Treatment for Chronic Nausea

Metoclopramide is recommended as first-line therapy for the management of chronic nausea due to its both central and peripheral effects. 1

Initial Assessment and Management

Rule out specific causes of nausea including constipation, CNS pathology, chemotherapy effects, radiation therapy, hypercalcemia, gastritis, gastroesophageal reflux, gastric outlet obstruction, bowel obstruction, and medication side effects 1
Check blood levels of medications that can cause nausea, such as digoxin, phenytoin, carbamazepine, and tricyclic antidepressants 1
For gastritis or gastroesophageal reflux, consider proton pump inhibitors or H2 receptor antagonists 1

Metoclopramide 10-20 mg PO three to four times daily is recommended as first-line therapy for chronic nausea 1
For patients with prior history of opioid-induced nausea, prophylactic treatment with antiemetics is highly recommended 1
Controlled-release metoclopramide formulations (40 mg every 12 hours) may provide better nausea control than immediate-release formulations (20 mg every 6 hours) 2

If nausea persists despite as-needed regimen, administer antiemetics around the clock for 1 week and then change to as-needed dosing 1
Consider adding a second agent with a different mechanism of action for persistent nausea 1:
- Dopamine receptor antagonists: haloperidol (0.5-2 mg PO every 6-8 hours), prochlorperazine (10 mg PO every 6 hours) 1
- Phenothiazines: prochlorperazine, thiethylperazine 1
- Serotonin (5-HT3) receptor antagonists: ondansetron (8 mg PO twice daily), granisetron 1
- Alternative agents: scopolamine, dronabinol, olanzapine 1

For nausea persisting longer than one week, reassess the cause and consider opioid rotation if opioid-induced 1
Corticosteroids (dexamethasone 2-8 mg) can be beneficial for reducing persistent nausea, particularly in combination with metoclopramide and ondansetron 1
Consider cannabinoids (dronabinol, nabilone) for refractory nausea 1
For patients with bowel obstruction, olanzapine may be especially helpful 1

Chronic nausea pathways may differ from acute nausea pathways and may resemble neuropathic pain mechanisms, potentially explaining why conventional antiemetics may be less effective for chronic nausea 3
Neuromodulators such as tricyclic antidepressants, gabapentin, olanzapine, benzodiazepines (lorazepam 0.5-2 mg), and cannabinoids may be effective for chronic nausea 1, 3
Metoclopramide should be used with caution due to risk of extrapyramidal symptoms and tardive dyskinesia, especially with prolonged use beyond 12 weeks 4

Alternative therapies such as acupuncture, hypnosis, and cognitive behavioral therapy can be considered as adjuncts to pharmacologic treatment 1
Maintain adequate fluid intake and consider small, frequent meals to help manage symptoms 5

Monitor for extrapyramidal symptoms with metoclopramide, especially in patients under 30 years of age 4
If using metoclopramide, treatment beyond 12 weeks should be avoided in all but rare cases where therapeutic benefit outweighs the risk of tardive dyskinesia 4
For persistent symptoms despite optimal management, consider referral to specialized palliative care services 1