Can dexamethasone cause hiccups? Uncovering a surprising side effect

In a study of chemotherapy patients, the incidence of dexamethasone-induced hiccups was reported to be as high as 42%. While not common for all users, this surprising side effect can be distressing, particularly for those receiving high-dose or repeated courses of the corticosteroid.

Quick Summary

Dexamethasone can cause persistent hiccups by affecting the central nervous system's hiccup reflex arc. This adverse effect is more frequent in males and may be managed by discontinuation, steroid rotation, or other medications.

Key Points

• Dexamethasone can cause hiccups: It is a known but rare side effect, confirmed by multiple case reports and studies.

• Mechanism affects the brainstem: The drug is thought to lower the synaptic threshold in the midbrain, stimulating the hiccup reflex arc.

• Men are more susceptible: Studies show a strong male predominance among patients who experience dexamethasone-induced hiccups.

• Treatment involves several options: Management includes stopping the drug, rotating to another steroid, or using medications like metoclopramide or baclofen.

• Duration and severity vary: Hiccups can range from transient and mild to severe and persistent, lasting for days after the drug is stopped.

• Higher doses increase risk: High-dose dexamethasone, often used in chemotherapy, is more frequently associated with inducing hiccups.

• Alternative steroids are an option: For patients needing ongoing steroid therapy, switching to methylprednisolone can resolve hiccups without sacrificing antiemetic efficacy.

Understanding Dexamethasone's Role in Hiccups

Dexamethasone is a powerful corticosteroid with significant anti-inflammatory and immunosuppressive properties. It is widely used for treating conditions from allergic reactions and arthritis to cerebral edema and as an antiemetic for chemotherapy-induced nausea and vomiting (CINV). While generally well-tolerated, numerous case reports and studies have established a clear link between dexamethasone administration and the onset of hiccups, medically known as singultus. For some patients, these hiccups are not merely a minor annoyance but can become severe and persistent, causing significant discomfort, sleep deprivation, and disruption to daily life. The link is especially noted in patients receiving high-dose intravenous or oral dexamethasone, with symptoms often starting within hours of administration and resolving after the drug is discontinued.

Proposed Mechanism of Dexamethasone-Induced Hiccups

The exact mechanism for why dexamethasone can cause hiccups is still not fully understood, but it is believed to involve the central nervous system (CNS). Hiccups are a reflex action controlled by a complex neural pathway known as the hiccup reflex arc. This arc consists of an afferent (sensory) pathway, a central processing unit, and an efferent (motor) pathway.

Several theories have been proposed to explain how dexamethasone interferes with this pathway:

• Midbrain Stimulation: One widely accepted hypothesis suggests that dexamethasone, being highly lipophilic, can effectively cross the blood-brain barrier. Once in the brain, it may lower the synaptic transmission threshold in the midbrain, the location of the central hiccup reflex center. This increased excitability then triggers the reflex.
• Corticosteroid Receptor Binding: Another theory proposes that dexamethasone may competitively bind to specific corticosteroid receptors within the hiccup reflex arc, directly causing irritation and stimulation.
• Neurotransmitter Modulation: Changes in neurotransmitter activity may also play a role. The hiccup reflex arc is modulated by neurotransmitters like dopamine and gamma-aminobutyric acid (GABA). It has been suggested that corticosteroids could affect the balance of these neurotransmitters, thus inducing hiccups.

Risk Factors and Incidence

While dexamethasone-induced hiccups (DIH) are not a universal side effect, several factors have been identified that increase the likelihood of its occurrence:

• Male Predominance: Numerous studies and case reports have highlighted a striking male predominance in DIH cases. The exact reason for this gender difference is unclear, but it may be related to differences in steroid receptor distribution or function in the male brain.
• High Dosage: The risk and severity of hiccups appear to increase with higher doses of dexamethasone. The side effect is frequently reported in patients receiving high-dose therapy for conditions like multiple myeloma or as an antiemetic for chemotherapy.
• Concurrent Chemotherapy: Patients undergoing certain types of chemotherapy, particularly with agents like cisplatin, appear to have a higher risk of developing hiccups when combined with dexamethasone. The combination may have a synergistic effect on the hiccup reflex arc.
• Underlying Conditions: Some underlying conditions can predispose individuals to hiccups. When combined with dexamethasone, this can increase the risk. Examples include pneumonia, gastrointestinal issues, and neurological disorders.

