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Gabapentin for intractable hiccup

2004; Elsevier BV; Volume: 117; Issue: 4 Linguagem: Inglês

10.1016/j.amjmed.2004.03.019

1555-7162

José L. Hernández, Marcos Pajarón, Oscar García‐Regata, Virginia Jiménez Rodríguez, Jesús González‐Macías, Ciro Ramos‐Estebanez,

Pharmacological Effects of Natural Compounds

We report a patient with a history of Guillain-Barré syndrome and metastatic gastric neoplasm who presented with intractable hiccup that successfully responded to treatment with gabapentin plus baclofen. A 71-year-old man was hospitalized in December 2003 because of intractable hiccup and vomiting. Guillain-Barré syndrome was diagnosed in 1988 that caused bilateral lower limb, mild distal residual weakness and sensory loss. In May 2002, the patient had trouble swallowing liquids and food, and daylong hiccup started. A gastroscopy showed a gastric adenocarcinoma. Cancer infiltration of the anterior pillar of the diaphragm was noted at surgery. Chemotherapy and radiotherapy were started in July 2002. The hiccup persisted at a rate of 5 to 8 events per minute, with a total 3-hour hiccup-free interval. No specific therapy was initiated. In March 2003, he was referred to a neurologist due to aggravation of his leg weakness. Relapse of Guillain-Barré syndrome was suspected, but the patient refused immunoglobulin therapy. The hiccup pattern persisted. In November 2003, an abdominal computed tomographic (CT) scan revealed a lymphadenopathy over the left diaphragmatic pillar that was suggestive of metastatic origin. Hiccup bouts become continuous (10 to 15/min), usually leading to vomiting. He was unable to sleep and his nutritional condition was seriously affected. Oral deflazacort (30 mg/d) was started without improvement, and the patient was hospitalized. Chest radiograph showed bibasal infiltrates suggestive of aspiration pneumonia, and abdominal CT scan revealed diaphragmatic neoplastic infiltration. A barium series of the upper gastrointestinal tract showed no structural abnormalities or fistulas. Omeprazole (20 mg daily by mouth) and clorpromazine (25 mg three times daily) were initiated, but hiccup and vomiting persisted. Clorpromazine was withdrawn and baclofen (5 mg three times daily) was started. Baclofen was progressively increased to 15 mg three times daily, as the patient noted no improvement. Gabapentin (300 mg three times daily) was added. A day later, the hiccup ceased and the patient was able to eat. Sleep was restored. A week later the hiccup sporadically recurred, and gabapentin was increased to 400 mg daily. After 2 days, hiccup bouts resolved and the patient was transferred to the oncology department. Hiccup control remained unchanged 2 months later. Chronic or "intractable" hiccup remains a diagnostic challenge for the clinician. It relates to a broad spectrum of underlying disorders (1Pollack M.J. Intractable hiccups a serious sign of underlying systemic disease.J Clin Gastroenterol. 2003; 37: 272-273Crossref PubMed Scopus (14) Google Scholar). Although well-designed clinical studies are scarce, baclofen, a γ-aminobutyric acid (GABA) analogue leading to a perceptual blockage in synaptic transmission, is considered the cornerstone for the treatment of idiopathic intractable hiccup (2Ramirez F.C. Graham D.Y. Treatment of intractable hiccup with baclofen results of a double-blind randomized, controlled, cross-over study.Am J Gastroenterol. 1992; 87: 1789-1791PubMed Google Scholar). Gabapentin is structurally related to GABA. Nevertheless, it is not an inhibitor of GABA uptake or degradation, nor is it converted metabolically into GABA or a GABA agonist. Blood levels of gabapentin are quite predictable (about 3% circulates bound to plasma protein). It is not appreciably metabolized in humans and is eliminated by renal excretion as unchanged drug. The absence of liver metabolism is particularly useful in patients with cancer and metastatic spread. Dizziness, somnolence, and peripheral edema are the most frequent side effects (3Rose M.A. Kam P.C. Gabapentin pharmacology and its use in pain management.Anaesthesia. 2002; 57: 451-462Crossref PubMed Scopus (369) Google Scholar). Gabapentin has recently been suggested as a potential therapy for intractable hiccup. Seven cases have been reported (Table) (4Porzio 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: 605-607Google Scholar, 5Petroianu G. Hein G. Stegmeier-Petroianu A. et al.Gabapentin "add-on therapy" for idiopathic chronic hiccup (ICH).J Clin Gastroenterol. 