Cyclic Vomiting Syndrome Treatment & Management

Updated: Oct 31, 2018
  • Author: Thangam Venkatesan, MD; Chief Editor: Carmen Cuffari, MD  more...
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Approach Considerations

In the absence of known pathophysiology, treatment of cyclic vomiting syndrome (CVS) remains empiric. [16, 50] The following management strategies are used for CVS [30, 51] :

  • Avoidance of triggers

  • Prophylactic and abortive therapy

  • Supportive care during acute episodes

  • Family support

Consultation with a sympathetic gastroenterologist without drug therapy may decrease the frequency of vomiting episodes by as much as 70%. [48]


Avoidance of Triggers

In some cases of CVS, avoiding identified dietary triggers such as chocolate, cheese, and monosodium glutamate (MSG) can prevent episodes without the use of medication. [30] If psychological stressors trigger episodes, stress management techniques or benzodiazepine anxiolytics (eg, lorazepam or diazepam) may help to abort attacks in the early stages. However, avoiding common triggers such as car rides and infection may be impractical or impossible.

Sleep deprivation is also cited as a common trigger for patients with CVS and proper sleep hygiene should also be emphasized. Interestingly, a 70% decrease in frequency of episodes (placebo effect) on consultation and lifestyle changes without drug therapy has been noted. [7]


Prophylactic and Abortive Pharmacologic Therapy

Pharmacologic therapy is used to prevent episodes of vomiting or to decrease their frequency and also to abort or attenuate episodes once they begin. [52, 53, 67] Preventive medications are normally used in patients with more than a single episode of CVS per month. The mainstays of prophylactic therapy include the following:

  • Cyproheptadine

  • Amitriptyline

  • Anticonvulsants such as topiramate, zonisamide, and levetiracetam

  • Propranolol

  • Phenobarbital

  • Erythromycin

Medications used for aborting episodes include the following:

  • Ondansetron

  • Promethazine

  • Prochlorperazine

  • Triptans

Agents used in migraines, such as triptans, have also been effective in aborting attacks. If abortive therapy fails, supportive combinations such as ondansetron plus lorazepam or chlorpromazine plus diphenhydramine may attenuate an attack of cyclic vomiting in progress. [54] In September 2011, the US Food and Drug Administration (FDA) released an alert about the possibility of an increase in cardiac arrhythmias with the use of ondansetron, and monitoring the QT interval is recommended.

Daily prophylactic pharmacotherapy may be used to prevent episodes that occur more than once a month or if they are extremely severe and disabling (eg, lasting 3 days or longer). [55, 56] Most of these drugs are non-GI medications, such as antimigraine agents, anticonvulsants, neuroleptics, and prokinetic drugs. A family history positive for migraines predicts a high response rate (80%) to antimigraine medications; therefore, these agents are a logical first choice. [30]

The guidelines formulated by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) recommend cyproheptadine as first-line therapy in children younger than 5 years. However, cyproheptadine can cause substantial weight gain because of an increase in appetite. Amitriptyline is the first-line choice in children older than 5 years and adolescents. [30]

Although no randomized control trials have examined medications used in CVS, several open-label trials and retrospective studies support the use of amitriptyline as first-line therapy in patients with CVS who are older than 5 years. In an open-label study of 41 patients with CVS who were followed up for 1-2 years, long-term therapy with tricyclic antidepressants (TCAs) significantly reduced the frequency and duration of episodes and the number of emergency department (ED) visits and hospitalizations. [57]

In this study, 80% of patients reported overall improvement of symptoms; however, one third of the patients reported mild adverse effects that did not lead to discontinuance of the medication. [57] After 2 years of treatment, the frequency of episodes was reduced from 17.8 episodes per year to 3.3 episodes, and the duration of an episode decreased from 6.7 days to 2.2 days. The mean number of ED visits and hospitalizations decreased from 15 to 3.3 over 2 years.

In a study of 132 patients with CVS who had been monitored for 4 years, 17 subjects were identified as nonresponders to TCA therapy. [43] When compared with responders, nonresponders were significantly more likely to have a history of migraine, coexisting psychological disorders, chronic marijuana use, and reliance on narcotics for pain control between CVS episodes. These findings favor a multidisciplinary approach to these patients, with aggressive treatment of other comorbid illnesses.

One study used an Internet-based survey completed by subjects with CVS or their parents to assess the efficacy of coenzyme Q10 and amitriptyline. [58] In all, 72% of the 162 patients receiving amitriptyline and 68% of the 22 patients receiving coenzyme Q10 reported at least a 50% reduction in the frequency, duration, or severity of episodes. Patients receiving coenzyme Q10 did not have any side effects, whereas one half of the patients receiving amitriptyline reported side effects.

