Cyclic Vomiting Syndrome: Diagnostic Work-Up and Treatment
Diagnostic Criteria
Diagnose CVS when a patient presents with stereotypical episodes of acute-onset vomiting lasting <7 days, with ≥3 discrete episodes in the past year (≥2 in the prior 6 months), separated by at least 1 week of complete wellness between episodes. 1, 2
Key Clinical Features to Identify
- Stereotyped pattern: Each episode must be identical in timing, duration, and associated symptoms—this repetitive pattern is essential for diagnosis 1, 2
- Prodromal phase: Approximately 65% of patients experience warning symptoms lasting a median of 1 hour, including impending sense of doom, panic, anxiety, diaphoresis, mental fog, restlessness, or fatigue 1, 2
- Early morning onset: Most episodes begin in pre-dawn hours 1
- Abdominal pain: Present in the majority of patients and should not exclude the diagnosis 1, 2
Essential Diagnostic Work-Up
Screen every patient for cannabis use ≥4 times weekly for >1 year before confirming CVS, as this pattern indicates cannabinoid hyperemesis syndrome (CHS) rather than CVS. 1, 3 Note that hot-water bathing occurs in 48% of CVS patients without cannabis use, so this behavior alone does not distinguish CHS from CVS 1, 2
Obtain the following baseline laboratory tests:
- Complete blood count, serum electrolytes, glucose, liver function tests, lipase 1
- Urinalysis and pregnancy test in women of childbearing age 1
- Complement C3 and anti-dsDNA antibodies if systemic lupus erythematosus is suspected 1
Perform upper GI series if bilious vomiting is present to exclude malrotation with volvulus or other anatomic obstruction—this is a surgical emergency 3
Upper endoscopy and abdominal imaging are recommended to exclude organic causes 4
Severity Classification (Determines Treatment Intensity)
Mild CVS: <4 episodes/year, each lasting <2 days, no emergency department visits or hospitalizations 1, 2
Moderate-severe CVS: ≥4 episodes/year, each lasting >2 days, requiring at least one emergency department visit or hospitalization 1, 2
Treatment Approach by Disease Severity
Mild CVS: Abortive Therapy Only
Patients with mild CVS require only abortive therapy with sumatriptan plus ondansetron during the prodromal phase. 1
Moderate-Severe CVS: Both Prophylactic and Abortive Therapy
Patients with moderate-severe CVS require both prophylactic amitriptyline and abortive therapy with sumatriptan plus ondansetron. 1, 2
Prophylactic Therapy (For Moderate-Severe CVS)
First-Line: Amitriptyline
Start amitriptyline 25 mg at bedtime, increase by 10–25 mg every 2 weeks to a target of 75–150 mg nightly (goal dose 1–1.5 mg/kg). 1 This gradual titration optimizes efficacy while minimizing side effects 1
- Obtain baseline ECG before starting therapy to screen for QTc prolongation risk 1
- Administer at night to reduce daytime sedation and anticholinergic effects (dry mouth, blurred vision, constipation, weight gain) 1
- Response rate: 67–75% in clinical studies 1, 2
Second-Line Options (If Amitriptyline Fails or Is Not Tolerated)
Topiramate: Start 25 mg daily, titrate to 100–150 mg daily in divided doses; monitor electrolytes and renal function twice yearly 1
Levetiracetam: Start 500 mg twice daily, titrate to 1000–2000 mg daily in divided doses; monitor CBC 1
Zonisamide: Start 100 mg daily, titrate to 200–400 mg daily; monitor electrolytes and renal function twice yearly 1
Aprepitant (neurokinin-1 antagonist): 80 mg 2–3 times weekly for adolescents 40–60 kg; 125 mg 2–3 times weekly for adolescents >60 kg 1
Abortive Therapy (Prodromal Phase)
The highest probability of aborting an episode occurs when medications are administered immediately at the onset of prodromal symptoms—patient education to recognize their prodrome is critical. 1, 2
Standard Abortive Regimen
Sumatriptan 20 mg intranasal spray (can repeat once after 2 hours, maximum 2 doses per 24 hours) 1
