What is the role of medications in the treatment of cyclic vomiting syndrome?

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

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]


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