What is the relationship between serotonin and nausea?

From the Guidelines

Serotonin can trigger nausea and vomiting through its action on 5-HT3 receptors in the gut and brain, and 5-HT3 receptor antagonists like ondansetron, granisetron, or palonosetron are highly effective in managing serotonin-related nausea. When serotonin levels increase, such as during chemotherapy, migraine attacks, or with certain medications like SSRIs, these receptors become activated, sending signals to the brain's vomiting center. To manage serotonin-related nausea, 5-HT3 receptor antagonists are recommended, with dosages such as ondansetron (4-8mg every 8 hours) 1, granisetron (1-2mg daily) 1, or palonosetron (0.25mg IV single dose) 1. These medications work by blocking serotonin from binding to 5-HT3 receptors, preventing the nausea cascade. For mild cases, non-pharmacological approaches like ginger (250mg four times daily), small frequent meals, and avoiding triggering foods can help.

Key Points to Consider

• Serotonin-related nausea is particularly common during the first weeks of SSRI treatment, when starting chemotherapy, or during acute migraine attacks.
• Understanding the connection between serotonin and nausea explains why medications that block serotonin's effects specifically at these receptors are so effective for treating nausea in these situations.
• The choice of 5-HT3 receptor antagonist may depend on the specific clinical context, with palonosetron being superior in preventing delayed emesis 1.
• Antiemetics are given prophylactically 30–60 min before the start of chemotherapy, and recommendations concern chemotherapy-naive patients 1.

Management of Serotonin-Related Nausea

• For mild cases, non-pharmacological approaches can be used.
• For more severe cases, 5-HT3 receptor antagonists are recommended, with the choice of medication depending on the specific clinical context.
• The dosages of these medications can vary, but examples include ondansetron (4-8mg every 8 hours), granisetron (1-2mg daily), or palonosetron (0.25mg IV single dose).

From the FDA Drug Label

Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: ... gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The relationship between serotonin and nausea is that serotonin syndrome, which can occur with the use of 5-HT3 receptor antagonists like ondansetron, may include nausea as one of its gastrointestinal symptoms 23.

From the Research

Relationship Between Serotonin and Nausea

• The release of serotonin from the enterochromaffin of the gastrointestinal tract can lead to nausea and vomiting, as it binds to 5-HT3 receptors 4.
• 5-HT3 receptor antagonists can ameliorate nausea and vomiting in various circumstances, including chemotherapy-induced nausea and vomiting (CINV), radiation-induced emesis (RIS), and postoperative nausea and vomiting (PONV) 4, 5, 6, 7.
• Serotonin receptor antagonists, such as ondansetron, have been shown to be effective in preventing nausea and vomiting associated with emetogenic chemotherapy 5, 6, 8.
• The efficacy and safety of 5-HT3 receptor antagonists have been compared in various studies, with results indicating similar efficacy among different agents, including ondansetron, granisetron, dolasetron, and tropisetron 6, 8.
• Palonosetron has been shown to have greater efficacy than ondansetron for delayed nausea and acute and delayed vomiting in some studies 8.

Mechanism of Action

• The mechanism of action of 5-HT3 receptor antagonists involves the inhibition of serotonin binding to 5-HT3 receptors, which are involved in the regulation of nausea and vomiting 4, 5.
• The use of 5-HT3 receptor antagonists has been shown to reduce the incidence of nausea and vomiting in patients undergoing chemotherapy and surgery 4, 5, 6, 7.

Clinical Applications

• 5-HT3 receptor antagonists are widely used in the prevention and treatment of nausea and vomiting associated with chemotherapy, radiation therapy, and surgery 4, 5, 6, 7, 8.
• The choice of 5-HT3 receptor antagonist may depend on individual patient factors, such as the type and severity of nausea and vomiting, as well as the specific clinical setting 8.