The American Gastroenterological Association (AGA) released a comprehensive Clinical Practice Update on the diagnosis and management of cyclic vomiting syndrome in adult patients. The updated guidelines aimed to improve the recognition and treatment of this underdiagnosed condition.
Cyclic vomiting syndrome (CVS)—characterized by recurring episodes of intense nausea, vomiting, and retching separated by symptom-free intervals—was estimated to affect 2% of adults in the United States.
The new recommendations, published in Gastroenterology, provided detailed guidance on the diagnosis of CVS, emphasizing the use of Rome IV criteria such as stereotypical episodes of acute-onset vomiting lasting < 7 days, with at least three discrete episodes in a year and two in the prior 6 months, separated by at least 1 week of baseline health.
The guideline authors distinguished between mild and moderate-severe CVS. Mild CVS was defined as < 4 episodes/year, each lasting < 2 days, without emergency department (ED) visits or hospitalizations. Moderate-severe CVS involved ≥ 4 episodes/year, each lasting > 2 days, and requiring at least one ED visit or hospitalization.
Diagnostic recommendations included considering CVS in adult patients presenting with episodic bouts of repetitive vomiting and recognizing the four distinct phases of the condition: interepisodic, prodromal, emetic, and recovery. The guideline authors advised a basic diagnostic workup involving complete blood count, serum electrolytes and glucose, liver function testing, lipase, and urinalysis. One-time esophagogastroduodenoscopy or upper gastrointestinal imaging was suggested to exclude obstructive lesions. Further, repeated studies should be avoided and gastric emptying scans should not be ordered routinely, since few patients with CVS have delayed emptying and results obtained during an episode are uninterpretable.
The guideline authors noted that approximately 65% of patients with CVS experienced prodromal symptoms lasting a median of 1 hour before vomiting onset. Abdominal pain was reported to be present in most patients during a CVS episode. Episodes often occurred in the early morning hours, with stress identified as a common trigger—affecting 70% to 80% of patients.
Comorbid conditions, including mood disorders, migraines, and seizure disorders were present in a respective 50% to 60%, 20% to 30%, and 3% of patients. Hot water bathing or showering for symptom relief was common, with approximately 48% of non–cannabis users finding relief from this behavior.
A notable subset of patients with severe CVS experienced a worsening disease trajectory marked by increased episodic length and frequency with few if any asymptomatic days, known as coalescent CVS. Some of the patients at this stage may continue to have intermittent severe episodes but experience chronic nausea in between. Coalescent CVS could pose a major diagnostic challenge as a result of the lack of asymptomatic periods and/or clear episodic patterns. However, these patients universally showed a prior multiyear history of episodic nausea and vomiting before their coalescent phase.
For management, the guideline authors recommended lifestyle modifications to identify and mitigate triggers. Involvement of allied health services was advised to address comorbid conditions like anxiety, depression, migraines, and sleep disorders. Prophylactic therapy was also suggested for patients with moderate-severe CVS, with tricyclic antidepressants as first-line treatment. Specific dosages were provided: starting at 25 mg just before sleep, with a goal dosage of 75 to 150 mg or 1 to 1.5 mg/kg before sleep for any tricyclic antidepressant.
Second-line prophylactic agents included topiramate (with a goal dosage of 100 to 150 mg daily), zonisamide (with a goal dosage of 200 to 400 mg daily), levetiracetam (with a goal dosage of 1,000 to 2,000 mg daily), and aprepitant (with a goal dosage of 125 mg 2 to 3 times weekly for adults > 60 kg).
For abortive therapy, the guideline authors recommended early administration during the prodromal phase. Sumatriptan (20 mg intranasally or 6 mg subcutaneously, repeated once after 2 hours if needed) and ondansetron (8 mg sublingual every 4 to 6 hours during an episode) were suggested. Most patients required combinations of at least two agents to reliably abort CVS attacks. Sedation was identified as an effective abortive strategy, with options including promethazine, diphenhydramine, and benzodiazepines.
Regarding ED management, the update advised treating all patients presenting with uncontrolled retching and vomiting, regardless of suspicion for cannabinoid hyperemesis syndrome (CHS). IV ketorolac was suggested as a first-line nonnarcotic analgesic. The guideline authors suggested that most patients should be placed in a quiet, dark room, and treated with IV benzodiazepines for sedation as well as IV dextrose-containing fluids and antiemetic medication.
The updated guidelines addressed cannabis use in CVS patients, noting that it often raises concerns for CHS. The guideline authors proposed that CHS should be considered a subset of CVS when prolonged (> 1 year) and heavy cannabis use (> 4 times weekly) preceded symptom onset. They advised that all patients, including those with ongoing cannabis use, should be offered abortive and/or prophylactic therapy—as these treatments could still be effective.
The guideline authors highlighted significant knowledge gaps in CVS pathophysiology and natural history. They recognized racial disparities in clinical outcomes for patients with CVS and called for increased clinical research leveraging multicenter, standardized patient registries to advance the understanding and treatment of the disorder.
