Chronic Nausea and Vomiting Syndromes

Educational Objectives

The goal of this program is to improve management of chronic nausea and vomiting syndromes. After hearing and assimilating this program, the clinician will be better able to:

1. Interpret gastric emptying studies to personalize treatment for gastric neuromuscular dysfunction.
2. Differentiate chronic nausea vomiting syndrome, cyclic vomiting syndrome, and cannabinoid hyperemesis syndrome using Rome 4 criteria.

Summary

Gastric neuromuscular dysfunction as unified framework: traditional paradigm separated functional dyspepsia and gastroparesis as distinct entities; emerging evidence supports consolidation under single umbrella term "gastric neuromuscular dysfunction"; both conditions share cardinal symptoms including nausea, vomiting, epigastric pain, postprandial fullness, early satiety, and bloating; unified approach enables more rational phenotyping and treatment personalization based on gastric emptying profiles and predominant symptoms rather than arbitrary diagnostic boundaries

Evidence supporting unified framework: pivotal 2021 prospective trial enrolled ≈1000 patients over 48 wk comparing functional dyspepsia (normal gastric emptying) versus gastroparesis (delayed gastric emptying); symptom analysis—nausea and vomiting prevalence and severity were equivalent between groups, presenting symptoms could not differentiate the two conditions; histopathologic analysis—both groups demonstrated similar neuropathologic changes on gastric biopsy, including decreased interstitial cells of Cajal (pacemaker cells controlling gastric motility) and reduced cell density in myenteric plexus compared with controls; gastric emptying variability—among patients with baseline delayed gastric emptying, 60% remained delayed at 48 wk but 40% completely normalized (median retention improving from 25% to 3% at 4 hr); conversely, ≈40% of patients with baseline normal gastric emptying developed delayed emptying by 48 wk; this fluidity demonstrates gastric emptying represents a phenotypic spectrum rather than static diagnostic category

High-quality gastric emptying study methodology: standardized meal consists of 4 oz egg whites, 2 pieces toasted white bread, jam, and water (Tougas meal); provides most physiologic and reproducible data; troubleshoot potential issues before ordering; egg allergy—most patients allergic to egg yolk not egg white; celiac disease—patient may bring gluten-free bread; technique involves radiolabeled egg whites with nuclear medicine scanning over 4 hr measuring meal retention at specified time points

Gastric emptying study interpretation: rapid gastric emptying defined as <30% meal retention at 1 hr; delayed gastric emptying defined as >10% retention at 4 hr; severely delayed gastric emptying defined as >20% retention at 4 hr; gastric emptying halftime often reported by radiologists but not reliable metric, especially with delayed emptying; clinicians should interpret results using percent retention at 1-hr and 4-hr time points for accurate patient counseling

Management approach for delayed gastric emptying: foundational interventions include glycemic control (maintain blood glucose consistently <275 mg/dL, as higher levels naturally slow gastric motility), medication review to eliminate agents delaying gastrointestinal (GI) motility (glucagon-like peptide-1 [GLP-1] agonists, opiates, anticholinergics), dietary modifications emphasizing small particle-sized diet (anything mashable with fork) incorporating low-fat and low-fiber principles, antiemetics such as ondansetron as needed

Pharmacologic treatments for delayed gastric emptying: metoclopramide—only Food and Drug Administration (FDA)-approved treatment, available in oral, suspension, or intranasal formulations; suspension or intranasal forms preferred when significant vomiting present to ensure therapeutic delivery; erythromycin—macrolide antibiotic with motilin agonist properties providing pure prokinetic effect; prescribe 3 wk on, 1 wk off to prevent tachyphylaxis and allow receptor reset

Alternative agents for delayed gastric emptying: selection based on guideline recommendations and concomitant symptoms; prucalopride—global prokinetic agent for patients with comorbid constipation, FDA-approved for chronic idiopathic constipation with robust data supporting benefit in delayed gastric emptying; aprepitant—neurokinin-1 antagonist for predominant nausea/vomiting, FDA-approved for chemotherapy-induced nausea with demonstrated benefit in gastroparesis; nortriptyline—tricyclic antidepressant for patients with predominant abdominal pain; mirtazapine—tetracyclic antidepressant for patients with nausea and weight loss

Refractory delayed gastric emptying: advanced therapies include enteral nutrition via jejunostomy tube, parenteral nutrition in severe cases; pyloric-directed interventions include pyloric botulinum toxin injection or gastric peroral endoscopic myotomy (G-POEM), which involves endoscopic submucosal tunneling through stomach with pyloromyotomy achieving ≈70% clinical success rate

