What Is the Latest on Treatment for Hiccups?

Jenny A. Van Amburgh, PharmD, BCACP, CDE

Disclosures

May 14, 2015

Question

What is the latest on treatment for hiccups?

Response from Jenny A. Van Amburgh, PharmD, BCACP, CDE
Assistant Dean of Academic Affairs; Clinical Professor, School of Pharmacy, Northeastern University; Director, Clinical Pharmacy Services & Residency Program, Harbor Health Services, Inc., Boston, Massachusetts

Affecting nearly everyone at least once in their life, a hiccup, or singultus, is a spontaneous, spasmodic contraction of the diaphragm and intercostal muscles, which is immediately followed by closure of the glottis. Air meeting the closed glottis produces the classic "hic" sound. Classification and determination of treatment is based on the duration and cause of hiccups. A bout of hiccups can last minutes to hours, while persistent hiccups last longer than 48 hours and intractable hiccups last longer than 1 month.[1] Although hiccups are generally benign, prolonged hiccups may lead to complications, including exhaustion, malnutrition, dehydration, or even death in extreme cases.[2]

Hiccups are usually self-limiting and resolve spontaneously with or without simple physical maneuvers, but pharmacologic treatment should be considered for hiccups lasting longer than 24 hours.

Common physical measures, or "folk remedies," include raising carbon dioxide pressure by holding one's breath and stimulation of the pharynx by sipping iced water, gargling, or swallowing granulated sugar. Although these remedies may provide relief, there is no scientific evidence to support their clinical efficacy on cessation of hiccups.[2,3]

Several pharmacologic treatments have demonstrated anecdotal efficacy in the treatment of hiccups, but only one drug—the antipsychotic agent chlorpromazine—has been approved by the US Food and Drug Administration (FDA).[2] Chlorpromazine may be used orally at 25-50 mg three to four times daily for intractable hiccups. Parenteral therapy can be considered if symptoms persist for 2-3 days.[4] Other medications that have limited evidence of efficacy for hiccups include but are not limited to muscle relaxants (eg, baclofen), anticonvulsants (eg, gabapentin, pregabalin, carbamazepine, valproic acid, phenytoin), antipsychotics (eg, olanzapine, haloperidol, risperidone), and various other drugs (eg, metoclopramide, carvedilol, amantadine).[2,3,5,6,7,8,9]

This article will review literature supporting the use of baclofen, gabapentin, or metoclopramide, three commonly used off-label medications, for the treatment of hiccups.

Baclofen is commonly used as a second-line therapy to chlorpromazine. Guelaud and colleagues[5] conducted a study following 37 patients with chronic hiccups treated with baclofen (5-25 mg three times daily). Baclofen treatment resulted in cessation of hiccups in 18 patients (49%) and marked improvement in hiccups in 10 patients (27%).

Gabapentin is thought to curb the excitatory activity of the diaphragm via blocking voltage-gated calcium channels, reducing the release of glutamate and substance P.[2] Thompson and Brooks[6] conducted a MEDLINE search producing three case series (66 patients total with improvement/cessation in 64 patients) and 17 case reports supporting the successful use of gabapentin for hiccups. The recommended dosing of gabapentin for persistent or intractable hiccups is 100 mg three to four times daily, titrated until improvement up to a maximum total daily dose of 1200 mg.[6]

Metoclopramide, a dopamine antagonist, has shown potential for hiccup cessation and decreased frequency via CNS depression. Wang and Wang[7] conducted a double-blinded, randomized, placebo-controlled study to investigate the use of metoclopramide in intractable hiccups. A dose of metoclopramide 10 mg three times daily resulted in 11 out of 17 patients (65%) with marked improvement in hiccups compared with 4 out of 17 patients (24%) on placebo.

Although chlorpromazine is generally considered first-line therapy for the treatment of hiccups, drug therapy choice can be guided on the basis of concomitant disease states or intolerability to chlorpromazine due to postural hypotension, excessive drowsiness, or dystonic reactions. Baclofen might be an option for patients who do not tolerate chlorpromazine. Patients with hiccups and a seizure disorder or neuropathic pain may benefit from treatment with gabapentin, while metoclopramide can be helpful for patients suffering from hiccups and gastroesophageal reflux disease.[6]

Above all, identifying the underlying cause of hiccups should be attempted first.

The author wishes to acknowledge the assistance of, Lisa Cillessen, PharmD, RPh; Amy Thein, PharmD, RPh; and Josephine Aranda, PharmD, RPh, PGY1 Residents at Northeastern University School of Pharmacy, in collaboration with Federally Qualified Health Centers and the Program of All-Inclusive Care for the Elderly, Boston, Massachusetts.

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