From the Guidelines
For patients with cyclical vomiting syndrome who do not respond to ondansetron, the next step is to try sumatriptan, either via nasal spray or subcutaneous injection, in combination with another antiemetic agent, such as promethazine or prochlorperazine, to abort the episode. This approach is based on the most recent evidence from the 2024 AGA clinical practice update on diagnosis and management of cyclic vomiting syndrome, which suggests that combinations of two agents are often necessary to reliably abort CVS attacks 1. The use of sumatriptan and an antiemetic agent is a common abortive treatment regimen for CVS, and inducing sedation with agents like promethazine, diphenhydramine, or benzodiazepines may also be effective 1.
Some key points to consider when treating patients with CVS who do not respond to ondansetron include:
- The importance of early intervention, ideally during the prodromal phase, to increase the chances of aborting the episode
- The potential benefits of using sedating agents, such as promethazine or benzodiazepines, to induce sedation and help abort the episode
- The need for individualized treatment approaches, taking into account the patient's specific symptoms, medical history, and previous responses to treatment
- The potential role of other medications, such as anticonvulsants or mitochondrial supplements, in preventing or treating CVS episodes
In terms of specific treatment algorithms, the following steps can be considered:
- If the patient is experiencing an acute episode, try sumatriptan via nasal spray or subcutaneous injection, in combination with promethazine or prochlorperazine
- If the patient is unable to abort the episode at home, consider presentation to an emergency department for intravenous fluids and abortive therapy
- For prevention of episodes, consider low-dose tricyclic antidepressants like amitriptyline, or anticonvulsants like topiramate or zonisamide, in addition to mitochondrial supplements like coenzyme Q10, L-carnitine, and riboflavin.
From the Research
Next Steps for Patients with Cyclical Vomiting Syndrome
For patients with cyclical vomiting syndrome who do not respond to ondansetron (Zofran), several alternative treatment options can be considered:
- Aprepitant: A neurokinin 1 receptor antagonist that has been shown to be effective in preventing chemotherapy-induced vomiting or postoperative emesis, and has been used successfully in a patient with severe cyclic vomiting syndrome who failed oral ondansetron therapy 2.
- Combination of ondansetron and sumatriptan: Recommended for abortion of an acute vomiting episode, but other agents such as aprepitant and sedative agents can be considered when vomiting is refractory to initial treatments 3.
- Amitriptyline and cyproheptadine: Remain the standard of care for prophylaxis, with nutritional supplements such as carnitine and coenzyme Q10 showing efficacy in decreasing episodes and severity in small studies 3.
- Chlorpromazine: Has been used successfully in a patient with resistant cyclic vomiting syndrome who did not respond to many other agents 4.
- Addressing underlying conditions: Nonresponse to standard therapy in adult cyclic vomiting syndrome patients may be associated with co-existing migraine headache, psychiatric disorder, chronic narcotic and marijuana use, which should be addressed aggressively when symptom exacerbations continue during attempts to induce remission 5.
Considerations for Treatment
When considering treatment options for patients with cyclical vomiting syndrome who do not respond to ondansetron, it is essential to:
- Assess for underlying conditions: Such as migraine headache, psychiatric disorder, chronic narcotic and marijuana use, which may be contributing to the nonresponse to standard therapy 5.
- Consider novel therapies: Such as aprepitant, which has shown promise in treating cyclic vomiting syndrome, and other agents targeting the endocannabinoid system, which may offer potential for transforming the care of these patients 2, 6.