A Comparison of Corticosteroids Regarding Hiccup Risk

Feature	Dexamethasone	Methylprednisolone / Prednisolone	Other Steroids	Remarks
Hiccup Incidence	Relatively higher, particularly in high doses and males.	Lower compared to dexamethasone.	Varies; case reports exist for other steroids, but dexamethasone has a stronger association.	Discontinuation or rotation from dexamethasone is often effective.
Blood-Brain Barrier (BBB) Permeability	Highly permeable to the BBB.	Less permeable to the BBB than dexamethasone.	Varies, depends on the specific steroid's properties.	Higher BBB permeability is a proposed reason for dexamethasone's higher hiccup risk.
Use in Chemotherapy	Standard component of antiemetic regimens.	Can be used as an alternative antiemetic in patients experiencing DIH.		Rotation is a key management strategy for chemotherapy patients.
Therapeutic Efficacy	Excellent anti-inflammatory and antiemetic properties.	Effective alternative, often used to prevent DIH without compromising antiemetic control.		Management involves balancing side effects with therapeutic needs.

Managing Dexamethasone-Induced Hiccups

Managing persistent hiccups caused by dexamethasone requires a careful approach, often involving a healthcare provider to weigh the benefits of continued steroid use against the patient's quality of life. Common management strategies include:

1. Discontinuation or Dosage Reduction: If medically appropriate, the most direct solution is to discontinue the dexamethasone. In many cases, hiccups resolve shortly after the drug is stopped. If therapy is necessary, reducing the dose may also alleviate the symptoms.

2. Steroid Rotation: For patients receiving dexamethasone for chemotherapy, switching to an equivalent dose of a different corticosteroid, such as methylprednisolone or prednisolone, has proven to be an effective strategy. Because these alternatives are less permeable to the blood-brain barrier, they have a lower risk of inducing hiccups while maintaining the required therapeutic effect.

3. Pharmacological Treatment: Several medications can be prescribed to manage persistent hiccups, including:

   • Metoclopramide: This anti-nausea drug has been successfully used to treat DIH.
   • Baclofen: A muscle relaxant that can be effective for intractable hiccups.
   • Gabapentin: An anticonvulsant medication that has shown success in some cases.
   • Chlorpromazine: An antipsychotic that is FDA-approved for hiccups, though it is typically reserved for more severe cases due to its potential side effects.

4. Non-Pharmacological Strategies: Simple remedies can offer relief for less severe hiccups. These include breath-holding, gargling with cold water, or swallowing a teaspoon of sugar. While not curative for drug-induced cases, they can provide temporary relief.

Conclusion

While not the most common side effect, the potential for dexamethasone to cause hiccups is a well-documented phenomenon. The mechanism is thought to involve the drug's effect on the central nervous system's hiccup reflex arc, particularly in the midbrain. The risk is more pronounced in males and with higher doses, especially in the context of chemotherapy. For patients experiencing this distressing side effect, effective management strategies are available. Options include discontinuation of the medication, switching to an alternative corticosteroid like methylprednisolone, or using other anti-hiccup medications. Recognition of this side effect is crucial for healthcare providers to ensure patient comfort and prevent unnecessary workups for the patient experiencing a drug-induced condition.

For more detailed clinical studies, including comparative effectiveness of steroid rotation, see the article Treatment of Dexamethasone‐Induced Hiccup in Chemotherapy Patients by Methylprednisolone Rotation.

Frequently Asked Questions

Are dexamethasone-induced hiccups a common side effect?

No, hiccups induced by dexamethasone are considered a rare side effect. However, they are a well-documented phenomenon in medical literature, particularly in specific patient populations.

Why does dexamethasone cause hiccups in some patients and not others?

The exact reason is unknown, but proposed mechanisms involve dexamethasone's ability to cross the blood-brain barrier and stimulate the hiccup reflex arc in the brainstem. Individual differences in susceptibility, such as gender, may play a role.

Is there a specific patient group more affected by dexamethasone-induced hiccups?

Yes, case reports and studies indicate a clear male predominance. Additionally, patients receiving higher doses of the medication, especially those undergoing chemotherapy, have a higher reported incidence.

How soon after taking dexamethasone can hiccups begin?

Hiccups can begin relatively quickly, often within a few hours to a day after receiving a dose of dexamethasone.

What is the primary treatment for dexamethasone-induced hiccups?

The most definitive treatment is discontinuation of the dexamethasone. If that is not possible, switching to another corticosteroid, such as methylprednisolone, or starting a medication like metoclopramide can be effective.

Can I use home remedies for dexamethasone-induced hiccups?

Simple home remedies like holding your breath or drinking cold water might offer temporary relief, but they are often insufficient for managing drug-induced hiccups. A persistent issue requires medical attention.

Will hiccups stop as soon as I stop taking dexamethasone?

Hiccups typically resolve after discontinuing dexamethasone, but the timeframe can vary. In some cases, persistent hiccups may continue for several days after the medication is stopped.