What is the recommended diagnostic approach and acute and prophylactic treatment for cyclic vomiting syndrome?

Cyclic Vomiting Syndrome: Diagnostic and Treatment Approach

Diagnostic Criteria and Clinical Recognition

Diagnose CVS using Rome IV criteria: stereotypical episodes of acute-onset vomiting lasting <7 days, at least 3 discrete episodes in the past year (with 2 in the prior 6 months), separated by at least 1 week of baseline health, and absence of vomiting between episodes. 1, 2

Key Diagnostic Features to Identify

• Stereotypical pattern is essential: Each patient's episodes must be identical in timing, duration, and associated symptoms—this consistency is the diagnostic cornerstone 1, 2
• Prodromal symptoms occur in ~65% of patients and include impending sense of doom, panic, anxiety, diaphoresis, flushing, mental fog, restlessness, headache, or bowel urgency, typically lasting a median of 1 hour before vomiting onset 1, 2
• Episodes most commonly begin in early morning hours (pre-dawn) 1
• Abdominal pain is present in most patients and should not exclude the diagnosis 1, 2
• Personal or family history of migraine is present in 20-30% of CVS patients and supports the diagnosis 1, 2

Initial Diagnostic Workup

Perform targeted laboratory testing: Complete blood count, serum electrolytes and glucose, liver function tests, serum lipase, urinalysis, and urine drug screen for cannabis 2

Screen all patients for cannabis use before confirming CVS diagnosis: Cannabis use >4 times weekly for >1 year suggests cannabinoid hyperemesis syndrome (CHS) rather than CVS, requiring 6 months of cessation to differentiate 1, 2

• Critical distinction: Hot water bathing occurs in 48% of CVS patients who don't use cannabis, so this behavior alone does not distinguish CHS from CVS 3

Screen for psychiatric comorbidities: Anxiety, depression, and panic disorder are present in 50-60% of CVS patients, and treating underlying anxiety can decrease episode frequency 1, 3, 2

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Disease Severity Classification

Classify CVS severity to determine treatment intensity 1, 3:

• Mild CVS: <4 episodes/year, each lasting <2 days, no ED visits or hospitalizations—requires only abortive therapy 1, 3
• Moderate-severe CVS: ≥4 episodes/year, lasting >2 days, requiring ED visits or hospitalizations—requires both prophylactic and abortive therapy 1, 3

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Prophylactic Therapy (For Moderate-Severe CVS)

Start amitriptyline as first-line prophylactic agent: 25 mg at bedtime, titrating up to 75-150 mg nightly (goal dose 1-1.5 mg/kg), with 67-75% response rate. 1, 3

• Obtain baseline ECG due to QTc prolongation risk 1

Second-Line Prophylactic Options

If amitriptyline is ineffective or not tolerated 1:

• Topiramate: Start 25 mg daily, titrate to 100-150 mg daily in divided doses; monitor electrolytes and renal function twice yearly
• Levetiracetam: Start 500 mg twice daily, titrate to 1000-2000 mg daily in divided doses; monitor CBC
• Zonisamide: Start 100 mg daily, titrate to 200-400 mg daily; monitor electrolytes and renal function twice yearly

Adjunctive Prophylactic Therapy

• 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

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Abortive Therapy (Prodromal Phase)

Educate patients to recognize their stereotypical prodromal symptoms and take medications immediately—the probability of aborting an episode is highest when medications are taken at the very onset of prodromal symptoms. 1, 3

Standard Abortive Regimen

Administer sumatriptan 20 mg intranasal spray PLUS ondansetron 8 mg sublingual at the first sign of prodromal symptoms. 1

• Sumatriptan: Can be repeated once after 2 hours (maximum 2 doses per 24 hours); administer in head-forward position to optimize nasal receptor contact; subcutaneous injection is an alternative route 1
• Ondansetron: Can be given 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): Can help truncate episodes; use caution in adolescents with substance abuse risk 1

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Emergency Department/Acute Episode Management

If home abortive therapy fails, immediate ED interventions include 1, 3:

Initial Stabilization

• Place patient in quiet, dark room to minimize sensory stimulation, as patients in the emetic phase are often agitated and have difficulty communicating 1, 3
• Check and correct electrolyte abnormalities immediately 3
• Aggressive IV fluid replacement with dextrose-containing fluids for rehydration and metabolic support 1

Pharmacologic Management

• Ondansetron 8 mg IV every 4-6 hours as first-line antiemetic 1, 2
• 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—avoid opioids as they worsen nausea and carry addiction risk 1, 2
  • Caution: Exercise caution in patients >60 years, with compromised fluid status, history of peptic ulcer disease, or receiving nephrotoxic medications due to renal and GI toxicity risk 1
• IV benzodiazepines for sedation in a quiet, dark room 1, 3

Refractory Cases

• Droperidol or haloperidol for patients not responding to initial therapy 1, 3
• Multiple concurrent agents with different mechanisms may be necessary, administered around-the-clock rather than PRN 3

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Recovery Phase Management

Focus on rehydration with electrolyte-rich fluids (sports drinks or nutrient drinks) and gradual introduction of small, frequent sips as tolerated 3

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Essential Lifestyle Modifications (For All Patients)

Implement the following lifestyle modifications 1, 2:

• Maintain regular sleep schedule and avoid sleep deprivation
• Avoid prolonged fasting
• Identify and avoid individual triggers—identifiable triggers are found in 70-80% of patients, including infections, psychological stress (including positive events), sleep deprivation, and travel-related disruptions 1
• Stress management techniques

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Critical Pitfalls to Avoid

• Missing the prodromal window dramatically reduces abortive therapy effectiveness—patient education on recognizing prodromal symptoms is essential 1, 3
• Do not misinterpret self-soothing behaviors (excessive water drinking, self-induced vomiting) as malingering—these are characteristic coping responses in CVS 1, 3
• Do not overlook retching and nausea—these symptoms are equally disabling as vomiting itself and require aggressive treatment 1, 3
• Do not underestimate severity—approximately one-third of adults with CVS become disabled 3, 2
• Failing to recognize the stereotypical pattern is the most common diagnostic pitfall—episodes must be similar in onset, duration, and symptoms for each individual patient 2
• Do not dismiss abdominal pain as excluding CVS—it is present in most patients 1, 2