2000; 30: 321-324Crossref PubMed Scopus (35) Google Scholar). The mechanism by which gabapentin decreases hiccup is not well understood. It may selectively diminish calcium influx by inhibiting voltage-operated calcium channels in a subset of excitatory and inhibitory presynaptic terminals, thereby attenuating synaptic transmission (6van Hooft J.A. Dougherty J.J. Endeman D. et al.Gabapentin inhibits presynaptic Ca(2+) influx and synaptic transmission in rat hippocampus and neocortex.Eur J Pharmacol. 2002; 449: 221-228Crossref PubMed Scopus (71) Google Scholar). Indeed, gabapentin probably increases the endogenous release of GABA, modulating excitability of the diaphragm and the other inspiratory muscles (4Porzio 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: 605-607Google Scholar, 5Petroianu G. Hein G. Stegmeier-Petroianu A. et al.Gabapentin "add-on therapy" for idiopathic chronic hiccup (ICH).J Clin Gastroenterol. 2000; 30: 321-324Crossref PubMed Scopus (35) Google Scholar). In this patient, the most probable cause for hiccup was the neoplastic infiltration of the diaphragm and thus gabapentin may have been useful for the former reason.TableCharacteristics of Patients with Chronic Hiccup Treated with GabapentinAge (ref.)SexRelated ConditionMedicationsDuration of Hiccup (months)Frequency (/min)Previous TherapyGabapentin Dosage (3 times/d)Treatment CombinationsHiccup Outcome62 (4Porzio 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: 605-607Google Scholar)MColon cancerNoneNRContinuousMetoclopramide300 mgNoReliefLiver metastasesDexamethasoneChlorpromazine43 (4Porzio 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: 605-607Google Scholar)MPancreas cancerNoneNRNRMetoclopramide300 mgNoRecurrenceHaloperidol400 mgResolution51 (4Porzio 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: 605-607Google Scholar)MSmall-cell lung cancerMorphineNRNRNone300 mgNoReliefBrain and liver metastases75 (5Petroianu G. Hein G. Stegmeier-Petroianu A. et al.Gabapentin "add-on therapy" for idiopathic chronic hiccup (ICH).J Clin Gastroenterol. 2000; 30: 321-324Crossref PubMed Scopus (35) Google Scholar)MCADNitrates9630–40Levomepromazine400 mgCOGResolutionCOPDVerapamilPromethazineDiabetes mellitusCaptoprilClorazepateDigoxinDomperidoneIpratropium bromideCisaprideFlunitrazepamBudesonideCarbamazepineInsulinLipoic acidBaclofenHipnotic therapyHerbal remedies58 (5Petroianu G. Hein G. Stegmeier-Petroianu A. et al.Gabapentin "add-on therapy" for idiopathic chronic hiccup (ICH).J Clin Gastroenterol. 2000; 30: 321-324Crossref PubMed Scopus (35) Google Scholar)MAlcoholismOmeprazole326–20Phrenicotomy400 mgCOGRecurrenceHiatal herniaCisaprideSemifundoplication400 mgCOBGReliefReflux esophagitisPethidineAcupunctureSeminomaNortryptilineHerbal remediesDoxepinTiaprideMistletoe extract55 (5Petroianu G. Hein G. Stegmeier-Petroianu A. et al.Gabapentin "add-on therapy" for idiopathic chronic hiccup (ICH).J Clin Gastroenterol. 2000; 30: 321-324Crossref PubMed Scopus (35) Google Scholar)MGastroesophageal refluxCisapride85Triflupromazine400 mgCOGRecurrenceAmytriptilineCisaprideCOBGReliefDuodenitisPantoprazoleNordazepamHerbal remedies74 (5Petroianu G. Hein G. Stegmeier-Petroianu A. et al.Gabapentin "add-on therapy" for idiopathic chronic hiccup (ICH).J Clin Gastroenterol. 2000; 30: 321-324Crossref PubMed Scopus (35) Google Scholar)MGastroesophageal refluxPhenprocoumon1220Carbamazepine400 mgCOGResolutionIsosorbide dinitrateTriflupromazineAxial hiatal herniaAcupunctureCADVerapamilPulmonary embolismDigoxinRecurrent deep venous thrombosisCarbamazepinTriflupromazine71 (Present case)MGastric cancerTriazolam2010–15Deflazacort300 mgOBGRecurrenceGuillain-Barré syndromeFolinic acidOmeprazole400 mgResolutionPhentanylChlorpromazineBaclofenC = cisapride (10 mg three times daily); CAD = coronary artery disease; COPD = chronic obstructive pulmonary disease; G = gabapentin; M = male; NR = not reported; O = omeprazole (20 mg/d); B = baclofen (15 mg three times daily). Open table in a new tab C = cisapride (10 mg three times daily); CAD = coronary artery disease; COPD = chronic obstructive pulmonary disease; G = gabapentin; M = male; NR = not reported; O = omeprazole (20 mg/d); B = baclofen (15 mg three times daily). In summary, gabapentin should be considered as an alternative therapy to control intractable hiccup. It could be particularly useful in patients with solid malignancies, either alone or as an "add-on therapy" with baclofen.