Patient Education on the Neurogenic Nature of Cyclic Vomiting Syndrome and Future Treatments

Patient Education on the Neurogenic Nature of Cyclic Vomiting Syndrome and Future Treatments

Neurogenic Nature of Cyclic Vomiting SyndromeCyclic vomiting syndrome is the type of condition that utterly baffles patients and their parents, since it typically occurs in children. They’re faced with managing unpredictable spells of extreme vomiting that occur between periods marked by good health. As it turns out, the experts are nearly as perplexed because so little is known about the syndrome’s pathophysiology.

Pharmacists are often on the front line as parents desperately search for OTC treatments that might help their children. You can help them recognize cyclic vomiting syndrome and encourage them to consult a physician. Getting early treatment may help limit future episodes.

Overview of Cyclic Vomiting Syndrome

Cyclic vomiting syndrome (CVS) is estimated to occur in 2 to 3 percent of children. While the median age of onset is about 5 years, it can develop in infants as young as 6 days and has been observed in adults as old as 73 years. In fact, it’s increasingly recognized in adults, where the average age of onset is 21 years and it takes nearly 3 years after the first symptoms to get a diagnosis.1

Everyone knows the misery of vomiting, so just imagine the experience of recurrent, unexplainable vomiting with the following presentation:

  • Intense vomiting – Occurs 6 time per hour on average at its peak.
  • Disabling nausea
  • Dehydration – Often so severe it requires intravenous rehydration.

The following Rome III criteria must be met to diagnose CVS:2

  • Two or more cycles within a 6-month period of intense, unremitting nausea and paroxysmal vomiting that lasts hours to days.
  • At least four episodes of vomiting per hour.
  • Stereotypical stages in each patient.
  • Episodes separated by weeks to months.
  • Symptoms not attributable to any other condition.

Patients may also experience anorexia, abdominal pain, headache and photophobia, which makes it difficult to distinguish CVS from other common conditions such as acute abdomen, migraine, and functional gastrointestinal disorders.

Potential Neurogenic Nature of Cyclic Vomiting Syndrome

For years, CVS has been considered a functional disorder. While its pathophysiology remains unknown, it has been associated with mitochondrial dysfunction. An underlying autonomic neuropathy of the sympathetic nervous system has also been suspected, based on the fact that 90 percent of adults with CVS have impaired vasomotor and sudomotor function. However, an article published in Clinical and Translational Gastroenterology in October 2016 proposes that CVS is a neurogenic disorder driven by multiple endophenotypes.3

The author, David J. Levinthal, MD, PhD from the Division of Gastroenterology, Hepatology and Nutrition at the University of Pittsburgh Medical Center, provides scientific evidence, but also notes that much of it comes from smaller, retrospective studies performed in tertiary care centers using patient-reported data. What follows is a brief summary of his detailed review:

  • CVS patients experience symptoms driven by autonomic, neuroendrocrine, affective, cognitive, and sensorimotor phenomena. For example, it’s common for them to have flushing, an irregular heartbeat, anxiety, insomnia, fatigue, chills, shivering, rapid breathing, abdominal pain, cramps, limb paresthesias, photophobia, and dyspnea.
  • These observations suggest a multi-system disorder with dysfunction in neural circuits that influence each symptom, making CVS a neurogenic disorder.
  • CVS, migraine, epilepsy, and panic disorder share neurological similarities and may be interrelated disorders with common clinical features due to shared endophenotypes and mechanisms dependent on neuronal activity.
  • CVS, migraines, seizures, and panic attacks demonstrate similar characteristic patterns, with flare-ups between phases when the patient feels well. Acute episodes are defined by stereotypical prodromic, attack, and recovery phases.
  • All four disorders are triggered by similar internal and external conditions, such as sensitivity to acute physiological or psychological stressors.
  • Many patients in the four conditions experience symptom onset that’s dependent on a circadian pattern.
  • Exposure to adverse or traumatic life events is associated with increased risk of developing all four conditions.
  • Alteration in basal autonomic activity and provoked autonomic responses have been observed during the inter-episodic phase in all of these conditions.

Implications for Treatment Options

The most significant implication of reframing CVS into a neurogenic disease is that it opens the door to new treatments, as those used for migraines, epilepsy and panic disorder may also be effective for CVS. This would be a major step, as current treatment primarily consists of:

  • Trigger avoidance – Many possible triggers exist and they’re different for each patient. Sleep deprivation, dietary components and psychological stressors, including anxiety over anticipating the next attack, can all induce an acute CVS episode.
  • Prophylactic pharmaceuticals – Cyproheptadine, amitriptyline, phenobarbital, anticonvulsants, erythromycin and propranolol are the mainstay medications used to prevent episodes.
  • Abortive medications – Ondansetron, triptans, promethazine and prochlorperazine have all been used to abort attacks. When single therapy fails, combinations are considered, such as ondansetron plus lorazepam or chlorpromazine with diphenhydramine.

Levinthal’s research suggests that the following may also treat CVS:

  • Small molecule calcitonin gene-related calcitonin gene-related peptide antagonists
  • Glial-neuronal gap junction modulators such as tonabersat
  • Angiotensin II receptor antagonist, Candesartan
  • Atypical neuroleptics such as olanzapine
  • Medications that target the glutamate receptor system
  • Calcium channel blockers, including gabapentin, pregabalin, lamotrigine, and valproate
  • SSRIs and SNRIs

Early Intervention Leads to Fewer CVS Attacks

When pharmacists educate parents and adult patients about CVS, they help ensure early diagnosis and treatment, which makes a big difference—the average duration of CVS episodes drops from 4 days to barely 1 day with early intervention. It also cuts the number of yearly emergency room visits in half. It’s also important to reach out to physicians, especially when parents rely on their pediatrician rather than a gastroenterologist. Professionals who don’t specialize in gastroenterology may not be familiar with CVS, treatment options, or progress being made into the neurogenic nature of CVS.

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Show 3 footnotes

  1. “Cyclic Vomiting Syndrome,” March 2016,
  2. “Cyclic Vomiting Syndrome: A Functional Disorder,” December 2015,
  3. “The Cyclic Vomiting Syndrome Threshold: A Framework for Understanding Pathogenesis and Predicting Successful Treatments,” October 2016,

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