- Administer in head-forward position to optimize nasal receptor contact 1
- Subcutaneous injection is an alternative if intranasal route is not tolerated 1
PLUS
Ondansetron 8 mg sublingual every 4–6 hours during the episode 1
Additional Abortive Agents
Promethazine 12.5–25 mg oral/rectal every 4–6 hours 1
Prochlorperazine 5–10 mg every 6–8 hours or 25 mg suppository every 12 hours 1
Sedatives (alprazolam, lorazepam, diphenhydramine) to truncate the episode; use caution in adolescents with substance abuse risk 1, 2
Acute Episode Management (Emergency Department/Emetic Phase)
Immediately place the patient in a quiet, dark room to minimize sensory stimulation, as patients in the emetic phase are agitated and have difficulty communicating. 1, 2
Acute Treatment Protocol
IV dextrose-containing fluids for aggressive rehydration and metabolic support 1, 2
Ondansetron 8 mg IV every 4–6 hours as first-line antiemetic 1
IV ketorolac 15–30 mg every 6 hours (maximum 5 days, daily maximum 120 mg) as first-line non-narcotic analgesia for severe abdominal pain 1
- Avoid opioids: They worsen nausea and carry high addiction risk 1
- Exercise caution with ketorolac in patients >60 years, with compromised fluid status, or receiving nephrotoxic medications due to renal and GI toxicity risk 1
IV benzodiazepines for sedation 1, 2
Check and correct electrolyte abnormalities immediately, as these are common complications of prolonged vomiting 2
Refractory Cases
Droperidol or haloperidol for patients not responding to initial therapy 1, 2
Multiple concurrent agents with different mechanisms of action may be necessary, administered around-the-clock rather than PRN 2
Recovery Phase Management
Prioritize rehydration with electrolyte-rich fluids (sports drinks) and gradual introduction of nutrient drinks as tolerated. 2
Management of Comorbid Conditions
Screen all CVS patients for anxiety, depression, and panic disorder—these psychiatric comorbidities are present in 50–60% of patients, and treating underlying anxiety can decrease CVS episode frequency. 1, 2
Personal or family history of migraine is present in 20–30% of CVS patients and supports the diagnosis 1, 2
Postural orthostatic tachycardia syndrome (POTS) is observed in a substantial subgroup of CVS patients, indicating overlapping autonomic dysfunction 1
Treating identified psychiatric or neurologic comorbidities improves overall functional status and reduces episode frequency 1
Essential Lifestyle Modifications
All patients require:
- Regular sleep schedule, avoiding sleep deprivation 1
- Avoiding prolonged fasting 1
- Stress management techniques (stress is a trigger in 70–80% of patients, including positive stressors like birthdays and vacations) 1
- Identifying and avoiding individual triggers (hormonal fluctuations, travel, motion sickness, acute infections, surgery, intense exercise) 1
Critical Pitfalls to Avoid
Missing the prodromal window dramatically reduces abortive therapy effectiveness—emphasize immediate medication administration at prodrome onset 1, 2
Do not misinterpret self-soothing behaviors (excessive water intake, self-induced vomiting) as malingering—these are characteristic coping mechanisms in CVS 1, 2
Do not exclude CVS based on the presence of abdominal pain—abdominal pain is present in most CVS attacks 1, 2
Do not underestimate CVS severity—approximately one-third of adults with CVS become disabled 1, 2
Retching and nausea are equally disabling as vomiting itself and require aggressive treatment 1, 2
Special Population: Coalescent CVS
A distinct subgroup experiences progressively longer and more frequent episodes, eventually leading to daily nausea and vomiting with few asymptomatic days 1
These patients should be managed with prophylactic therapy comparable to moderate-severe CVS (amitriptyline), acknowledging the heightened therapeutic challenge 1