What type of antiemetic is haloperidol? A Comprehensive Guide

October 10, 2025 •

4 min read

Haloperidol is a first-generation antipsychotic medication belonging to the butyrophenone class, which, by acting as a potent dopamine antagonist, is also highly effective as an antiemetic. Its anti-nausea and vomiting properties have made it a valuable tool in managing specific, often refractory, cases of emesis.

Quick Summary

Haloperidol is a butyrophenone-class dopamine D2 receptor antagonist that exerts its antiemetic effects primarily by blocking receptors in the chemoreceptor trigger zone. It is used to manage and prevent various forms of nausea and vomiting, particularly when other treatments fail or are inappropriate.

Key Points

Butyrophenone Class: Haloperidol is classified as a butyrophenone, a type of first-generation (typical) antipsychotic with potent antiemetic properties.
Mechanism of Action: It primarily works as a dopamine (D2) receptor antagonist, blocking these receptors in the brain's chemoreceptor trigger zone (CTZ) to inhibit the vomiting reflex.
Refractory Nausea: Haloperidol is often used for severe or persistent nausea and vomiting that does not respond to other standard antiemetic medications.
Clinical Uses: Key applications include managing breakthrough nausea in chemotherapy patients, treating postoperative nausea, and providing symptom relief in palliative care. It is also effective for conditions like cannabis hyperemesis syndrome.
Dosage and Administration: Lower doses are used for antiemetic purposes compared to psychiatric uses to mitigate side effects. It can be administered orally, intramuscularly (IM), or intravenously (IV).
Important Side Effects: Notable adverse effects include extrapyramidal symptoms (involuntary movements), QTc prolongation (affecting heart rhythm), and sedation.
Safety Considerations: Caution is advised in patients with heart conditions or pre-existing movement disorders, and side effects should be closely monitored.

What is Haloperidol as an antiemetic?

Haloperidol is a first-generation, typical antipsychotic that belongs to the butyrophenone class of medications. While its primary indication is for psychiatric conditions like schizophrenia, its potent action on dopamine receptors gives it significant antiemetic properties. In clinical settings, it is often utilized off-label for managing severe nausea and vomiting that is unresponsive to other standard antiemetics. The use of haloperidol for this purpose, particularly at lower doses than those for psychiatric treatment, has a long history and is supported by clinical practice in areas like emergency medicine and palliative care.

Mechanism of action: Blocking the vomiting center

Haloperidol's antiemetic effect is directly linked to its function as a dopamine receptor antagonist. The key to understanding this mechanism lies in the chemoreceptor trigger zone (CTZ), an area located in the brainstem that acts as a sensory center for the vomiting reflex. The CTZ is rich in dopamine D2 receptors.

When toxins, certain drugs (like chemotherapy agents or opioids), or other substances trigger nausea, they can activate the CTZ by stimulating these D2 receptors. Haloperidol works by:

Binding to and blocking these dopamine D2 receptors in the CTZ.
Preventing the signal from the CTZ from reaching the central vomiting center, which is responsible for coordinating the physical act of vomiting.
Interrupting the emetic pathway before it can fully initiate, thereby controlling both the sensation of nausea and the act of vomiting itself.

This makes haloperidol particularly effective for managing nausea caused by circulating toxins or drugs, where the emetic signal originates centrally in the CTZ rather than peripherally in the gut.

Therapeutic applications of haloperidol as an antiemetic

Although not typically a first-line agent, haloperidol is a critical tool for managing various forms of severe nausea and vomiting. Its applications are most prominent in situations where other antiemetics have failed.

Use in palliative and cancer care

Patients with advanced cancer or in palliative care frequently experience multifactorial and difficult-to-control nausea and vomiting. Haloperidol is a commonly used and recommended treatment in this setting, often reserved for cases that are refractory to more common agents.

Breakthrough and postoperative nausea

For patients undergoing chemotherapy, haloperidol is an option for treating breakthrough nausea and vomiting that occurs despite prophylactic antiemetic treatment. It has also been shown to be effective in preventing and treating postoperative nausea and vomiting (PONV).

Specialized conditions

Haloperidol has demonstrated efficacy in managing specific conditions, including:

Cannabis Hyperemesis Syndrome (CHS): An increasingly recognized condition where chronic cannabis use leads to cyclical episodes of severe nausea and vomiting.
Diabetic Gastroparesis: A condition where the stomach's ability to empty itself is delayed, causing persistent nausea and vomiting.
Emergency Medicine: Used for undifferentiated nausea and vomiting in the emergency department, with some studies showing it to be superior to ondansetron for specific presentations.

