What are the treatment options for nausea?

Treatment of Nausea

For chronic nausea, start with metoclopramide 10-20 mg orally three to four times daily as first-line therapy, while for chemotherapy-induced nausea, use ondansetron 4-8 mg as first-line treatment. 1, 2

Treatment Algorithm Based on Etiology

Chronic Nausea (≥4 weeks duration)

• Metoclopramide is the first-line medication, dosed at 10-20 mg orally three to four times daily, working through dopamine receptor antagonism at the chemoreceptor trigger zone and prokinetic effects that address gastric stasis 1
• This is the only FDA-approved medication specifically for gastroparesis-related symptoms 1
• Alternative first-line options include:
  • Prochlorperazine 5-10 mg four times daily or 10 mg every 6 hours as needed 1
  • Haloperidol 0.5-1 mg every 6-8 hours for dopaminergic pathway targeting 1

Chemotherapy-Induced Nausea

• 5-HT3 receptor antagonists are first-line, specifically ondansetron 4-8 mg or granisetron 1 mg orally twice daily 2
• Add dexamethasone 4 mg daily to enhance antiemetic effect 2
• For highly emetogenic chemotherapy (cisplatin ≥50 mg/m²), a single 24 mg oral dose of ondansetron administered 30 minutes prior to chemotherapy resulted in 66% of patients completing 24 hours with zero emetic episodes 3

Opioid-Induced Nausea

• Prophylactic metoclopramide around the clock for the first few days when initiating opioids is recommended for patients with prior history of opioid-induced nausea 1, 2
• Alternative prophylactic options include prochlorperazine 5-10 mg every 6 hours or haloperidol 0.5-1 mg 2
• Tolerance typically develops within a few days to one week 1, 4

Radiation-Induced Nausea

• For upper abdominal radiation, use ondansetron 8 mg 2-3 times daily or granisetron 2 mg daily 2
• Consider adding dexamethasone for enhanced effect 2

Gastroparesis-Related Nausea

• Metoclopramide 5-20 mg three times daily as a prokinetic agent 2
• 5-HT3 antagonists (ondansetron 4-8 mg or granisetron) can be added 2

Vestibular/Motion Sickness

• Scopolamine transdermal patch 1.5 mg every 3 days 2
• Meclizine 12.5-25 mg three times daily 1

Anticipatory/Anxiety-Related Nausea

• Lorazepam 0.5-2 mg or alprazolam 0.25-0.5 mg three times daily 2, 4
• Behavioral therapy techniques including hypnosis with systematic desensitization and guided imagery 2, 4

Second-Line Therapy for Refractory Symptoms

When first-line therapy fails, add a 5-HT3 receptor antagonist or neurokinin-1 receptor antagonist:

• Ondansetron 4-8 mg twice or three times daily or granisetron 1 mg twice daily 1
• Aprepitant 80-125 mg daily, which blocks substance P in the nucleus tractus solitarius and area postrema 1, 2

Combination Therapy Strategy

For persistent nausea despite monotherapy, combine metoclopramide with corticosteroids:

• Metoclopramide plus dexamethasone 10 mg twice daily 1
• The combination of metoclopramide, ondansetron, and corticosteroids has proven particularly effective for refractory symptoms 1

Additional Therapeutic Options for Refractory Cases

• Atypical antipsychotics: Olanzapine for refractory nausea through multiple receptor antagonism 1
• Neuromodulators: Tricyclic antidepressants (amitriptyline 25-100 mg/day, nortriptyline 25-100 mg/day) or mirtazapine 7.5-30 mg/day 1
• Anticholinergic/antihistamine agents: Scopolamine 1.5 mg transdermal patch every 3 days 1

Critical Pitfalls and Monitoring

Metoclopramide carries significant risk of extrapyramidal side effects and tardive dyskinesia with chronic use, particularly in elderly patients 1, 5

• Monitor closely for akathisia that can develop at any time over 48 hours post-administration 6
• Decreasing the infusion rate can reduce the incidence of this adverse effect 6
• Treat akathisia with intravenous diphenhydramine 6

Both metoclopramide and serotonin antagonists can prolong the QT interval on ECG 5

• Domperidone doses above 10 mg three times daily are not recommended due to QT prolongation risk 1

Droperidol, while more effective than prochlorperazine or metoclopramide, carries an FDA black box warning regarding QT prolongation 6

• Its use should be limited to refractory cases 6

Promethazine is more sedating than other comparative agents and has potential for vascular damage upon intravenous administration 6

• May be suitable when sedation is desirable 6

Reassessment Before Escalating Therapy

Before escalating antiemetic therapy, reassess for:

• Constipation, bowel obstruction or impaction 1
• Electrolyte abnormalities 1
• CNS pathology or brain metastases 1
• Medication side effects from other drugs 1
• Gastroesophageal reflux (treat with proton pump inhibitors or H2 blockers if present) 1
• Consider opioid rotation if opioid-induced nausea persists beyond 1 week 2

Non-Pharmacologic Adjuncts

• Eating food at room temperature 1, 4
• Dietary consultation for persistent symptoms 1, 4
• Acupuncture, hypnosis, or cognitive behavioral therapy for refractory cases 1
• Fluid and electrolyte replacement 7
• Small, frequent meals and avoidance of trigger foods 7

Evidence Quality Considerations

Ondansetron may be preferred as first-line for undifferentiated nausea in the emergency department setting based on its safety profile—it is as effective as promethazine but not associated with sedation or akathisia 6. However, a Cochrane review found no convincing evidence of superiority of any particular drug over placebo in the ED setting, with participants receiving placebo often reporting clinically significant improvement, implying general supportive treatment such as intravenous fluids may be sufficient for many patients 8. This suggests that when etiology is unclear and symptoms are mild, supportive care alone may be reasonable before initiating pharmacotherapy 8.