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What’s up with hiccups?

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September 5, 2017

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Mike Forbes
September 10, 2017

Drug Therapy of Hiccups

Full update March 2017
Hiccups, the involuntary contraction of the diaphragm, are common.1 Hiccups are caused by anything that stimulates the hiccup reflex arc. Acute hiccup attacks last less than 48 hours, while persistent hiccups last longer. Intractable hiccups are defined as an attack lasting more than one month.1,2 Although the incidence and prevalence are not known, one retrospective chart review found that of 100,000 consecutive patient visits to a hospital, 55 were for hiccups.3 Persistent hiccups may be a sign of an underlying problem. Before initiating medications to treat hiccups, correctable causes for hiccups should be investigated. Examples of underlying causes of hiccups include CNS abnormalities (e.g., meningitis, intracranial tumors, etc), gastrointestinal issues (e.g., peptic ulcer, gastroesophageal reflux disease, abdominal abscess, etc), thoracic diseases (e.g., pneumonia, asthma, etc), abnormalities of the ears-nose-throat (e.g., rhinitis, otitis media, etc), toxic exposures or metabolic derangements (e.g., alcohol, electrolyte abnormalities, etc), psychogenic causes (e.g., stress, fear, excitement, etc), post-surgical causes (e.g., anesthetic agents, pharyngeal intubation, etc), and medications (e.g., corticosteroids, opioids, benzodiazepines, etc).1,2,4 Pharmacological therapy should only be used if persistent hiccups are causing distress. Although home remedies such as breath holding, swallowing a spoonful of sugar, or drinking pickle juice are sometimes tried, the evidence to support these methods is scant. The table below summarizes drugs which have been used in the treatment of hiccups. Most of the treatments can be used for seven to ten days but can be discontinued one or two days after hiccups cease.4 If hiccups continue despite treatment, it is reasonable to consider a different medication.4 Of note, two different recent systematic reviews of the literature found no high quality data on which to base treatment recommendations.1,5

Abbreviations: GERD=gastroesophageal reflux disease; IM=intramuscular; IV=intravenous; PO=by mouth

*Most of the drugs below are used off-label for the treatment of hiccups. Dosing regimens will vary depending on the source*

Drug

Example Regimen(s)1,2,4

Comments
Antidopaminergic agents

Chlorpromazine

25 mg to 50 mg PO three to four times a day4,13

If symptoms persist after two to three days: 25 mg to 50 mg IM x113

If IM dose fails, try 25 mg to 50 mg IV administered as a slow IV infusion (max 1 mg/min) with the drug diluted in 500 to 1000 mL saline.13

Chlorpromazine is the only medication approved by the FDA for the treatment of intractable hiccups (it is not approved for this indication by Health Canada), but there are only observational data to support the use.1,6

May reverse the abnormal depolarization in the hiccup reflex arc.2

Concern about QTc prolongation, hypotension (especially with IV doses), others.4

Concern about movement disorders with prolonged use.12

Monitor blood pressure with IV administration.13

Haloperidol

2 mg to 5 mg IM,13,14 then
1 mg to 4 mg PO three times daily14

May be a safer alternative to IV chlorpromazine (less hypotension).13

Limited information (case reports, case series) to support use.10

Concern about QTc prolongation.4

Concern about movement disorders with prolonged use.12

Metoclopramide

10 mg PO or 5 mg to 10 mg IV/IM three to four times daily

Lower quality, small, randomized, controlled trials and case series available to support the use.1,4

May reduce the intensity of esophageal contractions.2

Concern about QTc prolongation.9

Concern about movement disorders with prolonged use.1

Theoretically, domperidone (Canada only) should be effective, but there are no studies supporting its use.1

GABA analogs

Baclofen

5 mg to 10 mg PO three times a day

Some experts consider baclofen a first-line therapy because during long-term therapy it’s less likely to cause adverse effects compared with antidopaminergic agents.1,2

Lower quality, small, randomized, controlled trials available to support the use.1

May reverse the abnormal depolarization in the hiccup reflex arc or affect GABA transmission.2

May cause drowsiness and dizziness.4

Gabapentin

900 mg to 1200 mg/day; in divided doses

Some experts consider gabapentin a first-line therapy because during long-term therapy it’s less likely to cause adverse effects compared with antidopaminergic agents.1

Only case series and case reports available to support the use.1

May enhance GABA transmission centrally.1

May cause drowsiness and dizziness.4

Antiepileptic agents

Carbamazepine

100 mg to 300 mg PO up to four times a day

Only case series and case reports available to support the use.1

May inhibit excitatory sodium channels on central neurons.1

May cause dizziness, nausea, vomiting.12

Phenytoin

100 mg PO three times daily

Use based on expert opinion; limited evidence to support the use.1

May inhibit excitatory sodium channels on central neurons.1

May cause dizziness, drowsiness.12

Valproate

Dose titration up to 20 mg/kg/day

Only case series and case reports available to support the use.1

May enhance GABA transmission centrally.1,2

May cause dizziness, drowsiness, nausea, vomiting.12

Miscellaneous Agents2

Nifedipine

20 mg to 60 mg/day PO

Only case series and case reports available to support the use.1

May reverse the abnormal depolarization in the hiccup reflex arc.2

Amitriptyline

25 mg to 100 mg/day PO

Use based on expert opinion; limited evidence to support the use.1

Proton pump inhibitors (omeprazole, others)

GERD treatment doses11

One large case series of proton pump inhibitors showed benefit in patients with hiccups related to gastroesophageal reflux disease. However, there was no control group and it is not known if the hiccups were due to GERD or if hiccups were the cause of GERD.1

Other medications which have been tried for hiccups include midazolam, clonazepam, pramipexole, olanzapine, amantadine, sertraline, risperidone, methylphenidate, viscous lidocaine and methylcellulose.7,8

Km
September 9, 2017

Good article , gives many practical remedies for medicine related hiccups.

Glen
September 8, 2017

To get rid of hiccups, stand up and arch your head backward to stretch/ tighten the abdominal muscles. Put hands behind your head & hold that position for 30-60 seconds. Works for me.

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