Administration and potential side effects

Haloperidol for antiemetic purposes is typically administered at much lower doses than for psychiatric indications. It can be given orally, intramuscularly, or intravenously, with onset of action varying depending on the route.

Possible side effects include:

Extrapyramidal Symptoms (EPS): Movement-related side effects such as dystonia (involuntary muscle contractions), akathisia (restlessness), or parkinsonism-like symptoms. These are more common at higher doses but can occur with antiemetic dosing as well.
QTc Prolongation: A change in the heart's electrical activity that can lead to a dangerous, irregular heart rhythm (torsades de pointes). ECG monitoring may be necessary, especially in patients with pre-existing heart conditions or electrolyte imbalances.
Sedation: A common side effect, especially in elderly patients.
Neuroleptic Malignant Syndrome (NMS): A rare but serious and potentially fatal condition characterized by fever, muscle rigidity, and altered mental status.

Comparison table: Haloperidol vs. other antiemetics


Feature	Haloperidol (Butyrophenone)	Ondansetron (Serotonin Antagonist)	Metoclopramide (Dopamine Antagonist/Prokinetic)
Mechanism	Blocks dopamine (D2) receptors in the CTZ	Blocks serotonin (5-HT3) receptors, mainly peripherally	Blocks dopamine (D2) receptors (central and peripheral) and promotes gastric motility
Class	First-generation (typical) antipsychotic	Serotonin receptor antagonist	Dopamine receptor antagonist
Common Uses	Refractory N/V (e.g., palliative care, gastroparesis), breakthrough CINV	First-line for CINV, PONV, gastroenteritis	Gastroesophageal reflux (GERD), diabetic gastroparesis, CINV
Onset	Rapid, especially with IM/IV administration (20-40 min)	Rapid with IV administration (minutes)	Rapid with IV administration (1-3 min)
Key Side Effects	Extrapyramidal symptoms (EPS), QTc prolongation, sedation, NMS	Headache, constipation, QTc prolongation	EPS, tardive dyskinesia (long-term), sedation

Conclusion

Haloperidol is a powerful antiemetic medication, primarily acting as a dopamine D2 receptor antagonist within the brain's chemoreceptor trigger zone. This mechanism effectively controls nausea and vomiting, especially in challenging clinical situations like palliative care, breakthrough chemotherapy-induced emesis, and specific gastrointestinal disorders. While its efficacy is well-documented, its use is carefully managed due to a significant side effect profile, which includes extrapyramidal symptoms and the risk of QTc prolongation. As such, it is typically reserved for cases where other, less potent antiemetics have proven insufficient. Despite being a first-generation antipsychotic, its antiemetic application at lower doses remains a vital tool for physicians treating severe nausea and vomiting. The specific circumstances of its use and potential side effects necessitate careful monitoring and patient selection by healthcare professionals.

For additional pharmacological information, consult reputable resources like the National Institutes of Health (NIH).

Frequently Asked Questions

Haloperidol works by blocking dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) of the brain. The CTZ is responsible for triggering the vomiting reflex in response to certain chemical signals, and by blocking these receptors, haloperidol effectively prevents the signal from reaching the brain's vomiting center.

No, haloperidol is not typically used as a first-line antiemetic due to its potential for serious side effects, such as extrapyramidal symptoms and QTc prolongation. It is usually reserved for cases of severe or refractory nausea and vomiting that do not respond to other treatments.

Common side effects include sedation, dizziness, constipation, dry mouth, and, most notably, extrapyramidal symptoms (involuntary muscle movements, restlessness, stiffness). A more serious, though rare, risk is QTc prolongation, which can affect heart rhythm.

For antiemetic purposes, haloperidol is administered at much lower doses than those used for psychiatric indications like schizophrenia. Using a low dose helps to minimize the risk of side effects while still providing an effective anti-nausea effect.

Yes, haloperidol can be used for CINV, particularly for breakthrough nausea and vomiting that occurs despite initial prophylactic treatment with other antiemetics. Guidelines sometimes recommend it as a second-line or salvage agent for this purpose.

Yes, studies and clinical experience have shown haloperidol to be an effective treatment for cannabis hyperemesis syndrome (CHS), a condition characterized by cyclic episodes of severe nausea and vomiting in chronic cannabis users.

Haloperidol is commonly used in palliative care to manage nausea and vomiting, especially when the cause is multifactorial and not well-controlled by other therapies. It is considered a cornerstone medication in many palliative care protocols.

The onset of action depends on the route of administration. Intramuscular (IM) injections work relatively quickly, in about 20 minutes, while oral tablets or liquid may take 1 to 2 hours to provide relief.