Cyclic Vomiting Syndrome Treatment

Treatment Strategy Based on Disease Severity

Patients with moderate-severe CVS (≥4 episodes/year lasting >2 days requiring ED visits or hospitalizations) require both prophylactic therapy with amitriptyline AND abortive therapy with sumatriptan plus ondansetron, while patients with mild CVS (<4 episodes/year lasting <2 days without ED visits) require only abortive therapy. 1, 2

Prophylactic Therapy (For Moderate-Severe CVS Only)

First-Line: Amitriptyline

Start amitriptyline 25 mg at bedtime and titrate slowly (10-25 mg increments every 2 weeks) to a goal dose of 75-150 mg nightly or 1-1.5 mg/kg at bedtime. 1, 2
Obtain baseline ECG before initiating therapy due to QTc prolongation risk. 1, 3
Slow titration is generally better tolerated than rapid dose escalation. 1
Amitriptyline achieves response rates of 67-75% in preventing CVS episodes. 3, 2
Dose at night to minimize daytime sedation and anticholinergic side effects (dry mouth, blurred vision, constipation, weight gain). 1

Second-Line Prophylactic Agents (If Amitriptyline Fails or Not Tolerated)

Topiramate: Start 25 mg daily, titrate to 100-150 mg daily in divided doses; monitor electrolytes and renal function twice yearly. 2
Levetiracetam: Start 500 mg twice daily, titrate to 1000-2000 mg daily in divided doses; monitor CBC. 2
Zonisamide: Start 100 mg daily, titrate to 200-400 mg daily; monitor electrolytes and renal function twice yearly. 2
Aprepitant (NK1 antagonist): 80 mg 2-3 times weekly for patients 40-60 kg, or 125 mg 2-3 times weekly for patients >60 kg; use as adjunctive therapy. 2

Abortive Therapy (For All CVS Patients)

Critical Timing Principle

The probability of successfully aborting a CVS episode is highest when medications are taken immediately at the onset of prodromal symptoms—patient education on recognizing this phase is imperative. 3, 2

Prodromal symptoms include impending sense of doom, panic, anxiety, restlessness, mental fog, fatigue, headache, diaphoresis, flushing, or bowel urgency. 3, 2
The prodromal phase typically lasts a median of 1 hour before the emetic phase begins. 2
Missing the prodromal window dramatically reduces abortive therapy effectiveness. 3, 2

Standard Abortive Regimen: Combination Therapy

Nearly all patients require two agents rather than monotherapy to reliably abort CVS attacks—use sumatriptan PLUS ondansetron together. 3, 2

Sumatriptan

20 mg intranasal spray in head-forward position to optimize anterior nasal receptor contact. 3, 2
Alternative: Subcutaneous injection for patients who cannot tolerate intranasal administration. 2
Can repeat once after 2 hours, maximum 2 doses per 24 hours. 3, 2

Ondansetron

8 mg sublingual tablet every 4-6 hours during the episode. 3, 2

Additional Abortive Agents (Use in Combination)

Promethazine: 12.5-25 mg oral/rectal every 4-6 hours. 2
Prochlorperazine: 5-10 mg every 6-8 hours or 25 mg suppository every 12 hours. 2
Alprazolam, lorazepam, or diphenhydramine: For sedation to truncate episodes; use caution in adolescents with substance abuse risk. 3, 2

Acute Episode Management (Emergency Department/Hospital)

Immediate Interventions

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. 2
Aggressive IV fluid replacement with 10% dextrose for rehydration and metabolic support. 3, 2
Ondansetron 8 mg IV every 4-6 hours as first-line antiemetic. 3, 2
IV ketorolac as first-line non-narcotic analgesia for severe abdominal pain (avoid opioids as they worsen nausea and carry addiction risk). 2
Electrolyte replacement, particularly potassium and magnesium. 3

Refractory Cases

Droperidol or haloperidol for cases not responding to initial therapy. 3, 2
IV benzodiazepines for sedation in a quiet, dark room—adequate sedation can truncate severe episodes. 3, 2
Inadequate sedation can worsen symptoms during acute episodes. 3

Essential Lifestyle Modifications (For All Patients)

All patients with CVS must implement non-pharmacological interventions regardless of disease severity. 3

Maintain regular sleep schedule and avoid sleep deprivation. 3, 2
Avoid prolonged fasting. 3, 2
Identify and avoid individual triggers (present in 70-80% of patients). 2
Implement stress management techniques. 3, 2
Common triggers include infections, psychological stress (including positive events), sleep deprivation, fasting, and travel disruptions. 2

Management of Comorbid Conditions

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

Migraine headaches are present in 20-30% of CVS patients and suggest shared pathophysiology. 1, 2
Postural orthostatic tachycardia syndrome is observed in a substantial subgroup and may relate to underlying pathophysiologic mechanisms. 1
Referral to psychiatry or psychology for cognitive behavioral therapy or mindfulness meditation is recommended. 3
Treating comorbid conditions improves overall functional status and reduces episode frequency. 1

Critical Diagnostic Consideration: Cannabis Use

Screen all patients (especially adolescents) for cannabis use before confirming CVS diagnosis, as cannabis use >4 times weekly for >1 year suggests cannabinoid hyperemesis syndrome (CHS) rather than CVS. 3, 2

Cannabis cessation for 6 months or at least 3 typical cycle lengths is required to retrospectively diagnose CHS. 3
Hot water bathing is commonly associated with CHS but may also be observed in a subset of CVS patients. 1
Do not stigmatize patients with cannabis use—offer abortive and prophylactic therapy even with ongoing use, as treatments can still be effective. 4

Recovery Phase Management

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

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. 3, 2
Do not underestimate CVS severity, as approximately one-third of adults with CVS become disabled. 3, 2
Do not overlook retching and nausea, as these symptoms are equally disabling as vomiting itself and require aggressive treatment. 3, 2
Do not misinterpret self-soothing behaviors (excessive water drinking, self-induced vomiting) as malingering—these are specific to CVS and provide temporary relief. 3, 2
Inadequate sedation can worsen symptoms during acute episodes. 3
Do not use antiemetics in suspected mechanical bowel obstruction, as this can mask progressive ileus. 4

Special Populations: Coalescent CVS

A subset of patients with severe CVS experience progressively longer and more frequent episodes, culminating in daily nausea and vomiting with few asymptomatic days. 1
These patients should be offered prophylactic therapy akin to moderate-severe CVS, although management remains challenging. 1
A careful history will reveal years of episodic nausea and vomiting before the coalescent phase. 1

What are the recommended acute and prophylactic treatment options and dosing for cyclic vomiting syndrome?

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