Cyclic Vomiting Syndrome Treatment & Management

  • Author: Thangam Venkatesan, MBBS; Chief Editor: Carmen Cuffari, MD   more...
 
Updated: Apr 23, 2010
 

Medical Care

In the absence of known pathophysiology, treatment of cyclic vomiting syndrome (CVS) remains empiric.[18, 46] The following 5 management strategies are used for cyclic vomiting syndrome: avoidance of triggers, prophylactic pharmacotherapy, abortive therapy, supportive care during acute episodes, and family support.[29]

Pharmacologic therapy is used to prevent episodes of vomiting or to decrease their frequency. Other medications may be used to abort or attenuate episodes once they begin. Preventive medications are normally used in patients with more than a single episode of cyclic vomiting syndrome per month. The mainstays of prophylactic therapy include cyproheptadine, amitriptyline, propranolol, phenobarbital, and erythromycin. If abortive therapy fails, supportive combinations such as ondansetron plus lorazepam or chlorpromazine plus diphenhydramine may attenuate an attack of cyclic vomiting in progress.

In some instances, avoiding identified dietary triggers, such as chocolate, cheese, and monosodium glutamate (MSG) can prevent episodes without the use of medication.[29] If psychological stressors trigger episodes, stress management techniques or benzodiazepine anxiolytics (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. Interestingly, a 70% decrease in frequency of episodes (placebo effect) upon consultation and lifestyle changes without drug therapy has been noted.[10]

Daily prophylactic pharmacotherapy may be used to prevent episodes that occur more than once per month or if they are extremely severe and disabling (eg, lasting ≥ 3 d).[47, 48] 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.[29]

In an open-label experience, with efficacy defined as greater than 50% reduction in episode frequency or severity, propranolol, cyproheptadine, and amitriptyline were effective 57%, 39%, and 67% of the time, respectively.[35, 49] The NASPGHAN guidelines 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.[29] Phenobarbital demonstrated a 79% success rate in one open-label trial in children who did not have EEG changes.[50] Erythromycin, a gastric prokinetic agent, demonstrated a 75% success rate in one open-label study.[51]

Winner et al reported a significant reduction (>75%) in days with migraine headaches in patients receiving topiramate compared with placebo.[52] Topiramate is currently used anecdotally in patients with cyclic vomiting syndrome. Another small therapeutic trial using L-carnitine reported reduced episode frequency and neurologic symptoms in patients with cyclic vomiting syndrome.[53]

In adults few studies are available; in one study, the overall treatment response in 24 adult patients receiving amitriptyline (1 mg/kg/d) for at least 3 months indicated that 93% had decreased symptoms and 26% achieved full remission.[54]

In a study of 132 patients with cyclic vomiting syndrome who had been monitored for 4 years, 17 subjects were identified as nonresponders to therapy with tricyclic antidepressants.[42] When compared with responders, the nonresponders were significantly more likely to have a history of migraine (p < 0.05), coexisting psychological disorders (p < 0.05), chronic marijuana use (p < 0.05), and reliance on narcotics for pain control between cyclic vomiting syndrome episodes (p < 0.05). These findings favor a multidisciplinary approach to these patients, with aggressive treatment of other comorbid illnesses.

In a open-label study of 41 patients with cyclic vomiting syndrome who were followed up for 1-2 years, long-term therapy with tricyclic antidepressants significantly reduced the frequency and duration of episodes and the number of ED visits and hospitalization.[55] Eighty percent of patients reported overall improvement of symptoms; however, one third of the patients reported mild adverse effects that did not lead to discontinuation of the medication. The frequency of episodes was reduced form 17.8 episodes per year to 3.3 episodes after 2 years of treatment; the duration of an episode decreased form 6.7 days to 2.2 days. The mean number of ED visits and hospitalizations decreased from 15 to 3.3 over 2 years.

Using an internet-based survey completed by subjects with cyclic vomiting syndrome or their parents, the efficacy of coenzyme Q10 and amitriptyline was assessed.[56] Of 162 subjects administered amitriptyline and 22 subjects administered coenzyme Q10, 72% of patients receiving amitriptyline and 68% of 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 contrast to the findings by McCallum et al, 21% of patients on amitriptyline discontinued treatment due to side effects.

In another study, 20 adult patients with cyclic vomiting syndrome received zonisamide (median dose, 400 mg/d) or levetiracetam (median dose, 1000 mg/d) because tricyclic antidepressants 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. Newer antiepileptic agents appeared beneficial as maintenance medications for nearly three fourths of adults with cyclic vomiting syndrome.[57]

Abortive agents may be taken at the onset of an attack to stop progression when prophylactic medication fails or is not taken because of the sporadic and infrequent occurrence of cyclic vomiting episodes (< 1/mo). These antinausea and antimigraine agents are best administered nasally, rectally, or parenterally because they are not usually tolerated by mouth during intractable emesis.[44] 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.[58]

Ondansetron, a 5-hydroxytryptamine receptor 3 (5-HT3) antagonist, is a potent and effective antiemetic that acts on the chemoreceptor zone in the brainstem. In cyclic vomiting syndrome, 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 use of a benzodiazepine or diphenhydramine as an adjunctive antinausea agent.[1] High-dose intravenous ondansetron has a 59% efficacy rate and ameliorates episodes more often than it aborts episodes. Aprepitant, a promising tachykinin (NK-1)-receptor antagonist, is used for chemotherapy-induced emesis and could have benefit in cyclic vomiting syndrome.[44]

When both prophylactic and abortive therapy fail, supportive care becomes an essential aspect of treatment during acute episodes. Intravenous glucose-containing fluids may diminish the severity of episodes by as much as 42%.[44] Glucose may be the active ingredient by truncating the ketosis. However, the abdominal pain may be severe enough to require nonsteroid anti-inflammatory drugs (NSAIDs) or narcotics once a surgical abdomen has been excluded. Sedatives such as diphenhydramine, lorazepam, and chlorpromazine have been administered to permit sleep and to provide temporary respite from unrelenting nausea.[44] The combined use of lorazepam and ondansetron appears to be more effective than ondansetron alone.

