What anticonvulsant is recommended to prevent Cyclic Vomiting Syndrome (CVS)?

Anticonvulsants for Prevention of Cyclic Vomiting Syndrome

Tricyclic antidepressants are strongly recommended as first-line prophylactic medications for moderate-severe cyclic vomiting syndrome, while topiramate, zonisamide, and levetiracetam are effective second-line anticonvulsant options when tricyclics fail or are not tolerated. 1

When to Use Prophylactic Therapy

Prophylactic therapy is indicated for patients with moderate-severe CVS, defined as:

• More than 4 episodes per year
• Episodes lasting longer than 2 days
• Episodes requiring ED visits or hospitalizations

For patients with mild CVS (fewer than 4 episodes/year, each lasting less than 2 days, without ED visits), abortive therapy alone is appropriate.

First-Line Therapy

• Tricyclic antidepressants (TCAs) - The 2024 AGA Clinical Practice Update strongly recommends TCAs as first-line prophylactic medications 1
  • Examples include amitriptyline
  • TCAs have the strongest evidence base for CVS prophylaxis

Second-Line Anticonvulsant Options

When TCAs fail or are not tolerated, the following anticonvulsants are recommended as second-line agents:

1. Topiramate

   • Effective in 65% of patients in a retrospective study 2
   • Significantly reduces annual CVS episodes (18.1 to 6.2), ED visits (4.3 to 1.6), and hospitalizations (2.0 to 1.0)
   • Higher doses and longer use (≥12 months) associated with better response
   • Common side effects: cognitive impairment (13%), fatigue (11%), paresthesia (10%)
   • 32% discontinuation rate due to side effects

2. Zonisamide

   • Median dose: 400 mg/day 3
   • Shown to be effective in clinical experience
   • May cause side effects requiring medication switch

3. Levetiracetam

   • Median dose: 1000 mg/day 3
   • Combined data with zonisamide showed 75% of patients had at least moderate clinical response
   • 20% reported symptomatic remission during follow-up
   • Reduced vomiting episode frequency from 1.3 to 0.5 per month

Clinical Considerations for Anticonvulsant Selection

• Patient comorbidities:

  • Patients with anxiety may have poorer response to topiramate 2
  • Patients with migraine history may benefit from topiramate or other anticonvulsants due to shared pathophysiology 4

• Side effect profile:

  • Moderate to severe side effects occur in approximately 45% of patients on anticonvulsants 3
  • Consider switching between anticonvulsants if side effects occur
  • Only 1 in 20 patients had complete intolerance to anticonvulsant therapy 3

• Dosing considerations:

  • Higher doses of topiramate associated with better response 2
  • Longer duration of therapy (≥12 months) improves outcomes 2
  • Monotherapy may be more effective than combination therapy 2

Pitfalls and Caveats

• Diagnostic challenges:

  • Ensure proper diagnosis of CVS before initiating prophylactic therapy
  • Rule out other causes of cyclic vomiting (e.g., metabolic disorders, structural abnormalities)

• Treatment expectations:

  • Set realistic expectations - complete remission occurs in only about 20% of patients 3
  • Treatment goal is to reduce frequency and severity of episodes

• Cannabis use:

  • Consider cannabis use patterns when evaluating patients
  • Distinguish between CVS and cannabinoid hyperemesis syndrome (CHS)
  • Anticonvulsants may still be effective even with ongoing cannabis use 1

• Treatment monitoring:

  • Regular follow-up to assess efficacy and side effects
  • Consider medication switch if inadequate response after 2-3 months

• Evidence limitations:

  • Recommendations are based primarily on case series and expert opinion
  • No randomized, placebo-controlled trials available for anticonvulsants in CVS 1

Remember that lifestyle modifications (regular sleep, avoiding triggers, stress management) should accompany pharmacologic therapy for optimal outcomes in all patients with CVS.