What are the causes of chronic nausea?

From the Guidelines

Chronic nausea can be caused by various conditions, including gastrointestinal disorders, medication side effects, and systemic diseases, with opioids being a significant contributor, as seen in up to 50% of patients when opioids are initiated or the dose is increased greatly 1.

Causes of Chronic Nausea

Some common causes of chronic nausea include:

• Gastrointestinal disorders such as gastroesophageal reflux disease (GERD), peptic ulcer disease, gastroparesis, and functional disorders like functional dyspepsia or irritable bowel syndrome
• Medication side effects, particularly from opioids, antibiotics, chemotherapy drugs, and some antidepressants
• Systemic conditions like pregnancy, migraine headaches, vestibular disorders, hormonal imbalances, anxiety disorders, and central nervous system disorders
• Metabolic conditions such as diabetes, kidney disease, and liver disease ### Identifying and Addressing the Underlying Cause Treatment depends on identifying and addressing the underlying cause, which may require diagnostic tests like endoscopy, gastric emptying studies, or blood work.

Management of Chronic Nausea

Management often includes both treating the primary condition and using anti-nausea medications such as:

• Ondansetron (4-8mg every 8 hours)
• Promethazine (12.5-25mg every 4-6 hours)
• Metoclopramide (10mg before meals), which is recommended as first line for the management of chronic nausea, including opioid-related 1 Lifestyle modifications like eating smaller, more frequent meals, avoiding trigger foods, staying hydrated, and managing stress can also help reduce symptoms while the underlying cause is being addressed.

Opioid-Induced Nausea

For patients experiencing nausea due to opioid use, metoclopramide is recommended as the first-line treatment 1, with prevention strategies including pretreatment with metoclopramide or prochlorperazine around the clock for the first few days of opioid therapy, with gradual weaning of the antiemetic.

From the FDA Drug Label

It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine, and that the released serotonin then activates 5-HT3 receptors located on vagal efferents to initiate the vomiting reflex The causes of chronic nausea are not directly addressed in the provided drug labels. However, according to the dolasetron label, chemotherapeutic agents can produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine, which then activates 5-HT3 receptors to initiate the vomiting reflex 2.

• Chemotherapeutic agents may contribute to nausea and vomiting. No conclusion can be drawn about the causes of chronic nausea.

From the Research

Causes of Chronic Nausea

• Chronic nausea and vomiting can result from a variety of pathophysiological processes, involving both gastrointestinal and non-gastrointestinal causes 3
• Gastrointestinal causes of chronic nausea and vomiting include gastroparesis, cyclic vomiting syndrome, reflux esophagitis, duodenal ulcer, and functional dyspepsia 3, 4
• Non-gastrointestinal disorders that can cause chronic nausea and vomiting include medications, vestibular, and neurologic disorders, as well as hyperthyroidism 3, 4
• Central pathways of nausea and vomiting appear to be at least partly different, and nausea is no longer considered only a penultimate step of vomiting 5
• The central pathway of chronic nausea is different from that of acute nausea and closely resembles that of neuropathic pain 5

Underlying Mechanisms

• Nausea and vomiting result from continuous interactions among gastrointestinal, central nervous system, and autonomic nervous system 5
• Afferent pathways from the gastrointestinal tract via vagus, vestibular system, and chemoreceptor trigger zone project to nucleus tractus solitarius, which relays the signal to central pattern generator initiating multiple downstream pathways 5
• The central nausea pathway appears to be under constant modulation by autonomic nervous system and cerebral cortex 5

Prevalence and Impact

• The prevalence of chronic nausea and vomiting is unclear, although the epidemiology of specific conditions is better understood 3
• Chronic unexplained nausea affects approximately 0.6% of the population, and is more likely to report functional dyspepsia and irritable bowel syndrome 4
• Health-related quality of life is significantly lower in people with nausea occurring 'more than one day per week' in a general population 4