What medications cause intractable hiccups (intractable singultus)?

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From the Guidelines

Chlorpromazine, a phenothiazine, is known to be used to treat intractable hiccups, but on the other hand, certain medications such as antipsychotics, particularly those with anticholinergic properties, may worsen or cause intractable hiccups.

Medications Causing Intractable Hiccups

Several medications can cause intractable hiccups, including:

  • Antipsychotics, due to their anticholinergic properties 1
  • Certain antibiotics, such as macrolides and fluoroquinolones, which can prolong the QT interval and potentially lead to hiccups 1
  • Antiemetics, like ondansetron and dolasetron, which can also prolong the QT interval 1
  • Other medications, including mood-stabilizing agents, antihistamines, and respiratory tract medications 1

Mechanism and Risk Factors

These medications can trigger hiccups by irritating the vagus or phrenic nerves, affecting the central nervous system's hiccup reflex arc, or causing electrolyte imbalances that disrupt normal diaphragm function. The risk of medication-induced hiccups varies based on dosage, individual sensitivity, and concurrent medical conditions.

Management and Treatment

If you develop persistent hiccups while taking any medication, don't stop the medication abruptly but consult your healthcare provider, who may adjust your dosage, switch to an alternative medication, or prescribe treatments specifically for the hiccups, such as chlorpromazine 1.

From the Research

Medications Causing Intractable Hiccups

There are several medications that can cause intractable hiccups, including:

  • Dopamine-blocking medications, such as haloperidol and chlorpromazine 2, 3
  • Certain antidepressants, such as amitriptyline 2
  • Anticonvulsants, such as gabapentin and valproic acid 2, 4
  • Muscle relaxants, such as baclofen and cyclobenzaprine 5, 2
  • Benzodiazepines, such as midazolam and lorazepam 5, 2

Mechanism of Action

The exact mechanism of action for these medications in causing intractable hiccups is not fully understood, but it is thought to involve the disruption of normal neurotransmitter activity in the brain and spinal cord 5, 4. For example, dopamine-blocking medications may interfere with the normal functioning of the phrenic nerve, which controls the diaphragm 2.

Treatment Options

Treatment options for intractable hiccups caused by medications include:

  • Discontinuing the offending medication, if possible 6
  • Trying alternative medications, such as baclofen or gabapentin, which have been shown to be effective in treating intractable hiccups 5, 2, 3
  • Using other pharmacological agents, such as metoclopramide or chlorpromazine, which have been reported to be effective in some cases 2, 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Systemic review: the pathogenesis and pharmacological treatment of hiccups.

Alimentary pharmacology & therapeutics, 2015

Research

Intractable Hiccups.

Current neurology and neuroscience reports, 2018

Research

Management of intractable hiccups: an illustrative case and review.

The American journal of hospice & palliative care, 2014

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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