What is the treatment for Cyclic Vomiting Syndrome (CVS)?

Treatment of Cyclic Vomiting Syndrome

The American Gastroenterological Association recommends amitriptyline 25-150 mg nightly as first-line prophylactic therapy for moderate-severe CVS (≥4 episodes/year lasting >2 days), combined with immediate abortive therapy using sumatriptan 20 mg intranasal plus ondansetron 8 mg sublingual at the first sign of prodromal symptoms. 1

Disease Severity Classification Determines Treatment Intensity

Treatment strategy depends entirely on CVS severity classification 1:

• Mild CVS (<4 episodes/year, each <2 days, no ED visits): Requires only abortive therapy 1
• Moderate-Severe CVS (≥4 episodes/year, >2 days duration, requiring ED visits): Requires both prophylactic AND abortive therapy 1

This classification system is critical because approximately one-third of adults with CVS become disabled, making aggressive treatment essential for moderate-severe disease 2

Phase-Specific Treatment Approach

CVS has four distinct phases requiring different management strategies 2:

Inter-Episodic Phase: Prophylactic Therapy

Start amitriptyline 25 mg at bedtime and titrate to goal dose of 1-1.5 mg/kg (typically 75-150 mg nightly) with 67-75% response rates. 1

• Obtain baseline ECG before initiating due to QTc prolongation risk 1
• This is the ONLY first-line prophylactic agent recommended by the AGA 1

Second-line prophylactic options when 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 patients 40-60 kg, or 125 mg 2-3 times weekly for patients >60 kg 1

Prodromal Phase: Abortive Therapy (The Critical Window)

The probability of successfully aborting an episode is highest when medications are taken IMMEDIATELY at the onset of prodromal symptoms—this is the most important teaching point for patients. 1

Missing this window dramatically reduces treatment effectiveness 1. Patients must be "rehearsed" on recognizing their stereotypical prodromal symptoms, which may include impending sense of doom, panic, fatigue, mental fog, restlessness, anxiety, headache, bowel urgency, diaphoresis, or flushing 2

Standard abortive regimen (nearly all patients require combination therapy, not monotherapy): 1

• Sumatriptan 20 mg intranasal spray in head-forward position to optimize anterior nasal receptor contact; can repeat once after 2 hours (maximum 2 doses per 24 hours) 1
  • Alternative: Subcutaneous injection for patients who cannot tolerate intranasal administration 1
• Ondansetron 8 mg sublingual every 4-6 hours during the episode 1

Additional abortive agents to add to the "abortive cocktail": 1

• 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, though use caution in adolescents with substance abuse risk 1

Emetic Phase: Emergency Department Management

When home abortive therapy fails, aggressive ED intervention is required 1:

• IV fluids with 10% dextrose for rehydration and metabolic support 1
• Electrolyte replacement (check and correct abnormalities immediately) 3
• IV ondansetron 8 mg every 4-6 hours 1
• IV ketorolac as first-line non-narcotic analgesia for severe abdominal pain 1
• IV benzodiazepines for sedation in a quiet, dark room 1, 3
• Droperidol or haloperidol for refractory cases not responding to initial therapy 1, 3

Patients in the emetic phase often appear agitated and have difficulty communicating—providers may need to rely on caregivers or a pre-established individualized treatment plan 2

Recovery Phase

• Rehydration with electrolyte-rich fluids (sports drinks) 1
• Gradual introduction of nutrient drinks as tolerated with small, frequent sips 1

Essential Lifestyle Modifications for ALL Patients

Regardless of disease severity, all CVS patients must implement these non-pharmacological interventions 1:

• Maintain regular sleep schedule and avoid sleep deprivation 1
• Avoid prolonged fasting 1
• Identify and avoid individual triggers 1
• Implement stress management techniques 1

Management of Psychiatric Comorbidities

Screen ALL patients for anxiety, depression, and panic disorder, as these are present in 50-60% of CVS patients. 1

Treating underlying anxiety can decrease CVS episode frequency 1. Many patients experience prodromal anxiety and an "impending sense of doom" before episodes begin 2, 3. Referral to psychiatry or psychology for cognitive behavioral therapy or mindfulness meditation is recommended 4

Critical Diagnostic Consideration: Rule Out Cannabinoid Hyperemesis Syndrome

Before confirming CVS diagnosis, screen ALL patients for cannabis use—cannabis use >4 times weekly for >1 year suggests cannabinoid hyperemesis syndrome (CHS) rather than CVS. 1

Cannabis cessation for 6 months or at least 3 typical cycle lengths is required to retrospectively diagnose CHS 4. However, hot water bathing is present in 48% of CVS patients who don't use cannabis, so this behavior alone does NOT distinguish CHS from CVS 3

Common Pitfalls to Avoid

• Missing the prodromal window: This dramatically drops abortive therapy effectiveness—patient education on immediate medication administration is imperative 1, 3
• Underestimating CVS severity: One-third of adults with CVS become disabled; aggressive treatment is essential 2, 3
• Overlooking retching and nausea: These symptoms are equally disabling as vomiting itself and require aggressive treatment 3
• Misinterpreting self-soothing behaviors: Excessive water drinking or self-induced vomiting are specific to CVS and provide temporary relief—these are NOT malingering 3
• Inadequate sedation during acute episodes: This can worsen symptoms 3
• Using monotherapy for abortive treatment: Nearly all patients require combination therapy (sumatriptan PLUS ondansetron) rather than single agents 1