How Antipsychotics Exhibit Antiemetic Effects
Antipsychotics possess antiemetic effects primarily by acting as dopamine receptor antagonists. The body's emetic response, or vomiting reflex, is controlled by a network of nerves and receptors, most notably the chemoreceptor trigger zone (CTZ) in the brainstem. The CTZ is rich in dopamine D2 receptors.
When a substance like chemotherapy, opioids, or a gastrointestinal toxin stimulates the CTZ, it triggers the brain's vomiting center. Antipsychotics, especially first-generation types, block these D2 receptors, preventing the activation of the vomiting reflex. Atypical antipsychotics, like olanzapine, have a broader antiemetic action, blocking not only dopamine receptors but also other key neurotransmitter receptors, including serotonin 5-HT2 and 5-HT3. This multi-receptor antagonism can provide a more comprehensive antiemetic effect and is particularly useful in complex cases like chemotherapy-induced nausea and vomiting (CINV).
Typical Antipsychotics with Antiemetic Properties
First-generation, or typical, antipsychotics are strong dopamine antagonists and were among the first medications used for their antiemetic effects. They are generally inexpensive and effective but carry a higher risk of extrapyramidal symptoms (EPS) due to their potent D2 blockade.
- Prochlorperazine (Compro®): This phenothiazine is widely used to treat severe nausea and vomiting. It is effective for various causes and is available in oral, rectal, and injectable forms. While it effectively blocks dopamine, its use is typically short-term due to the risk of side effects.
- Haloperidol (Haldol®): A high-potency typical antipsychotic, haloperidol is a powerful antiemetic, particularly useful in treating difficult-to-control nausea and vomiting in palliative care and emergency medicine. Studies have shown it to be superior to other antiemetics for certain types of nausea.
- Chlorpromazine (Thorazine®): Another low-potency phenothiazine, chlorpromazine has strong antiemetic effects and has been historically used to treat nausea and vomiting from various causes, including radiation therapy. It also has antihistaminic and anticholinergic properties that contribute to its antiemetic profile.
- Droperidol (Inapsine®): This butyrophenone has potent antiemetic effects and is used for treating postoperative nausea and vomiting. Its use is limited in some contexts due to concerns about QTc prolongation.
Atypical Antipsychotics with Antiemetic Properties
Second-generation, or atypical, antipsychotics generally cause fewer EPS side effects than their first-generation counterparts. Olanzapine is the most studied and utilized atypical antipsychotic for its antiemetic effects.
- Olanzapine (Zyprexa®): An atypical antipsychotic that has proven highly effective in treating and preventing chemotherapy-induced nausea and vomiting (CINV), including breakthrough and delayed emesis. It is recommended in national guidelines for CINV prophylaxis in combination with other antiemetics. Its efficacy stems from its broad receptor activity, blocking dopamine D1-D4, serotonin 5-HT2A, 5-HT2C, 5-HT3, and histamine H1 receptors. It is often used off-label for nausea in palliative care patients who have failed other therapies.
Comparison of Antipsychotic Antiemetics
| Medication (Class) | Primary Antiemetic Action | Use Case | Typical Side Effects | Extrapyramidal Symptoms (EPS) Risk |
|---|---|---|---|---|
| Prochlorperazine (Typical) | Strong D2 receptor antagonism | Severe nausea/vomiting, chemotherapy, migraine | Sedation, anticholinergic effects, orthostatic hypotension | Moderate to High |
| Haloperidol (Typical) | Potent D2 receptor antagonism | Refractory nausea/vomiting, palliative care, migraine | Sedation, QTc prolongation, EPS | High |
| Chlorpromazine (Typical) | Strong D2 antagonism, plus H1, M1 blockade | Refractory nausea, radiation, intractable hiccups | Sedation, hypotension, anticholinergic effects | Moderate |
| Olanzapine (Atypical) | D2 and 5-HT3 antagonism (multiple receptors) | Chemotherapy-induced nausea/vomiting (CINV), palliative care | Sedation, dry mouth, weight gain, orthostatic hypotension | Low |
Important Considerations and Side Effects
The use of antipsychotics for antiemetic purposes is a powerful therapeutic option but comes with significant considerations. Side effects can be pronounced and limit their routine use for general nausea. Healthcare providers must carefully weigh the benefits against the risks, especially when dealing with elderly patients or those on multiple medications.
- Extrapyramidal Symptoms (EPS): These are involuntary movements caused by dopamine receptor blockade. Typical antipsychotics carry a higher risk of EPS, including dystonia, akathisia (restlessness), and tardive dyskinesia, which can be irreversible.
- Sedation: Many antipsychotics cause drowsiness, which can be both a therapeutic effect and a limiting side effect, depending on the patient's needs.
- QTc Prolongation: Some antipsychotics, like haloperidol and droperidol, can prolong the QTc interval on an electrocardiogram, increasing the risk of potentially fatal cardiac arrhythmias.
- Anticholinergic Effects: Medications such as prochlorperazine and chlorpromazine can cause dry mouth, constipation, and blurred vision.
- Metabolic Effects: Atypical antipsychotics like olanzapine are associated with an increased risk of weight gain and metabolic changes, though this is less of a concern with short-term antiemetic use.
Conclusion
While primarily known for their psychiatric uses, several antipsychotic medications have potent antiemetic effects, offering crucial relief for severe or refractory nausea and vomiting. These effects are mediated through their antagonism of dopamine and other neurotransmitter receptors in the brain's vomiting centers. Typical antipsychotics like prochlorperazine and haloperidol are powerful but carry a higher risk of extrapyramidal side effects. Atypical antipsychotics, particularly olanzapine, provide a multi-receptor approach and have a lower risk of these movement disorders, making them valuable in complex cases like chemotherapy-induced emesis. Due to their significant side effect profiles, antipsychotics are generally reserved for when conventional antiemetics are ineffective. Patients and providers should carefully consider the risks and benefits to ensure safe and effective treatment. For more detailed clinical information on antiemetics, consult authoritative resources such as the Cleveland Clinic's guide on antiemetic drugs.