In this study, 21% of patients on amitriptyline discontinued treatment because of side effects. [58] The same author reported a high degree of efficacy with monitoring drug levels and titrating medications to achieve therapeutic levels in a small series of patients. [59] Combination therapy with amitriptyline and mitochondrial supplements such as coenzyme Q10 and L-carnitine were used in most of these patients.

In another study, 20 adult patients with CVS received zonisamide (median dosage, 400 mg/day) or levetiracetam (median dosage, 1000 mg/day) because TCAs alone were unsatisfactory as maintenance medications; at least moderate clinical response was reported in 15 subjects (75%), and 4 of these (20%) reported symptomatic remission during 9.5 ± 1.8 months of follow-up. [60] Newer antiepileptic agents appeared beneficial as maintenance medications for nearly three fourths of adults with CVS.

In a retrospective study of 101 adults with CVS, most patients (86%) responded to treatment with TCAs, anticonvulsants (topiramate), coenzyme Q10, and L-carnitine. [61] Nonresponse to therapy was associated with coalescence of symptoms, chronic opiate use, and more severe disease as characterized by longer episodes, a greater number of ED visits in the year before presentation, the presence of disability, and noncompliance on univariate analysis. On multivariate analysis, only compliance to therapy was associated with a response.

When prophylactic medication fails or is not taken because of the sporadic and infrequent occurrence of cyclic vomiting episodes (< 1/month), abortive agents may be taken at the onset of an attack to stop progression. These antinausea and antimigraine agents are best administered nasally, rectally, or parenterally because they are not usually tolerated by mouth during intractable emesis. [48]

Sumatriptan, a 5-hydroxytryptamine receptor 1B/1D (5-HT1B/1D) agonist used off label, has a 46% efficacy rate when administered either intranasally or subcutaneously. The subcutaneous route has fallen out of favor because of a severe associated burning sensation in the chest and neck. [62, 63]

Ondansetron, a 5-HT3 antagonist, is a potent and effective antiemetic that acts on the chemoreceptor zone in the brainstem. In CVS, it is more effective at a higher dose of 0.3-0.4 mg/kg every 6 hours and is rendered more effective in severe episodes with the use of a benzodiazepine or diphenhydramine as an adjunctive antinausea agent. [1] High-dose intravenous (IV) ondansetron has a 59% efficacy rate and ameliorates episodes more often than it aborts them.

Aprepitant, a promising tachykinin (NK-1)–receptor antagonist, is used for chemotherapy-induced emesis and could be of benefit for patients with CVS. [48]


Supportive Pharmacologic Therapy

When both prophylactic and abortive therapy fails, supportive care becomes an essential aspect of treatment during acute episodes.

IV glucose-containing fluids may diminish the severity of episodes by as much as 42%. [48] Glucose may serve as the active ingredient by truncating the ketosis. However, the abdominal pain may be severe enough to necessitate the use of nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotics once a surgical abdomen has been excluded. Caution must be exercised when narcotics are administered for moderate to severe pain and patients must be monitored to ensure that they do not become dependent on or addicted to these agents.

Chronic opiate use can result in hyperalgesia, for which various mechanisms have been proposed. Sustained morphine administration increased substance P (SP) and NK-1 receptor expression in the spinal dorsal. Morphine-induced hyperalgesia was reversed by spinal administration of NK-1 receptor antagonists in rats and mice and was observed in wild-type NK-1 receptor positive mice but not in NK-1 receptor knockout (KO) mice. [64]

The transient receptor potential vanilloid 1 (TRPV1) receptor, a molecular sensor of noxious heat, also plays an important role in the development of hyperalgesia. Administration of morphine via subcutaneously implanted morphine pellets elicited both thermal and tactile hypersensitivity in TRPV1 wild-type mice but not in TRPV1 KO mice. [65] Moreover, oral administration of a TRPV1 antagonist reversed both thermal and tactile hypersensitivity induced by sustained morphine administration in mice and rats.

Sedatives such as diphenhydramine, lorazepam, and chlorpromazine have been administered to permit sleep and to provide temporary respite from unrelenting nausea. [48] The combination of lorazepam and ondansetron appears to be more effective than ondansetron alone.


Family Support

Families are encouraged to contact the Cyclic Vomiting Syndrome Association, which is an international voluntary organization that serves the needs of CVS patients in the United States and Canada, for ongoing support and information. Various resources, including local support groups and scientific and family conferences, are available to help families understand this disorder and to provide them with coping mechanisms for battling this often disabling illness.



A study that evaluated the relationship between anxiety and health-related quality of life in children and adolescents with cyclic vomiting syndrome (CVS) reported that children and adolescents with CVS appear to be at increased risk for anxiety. Anxiety symptoms are a stronger predictor of health-related quality of life than disease characteristics in children and adolescents with CVS. Assessment and treatment of anxiety in children and adolescents with CVS may have a positive impact on health-related quality of life. [66]