Families are also encouraged to contact the Cyclic Vomiting Syndrome Association, which is an international voluntary organization that serves the needs of patients in the United States and Canada, for ongoing support and information.

Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Thangam Venkatesan, MBBS  Assistant Professor, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical College of Wisconsin

Thangam Venkatesan, MBBS is a member of the following medical societies: American Gastroenterological Association and Indian Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

B UK Li, MD  Professor of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Director, Pediatric Fellowships and Gastroenterology Fellowship, Medical Director, Functional Gastrointestinal Disorders and Cyclic Vomiting Program, Medical College of Wisconsin; Attending Gastroenterologist, Children's Hospital of Wisconsin

B UK Li, MD is a member of the following medical societies: Alpha Omega Alpha, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Seth Marcus, MD  Fellow, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Memorial Hospital, Northwestern University

Seth Marcus, MD is a member of the following medical societies: American Academy of Pediatrics and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Shikha Sundaram, MD  Fellow, Department of Gastroenterology, Hepatology and Nutrition, Children's Memorial Hospital of Chicago and Northwestern University

Shikha Sundaram, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association

Disclosure: Nothing to disclose.

Abhilasha Pandey, MBBS  Froedtert Hospital, Medical College of Wisconsin

Disclosure: Nothing to disclose.

Specialty Editor Board

Jayant Deodhar, MD  Associate Professor in Pediatrics, BJ Medical College, India; Honorary Consultant, Departments of Pediatrics and Neonatology, King Edward Memorial Hospital, India

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

David A Piccoli, MD  Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine

David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Steven M Schwarz, MD, FAAP, FACN, AGAF  Professor of Pediatrics, Children's Hospital at Downstate, SUNY-Downstate Medical Center

Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research

Disclosure: Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor; Johnson & Johnson, Inc. Grant/research funds Independent contractor

Chief Editor

Carmen Cuffari, MD  Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

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Cyclic versus chronic temporal patterns of recurrent vomiting. The number of emeses is plotted over a 2-month period. The chronic pattern, represented by a thin dashed line, has low grade on nearly a daily basis (eg, gastroesophageal reflux). The cyclic pattern, represented by a heavy solid line, involves high-intensity episodes intermittently once every several weeks (eg, cyclic vomiting syndrome).
Table 1. Characteristics of Emergency Department Visits in Patients With Cyclic Vomiting Syndrome
CharacteristicAdults



(n = 104)



Children



(n = 147)



Number of ED visits per patient with cyclic vomiting syndrome (Median)15 (range, 1-200)10 (range, 1-175)
Number of ED visits prior to a diagnosis of cyclic vomiting syndrome (Median)7 (Range, 1-150)5 (Range, 0-65)
Diagnosis not made in the ED89 (93%)119 (93%)
Diagnosis not recognized in the ED in patients with an established diagnosis of cyclic vomiting syndrome84 (88%)97 (80%)
Number of different ED visited (Mean ± standard deviation)4.69 ± 4.722.6 ± 2.42
Table 2. Clinical Features in Adults and Children with Cyclic Vomiting Syndrome[39]
Feature ChildrenAdults
Age of Onset4.8 y (Earliest, 6 d)35 y (Latest, 73 y)
Delay in Diagnosis2.6 y8 y
Female-to-Male Ratio57:4317:24
FrequencyEvery 2-4 wkEvery 3 mo
Duration (Mean)1-2 d (range, 1-10 d)6 d (range, 1-21 d)
Periodicity49%Not reported
Early Morning Onset42%50%
Stereotypical Episodes99%85%
Prodrome72%, 1.5 h93%
SymptomsNausea, anorexia, pallorNausea, epigastric pain
Recovery to Oral Feeding6 h24 h
Relieving FactorsDeep sleepHot bath/shower (56%)
Precipitating FactorsStress (47%), infection (31%)Menses (57%), anxiety
Comorbid conditionsAnxietyNot reported
Interepisodic nausea< 6%63%
Coalescence of EpisodesFew50%
Vomiting6/hr at peak, bile (81%)8.5/hr
Systemic SymptomsPallor, salivation, listlessnessIntense thirst (33%)
GI SymptomsAnorexia, nausea, diarrhea, abdominal painAbdominal pain, diarrhea
Neurologic SymptomsHeadache, photophobia, phonophobia, abdominal painIrritable, confused
Natural history≥ 28% progress to migraineNot reported
Family history82%57%
ComplicationsDehydration, esophagitisDehydration, esophagitis, laparotomy (18%)
Morbidity14-25 d of missed school/year32% completely disabled
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