) and was prescribed a nonsteroidal anti-inflammatory drug,
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Gabapentin for the Treatment of Persistent Hiccups
acetaminophen, and a tricyclic antidepressant, which were all ineffective in controlling his overall pain. He was once again administered gabapentin 300 mg orally three times daily, followed by a dose titration to 400 mg orally three times daily, which significantly improved his pain within two weeks of treatment. Gabapentin was eventually discontinued, but pain returned within a few days. The patient was placed back on gabapentin 400 mg orally three times daily, and pain decreased once again; therefore, gabapentin therapy was maintained for CPSP. Moretti et al. reported the use of gabapentin in the treatment of 15 neurology clinic patients (mean age, 69.1 years) with persistent hiccups associated with ischemic brainstem lesions.2 All patients reported problems with sleep, nutrition, and other activities as a result of the bothersome hiccups. Gabapentin 400 mg orally three times daily was initiated in each patient for three days, followed by three days of 400 mg orally once daily. By day 2 of treatment, hiccups had resolved in all patients, with no adverse effects reported. Only one patient experienced a recurrence of hiccups two years after initial treatment. Once again, gabapentin was administered in the same manner and hiccups disappeared with long-term resolution. Moretti et al. also reported successful treatment of intractable hiccups associated with cerebrovascular infarction with gabapentin in eight other patients (mean age 64.4 years).30 Patients received 400 mg orally three times daily, followed by 400 mg orally once daily for three additional days. All patients reported almost complete resolution of hiccups by the second day of treatment with gabapentin, and remained asymptomatic for the duration of a six-month follow-up period.
Conclusion Currently, randomized controlled trials evaluating the use of gabapentin in the treatment of prolonged hiccups are lacking. However, case reports suggest that gabapentin is an effective treatment option for persistent or intractable hiccups with a more favorable safety profile than other agents in patients with neurogenic etiologies.
Peter Campbell, PharmD, is a PGY-1 pharmacy practice resident, New York-Presbyterian Hospital, New York, New York. Sharon Janak, PharmD, is pharmacist, Burke Rehabilitation Center, White Plains, New York. Olga Hilas, PharmD, MPH, BCPS, CGP, FASCP, is associate professor, Clinical Pharmacy Practice, St. John’s University, College of Pharmacy & Health Sciences, Queens, New York. For correspondence: Olga Hilas, PharmD, Clinical Pharmacy Practice, St. John’s University, College of Pharmacy & Health Sciences, 8000 Utopia Parkway, St. Albert Hall, Queens, NY 11439; Phone: 718-990-1887; Fax: 718-990-1986; E-mail: [email protected]. Disclosure: No funding was received for the development of this manuscript. The authors have no potential conflicts of interest. © 2014 American Society of Consultant Pharmacists, Inc. All rights reserved. Doi:10.4140/TCP.n.2014.408.
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