What is the recommended prophylactic therapy for cyclic vomiting syndrome?

Prophylactic Therapy for Cyclic Vomiting Syndrome

First-Line Prophylactic Treatment

Amitriptyline is the first-line prophylactic agent for moderate-severe cyclic vomiting syndrome, starting at 25 mg at bedtime and titrating to a goal dose of 75-150 mg nightly (or 1-1.5 mg/kg). 1, 2

Indications for Prophylactic Therapy

Prophylactic therapy should be offered to patients meeting criteria for moderate-severe CVS, defined as: 1, 2

• ≥4 episodes per year
• Each episode lasting >2 days
• Requiring emergency department visits or hospitalizations

Patients with mild CVS (<4 episodes/year, lasting <2 days, no ED visits) require only abortive therapy, not prophylaxis. 2

Amitriptyline Dosing and Monitoring

• Starting dose: 25 mg at bedtime 1, 2
• Titration: Increase by 10-25 mg increments every 2 weeks 1
• Goal dose: 75-150 mg nightly or 1-1.5 mg/kg 1, 2
• Monitoring: Obtain baseline ECG due to QTc prolongation risk 1, 2
• Timing: Dose at night to leverage sedating effects 1
• Expected response rate: 67-75% 2

Common Adverse Effects of Amitriptyline

Anticipate anticholinergic and antihistaminergic effects including somnolence, dry mouth, blurred vision, constipation, and weight gain. 1 Slow titration is generally better tolerated than rapid dose escalation. 1

Second-Line Prophylactic Options

When amitriptyline fails or is not tolerated, consider these alternatives: 1

Topiramate

• Starting dose: 25 mg daily 1, 2
• Titration: Increase by 25 mg weekly 1
• Goal dose: 100-150 mg daily in divided doses 1, 2
• Monitoring: Check serum electrolytes and renal function twice annually 1, 2
• Contraindications: History of kidney stones (increases risk) 1
• Pregnancy: Must not be used 1
• Adverse effects: Cognitive dysfunction, paresthesia, headache, fatigue, mood problems 1
• Potential benefit: Associated with weight loss, which may be advantageous in patients with higher BMI 1

A 2019 randomized trial comparing amitriptyline to topiramate found amitriptyline superior in reducing attack duration (3.43 vs 4.90 days, P=0.017) and achieving complete cessation of attacks (68% vs 39%, P=0.016). 3 This supports amitriptyline as the preferred first-line agent.

Levetiracetam

• Starting dose: 500 mg twice daily 1, 2
• Titration: Increase by 500 mg daily every 2 weeks 1
• Goal dose: 1000-2000 mg daily in divided doses 1, 2
• Monitoring: Complete blood count 1, 2
• Adverse effects: CNS depression 1
• Advantage: No therapeutic drug monitoring required 1

Zonisamide

• Starting dose: 100 mg daily 1, 2
• Titration: Increase by 100 mg daily every 2 weeks 1
• Goal dose: 200-400 mg daily 1, 2
• Monitoring: Electrolytes and renal function twice annually 1, 2
• Adverse effects: Irritability, confusion, depression 1
• Caution: Increased kidney stone risk, associated with weight loss 1

Aprepitant (Neurokinin-1 Antagonist)

• Dosing: 125 mg 2-3 times weekly for adults >60 kg; 80 mg 2-3 times weekly for adults 40-60 kg 1, 2
• Adverse effects: Neutropenia, fatigue 1
• Drug interactions: Potential interference with oral contraceptive pills 1
• Practical barriers: Challenging to obtain insurance coverage for off-label CVS use; expensive 1
• Pregnancy: Safer option during pregnancy 1

Special Populations and Considerations

Coalescent CVS

Patients with coalescent CVS (progressive worsening with daily nausea/vomiting and loss of well periods) should receive prophylactic therapy similar to moderate-severe CVS, though management remains challenging. 1 These patients may meet Rome IV criteria for chronic nausea vomiting syndrome but have a historical pattern of episodic vomiting that preceded coalescent symptoms. 1

Cannabis Use Screening

Screen all patients for cannabis use before initiating prophylaxis. 1, 2 Cannabis use >4 times weekly for >1 year suggests cannabinoid hyperemesis syndrome rather than CVS and requires 6 months of cessation (or at least 3 typical cycle lengths) to retrospectively diagnose CHS. 1, 2 However, patients using cannabis should still be offered prophylactic therapy, as these treatments can be effective even with ongoing cannabis use. 1

Nutritional Supplements

Consider adjunctive mitochondrial support: 1

• Coenzyme Q10: 300-400 mg daily (monitor liver enzymes)
• Riboflavin: 200 mg twice daily

Critical Clinical Pitfalls

• Slow titration is essential: Rapid dose escalation of tricyclic antidepressants increases anticholinergic side effects and reduces adherence. 1
• Don't withhold treatment based on cannabis use: Even patients with ongoing cannabis use and diagnostic uncertainty between CVS and CHS deserve prophylactic therapy trials. 1
• Address comorbidities: Screen for and treat anxiety, depression, migraines, and sleep disorders, as these substantially impact CVS symptoms and quality of life. 1, 2
• Lifestyle modifications are foundational: All patients should maintain regular sleep schedules, avoid prolonged fasting, pursue stress management, and identify/avoid individual triggers. 1, 2