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

Treatment of Cyclic Vomiting Syndrome

Start amitriptyline 25 mg at bedtime as first-line prophylaxis for moderate-severe CVS (≥4 episodes/year lasting >2 days), titrating to 75-150 mg nightly, and educate patients to take sumatriptan 20 mg intranasal spray plus ondansetron 8 mg sublingual immediately at prodromal symptom onset to abort episodes. 1

Disease Severity Classification Determines Treatment Intensity

Moderate-severe CVS requires both prophylactic and abortive therapy, defined as ≥4 episodes per year, each lasting >2 days, with at least one emergency department visit or hospitalization. 1, 2

Mild CVS requires only abortive therapy, defined as <4 episodes per year, each lasting <2 days, without emergency department visits. 1, 2

Approximately one-third of adults with CVS become disabled, making aggressive treatment essential for moderate-severe disease. 1

Prophylactic Therapy (Inter-Episodic Phase)

First-Line: Amitriptyline

• Initiate at 25 mg at bedtime and increase by 10-25 mg every 2 weeks to a target of 75-150 mg nightly (goal dose 1-1.5 mg/kg). 1, 2 This gradual titration optimizes efficacy while limiting side effects. 1

• Obtain a baseline electrocardiogram before starting to screen for QTc prolongation risk. 1, 2

• Administer at night to reduce daytime sedation and anticholinergic adverse effects (dry mouth, blurred vision, constipation, weight gain). 1

• Response rates are 67-75% in clinical studies. 1, 2, 3

Second-Line Prophylactic Agents

If amitriptyline fails or is not tolerated, consider these alternatives:

• 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

In pediatric patients, cyproheptadine is also considered standard prophylaxis alongside amitriptyline. 4

Abortive Therapy (Prodromal Phase)

Critical Timing Principle

The probability of successfully aborting an episode is highest when medications are taken immediately at the onset of prodromal symptoms. 1, 2, 3 Missing this window dramatically reduces effectiveness. 1, 2

Patient Education on Prodromal Recognition

Educate patients to recognize their stereotypical prodromal symptoms, which may include: 1, 2

• Impending sense of doom or panic
• Anxiety or restlessness
• Diaphoresis (occurs in 70-80% of patients) 1
• Mental fog or fatigue
• Headache
• Bowel urgency
• Flushing

The prodromal phase lasts a median of 1 hour before vomiting begins. 1, 3

Standard Abortive Regimen

Combination therapy with sumatriptan plus ondansetron is the standard abortive regimen—nearly all patients require two agents rather than monotherapy to reliably abort CVS attacks. 1, 2, 3

• 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, 2 Subcutaneous injection is an alternative route if intranasal is not tolerated. 1

• Ondansetron 8 mg sublingual tablet every 4-6 hours during the episode. 1, 2

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 truncate episodes; use caution in adolescents with substance abuse risk. 1, 2

Acute Episode Management (Emetic Phase)

Emergency Department Interventions

When home abortive therapy fails, immediate ED management includes: 1, 2, 3

• Place patient in a quiet, dark room immediately to minimize sensory stimulation, as patients in the emetic phase are often agitated and have difficulty communicating. 1, 3

• Aggressive IV fluid replacement with 10% dextrose-containing fluids for rehydration and metabolic support. 1, 2

• 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. 1 Avoid opioids—they worsen nausea and carry high addiction risk. 1

• IV benzodiazepines for sedation. 1, 2

• Electrolyte replacement—check and correct abnormalities immediately. 1, 3

Refractory Cases

For patients not responding to initial therapy, use droperidol or haloperidol as dopamine antagonists. 1, 2, 3 Multiple concurrent agents with different mechanisms of action may be necessary, administered around-the-clock rather than PRN. 3

Ketorolac Precautions

Exercise caution with ketorolac in: 1

• Patients over 60 years
• Compromised fluid status
• History of peptic ulcer disease
• Significant alcohol use
• Receiving nephrotoxic medications

Discontinue NSAIDs if BUN or creatinine doubles or if hypertension develops or worsens. 1

Recovery Phase Management

Focus on rehydration with electrolyte-rich fluids (sports drinks) and gradual introduction of nutrient drinks as tolerated with small, frequent sips. 1, 2, 3

Essential Lifestyle Modifications (All Patients)

Implement these non-pharmacological interventions regardless of disease severity: 1, 2

• Maintain regular sleep schedule and avoid sleep deprivation
• Avoid prolonged fasting
• Identify and avoid individual triggers—stress is a trigger in 70-80% of CVS patients (including positive stressors such as birthdays and vacations) 1
• Implement stress management techniques

Common triggers include hormonal fluctuations (menstrual cycle), travel, motion sickness, acute infections, surgery, and intense exercise. 1

Management of Comorbid Conditions

Screen all CVS patients for anxiety, depression, and panic disorder—psychiatric comorbidities are present in 50-60% of patients, and treating underlying anxiety can decrease CVS episode frequency. 1, 2, 3 Referral to psychiatry or psychology for cognitive behavioral therapy or mindfulness meditation is recommended. 2

A personal or family history of migraine (present in 20-30% of CVS patients) supports CVS diagnosis and may guide treatment selection. 1, 3

Postural orthostatic tachycardia syndrome (POTS) is observed in a substantial subgroup of CVS patients, suggesting overlapping autonomic dysfunction. 1

Critical Diagnostic Distinction: Cannabis Use

Screen all patients (especially adolescents) for cannabis use before confirming CVS diagnosis—cannabis use ≥4 times weekly for >1 year suggests cannabinoid hyperemesis syndrome (CHS) rather than CVS. 1, 2, 3 If cannabis use criteria are met, the working diagnosis should be changed from CVS to CHS, and definitive treatment requires cessation of cannabis use. 1

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. 1, 3 Cannabis cessation for 6 months or at least 3 typical cycle lengths is required to retrospectively diagnose CHS. 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 that for moderate-severe CVS (e.g., amitriptyline). 1 A thorough history typically reveals years of episodic nausea/vomiting preceding the coalescent phase. 1

Common Pitfalls to Avoid

• Missing the prodromal window dramatically reduces abortive therapy effectiveness—educate patients and families to recognize early warning signs and take medications immediately. 1, 2, 3

• Do not misinterpret self-soothing behaviors (excessive water drinking, self-induced vomiting) as malingering—these are specific to CVS and provide temporary relief. 1, 3

• Do not overlook retching and nausea—these symptoms are equally disabling as vomiting itself and require aggressive treatment. 1, 3

• Do not use abdominal pain to exclude CVS—abdominal pain is present in most CVS attacks. 1

• Inadequate sedation can worsen symptoms during acute episodes. 2, 3

• Do not underestimate CVS severity—approximately one-third of adults with CVS become disabled. 1, 3

Pediatric-Specific Considerations

In young children, prodromal symptoms are present in approximately 65% of cases but may manifest as restlessness, behavioral changes, or symptoms that younger children cannot verbalize. 1 Identifiable triggers are found in 70-80% of children with CVS, underscoring the importance of systematic trigger assessment. 1

Nutritional supplements such as carnitine and coenzyme Q10 have shown efficacy in decreasing episodes and severity in small pediatric studies with high tolerability. 4