Systemic review: the pathogenesis and pharmacological treatment of hiccups

Aliment Pharmacol Ther. 2015 Nov;42(9):1037-50. doi: 10.1111/apt.13374. Epub 2015 Aug 25.


Background: Hiccups are familiar to everyone, but remain poorly understood. Acute hiccups can often be terminated by physical manoeuvres. In contrast, persistent and intractable hiccups that continue for days or months are rare, but can be distressing and difficult to treat.

Aim: To review the management of hiccups, including a systematic review of reported efficacy and safety of pharmacological treatments.

Methods: Available articles were identified using three electronic databases in addition to hand searching of published articles. Inclusion criteria were any reports of pharmaceutical therapy of 'hiccup(s)', 'hiccough(s)' or 'singultus' in English or German.

Results: Treatment of 341 patients with persistent or intractable hiccups was reported in 15 published studies. Management was most effective when directed at the underlying condition. An empirical trial of anti-reflux therapy may be appropriate. If the underlying cause is not known or not treatable, then a range of pharmacological agents may provide benefit; however, systematic review revealed no adequately powered, well-designed trials of treatment. The use of baclofen and metoclopramide are supported by small randomised, placebo-controlled trials. Observational data suggest that gabapentin and chlorpromazine are also effective. Baclofen and gabapentin are less likely than standard neuroleptic agents to cause side effects during long-term therapy.

Conclusions: This systematic review revealed no high quality data on which to base treatment recommendations. Based on limited efficacy and safety data, baclofen and gabapentin may be considered as first line therapy for persistent and intractable hiccups, with metoclopramide and chlorpromazine in reserve.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Amines / therapeutic use*
  • Anticonvulsants / therapeutic use
  • Antipsychotic Agents / therapeutic use
  • Baclofen / therapeutic use*
  • Benzamides / therapeutic use
  • Chlorpromazine / therapeutic use*
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • GABA-B Receptor Agonists / therapeutic use
  • Gabapentin
  • Hiccup / drug therapy*
  • Hiccup / etiology
  • Hiccup / physiopathology*
  • Hiccup / therapy
  • Humans
  • Metoclopramide / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • gamma-Aminobutyric Acid / therapeutic use*


  • Amines
  • Anticonvulsants
  • Antipsychotic Agents
  • Benzamides
  • Cyclohexanecarboxylic Acids
  • GABA-B Receptor Agonists
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Baclofen
  • Metoclopramide
  • Chlorpromazine