Management for normal or rapid gastric emptying: acid suppression—proton pump inhibitors and histamine-2 receptor antagonists (famotidine) as first-line therapy, beneficial through anti-secretory properties and immune response modification in gastric and duodenal mucosa; neuromodulators—tricyclic antidepressants (nortriptyline, amitriptyline), mirtazapine especially with weight loss, duloxetine and pregabalin for uncomfortable fullness or pain; motility agents—buspirone (5-hydroxytryptamine-1 [5-HT1] antagonist) improves fundic accommodation, particularly beneficial for rapid gastric emptying and bothersome postprandial fullness; anticholinergic antispasmodics (dicyclomine) for rapid gastric emptying; Th2 response modulators—best evidence in pediatric populations with supportive meta-analysis data in adults, including histamine-1 blockers (ketotifen) or leukotriene antagonist (montelukast); over-the-counter options—peppermint oil (commonly branded as IBgard)

Rome IV diagnostic criteria for chronic nausea vomiting syndrome (CNVS): bothersome nausea at least 1 day/wk and/or ≥1 vomiting episode/wk; exclusion of self-induced vomiting, eating disorders, and rumination syndrome required for diagnosis

Rome IV diagnostic criteria for cyclic vomiting syndrome (CVS): stereotypical episodes of vomiting with consistent pattern regarding onset and duration; episodes typically begin in early morning hours with severe vomiting (up to 30 episodes daily) lasting <1 wk; diagnostic requirements include ≥3 episodes in past year with episodes separated by ≥1 wk; patients generally asymptomatic between episodes (mild nausea or pain acceptable but should feel well inter-ictally)

Rome IV diagnostic criteria for cannabinoid hyperemesis syndrome (CHS): presents identically to CVS but occurs in patients with heavy cannabis use defined as ≥4 uses/wk for several years; symptomatic improvement requires sustained cannabis cessation for ≥6 mo, which may require substantial patient counseling and motivation

Treatment for CNVS: antiemetics including ondansetron, metoclopramide, and aprepitant; cannabinoids such as cannabidiol demonstrate evidence for symptom control; neuromodulators including mirtazapine, nortriptyline, or amitriptyline

Abortive therapies for CVS: patients should initiate treatment at earliest recognition of episode onset; sublingual ondansetron; rectal promethazine; benzodiazepines (alprazolam); diphenhydramine; intranasal or subcutaneous triptans (sumatriptan)

Prophylactic therapies for CVS: indicated for moderate to severe disease defined as >4 episodes annually or episodes requiring emergency department visits or intravenous (IV) fluid resuscitation; tricyclic antidepressants as first-line, specifically amitriptyline at higher doses than typically used for other disorders of gut-brain interaction (target 1.5 mg/kg body weight, typically 70 to 125 mg nightly, compared with 10 to 25 mg for irritable bowel syndrome); second-line options for patients intolerant or non-responsive to tricyclic antidepressants include topiramate, zonisamide, levetiracetam, aprepitant; limited evidence supports supplements including coenzyme Q10 and riboflavin

Treatment for CHS: cannabis cessation is primary, secondary, and tertiary intervention; for patients unwilling to cease cannabis use, prophylactic therapy with tricyclic antidepressants may provide benefit; abortive therapy options mirror CVS treatment with addition of topical capsaicin applied anywhere on body (commonly abdomen) to trigger transient receptor potential vanilloid 1 (TRPV1) receptors, mimicking therapeutic effect of hot showers frequently used by these patients; olanzapine demonstrates evidence for acute episode management

Avoidant restrictive food intake disorder (ARFID) comorbidity: eating disorder characterized in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) by restrictive or avoidant food intake based on sensory concerns or fear of aversive consequences rather than body image or weight concerns; 2024 Gastroenterology study demonstrated 33% of patients with disorders of gut-brain interaction meet ARFID screening criteria; among patients specifically with functional dyspepsia or gastric neuromuscular dysfunction, prevalence increases to 56%; female patients have 1.3 odds ratio for comorbid ARFID; identification important as these patients benefit from multidisciplinary care involving gastroenterologist, dietitian, and psychologist or psychiatrist

Readings

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Adkins' lecture includes information related to the off-label or investigational use of erythromycin, prucalopride, aprepitant, nortriptyline, and mirtazapine in management of delayed gastric emptying.

Acknowledgements

Dr. Adkins was recorded at the 8th Annual Jefferson Women and Gastroenterology Health Symposium, held on February 27, 2026, in Philadelphia, PA, and presented by Sidney Kimmel Medical College at Thomas Jefferson University. For information about upcoming CME activities from this presenter, please visit https://jefferson.cloud-cme.com/. AudioDigest thanks Dr. Adkins and Sidney Kimmel Medical College at Thomas Jefferson University for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

Lecture ID:

GE401101

Qualifies for:

ABIM MOC, Clinical Pharmacology

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.