Cyclic vomiting syndrome

Cyclic vomiting syndrome also called abdominal migraine or periodic vomiting, is a functional gastrointestinal disorder (no apparent cause) that causes sudden, repeated attacks—called episodes—of severe nausea, vomiting and tiredness (lethargy) ¹. In some people, there is also severe abdominal pain. Episodes can last from a few hours to several days (1-4 days, most commonly). The episodes are separated by periods without nausea or vomiting (symptom-free periods). The time between episodes can be a few weeks to several months. Episodes can happen regularly or at random. Episodes are similar, meaning that they tend to start at the same time of day, last the same length of time, and occur with the same symptoms and intensity. Episodes can be so severe that you may have to stay in bed for days, unable to go to school or work. You may need treatment at an emergency room or a hospital during episodes. Cyclic vomiting syndrome is diagnosed most often in young children around 3 to 7 years old, but it can affect people of any age. Although more common in children, the number of cyclic vomiting syndrome cases diagnosed in adults is increasing. Cyclic vomiting syndrome can affect you for years or decades. The episodes tend to be similar to each other in symptoms and duration, and are self-limited with return of normal health between episodes.

Cyclic vomiting syndrome is not chronic vomiting that lasts weeks without stopping. Cyclic vomiting syndrome is not a condition that has a definite cause, such as chemotherapy ¹.

Cyclic vomiting syndrome is an unexplained severe vomiting disorder of children and adults that was first described by Dr. S. Gee in 1882. Cyclic vomiting syndrome can begin at any age. It can persist for months, years, or decades. Episodes may recur several times a month or several times a year. Females are affected slightly more than males. The person may be prone to motion sickness, and there is often a family history of migraine. There is a high likelihood that children’s episodes will be replaced by migraine headaches during adolescence.

Cyclic vomiting syndrome is diagnosed most often in young children around 3 to 7 years old, but it can affect people of any age. Although it’s more common in children, the number of cases diagnosed in adults is increasing. The exact prevalence of cyclic vomiting syndrome is unknown; estimates range from 4 to 2,000 per 100,000 children ². Cyclic vomiting syndrome is diagnosed less frequently in adults, although recent studies suggest that the condition may begin in adulthood as commonly as it begins in childhood.

An affected person may vomit several times per hour, potentially leading to a dangerous loss of fluids (dehydration). Additional symptoms can include unusually pale skin (pallor), abdominal pain, diarrhea, headache, fever, and an increased sensitivity to light (photophobia) or to sound (phonophobia). In most affected people, the signs and symptoms of each attack are quite similar. These attacks can be debilitating, making it difficult for an affected person to go to work or school.

Episodes of nausea, vomiting, and lethargy can occur regularly or apparently at random, or can be triggered by a variety of factors. The most common triggers are emotional excitement and infections. Other triggers can include periods without eating (fasting), temperature extremes, lack of sleep, overexertion, allergies, ingesting certain foods or alcohol, and menstruation.

If the condition is not treated, episodes usually occur four to 12 times per year. Between attacks, vomiting is absent, and nausea is either absent or much reduced. However, many affected people experience other symptoms during and between episodes, including pain, lethargy, digestive disorders such as gastroesophageal reflux and irritable bowel syndrome, and fainting spells (syncope). People with cyclic vomiting syndrome are also more likely than people without the disorder to experience depression, anxiety, and panic disorder. It is unclear whether these health conditions are directly related to nausea and vomiting.

Cyclic vomiting syndrome is often considered to be a variant of migraines, which are severe headaches often associated with pain, nausea, vomiting, and extreme sensitivity to light and sound. Cyclic vomiting syndrome is likely the same as or closely related to a condition called abdominal migraine, which is characterized by attacks of stomach pain and cramping. Attacks of nausea, vomiting, or abdominal pain in childhood may be replaced by migraine headaches as an affected person gets older. Many people with cyclic vomiting syndrome or abdominal migraine have a family history of migraines.

Most people with cyclic vomiting syndrome have normal intelligence, although some affected people have developmental delay or intellectual disability. Autism spectrum disorder, which affects communication and social interaction, have also been associated with cyclic vomiting syndrome. Additionally, muscle weakness (myopathy) and seizures are possible. People with any of these additional features are said to have cyclic vomiting syndrome plus.

Cyclic vomiting syndrome is difficult to diagnose because vomiting is a symptom of many disorders. Treatment often involves lifestyle changes to help prevent the events that can trigger vomiting episodes. Medications, including anti-nausea and migraine therapies, may help lessen symptoms.

The symptoms of cyclic vomiting syndrome often begin in the morning. Signs and symptoms include:

• Severe vomiting that occurs several times an hour, continues for hours to days, but lasts less than one week
• Three or more separate episodes of vomiting with no apparent cause in the past six months, or five or more episodes occurring at any time
• Retching—trying to vomit but having nothing come out of your mouth, also called dry vomiting
• Severe nausea
• Intense sweating

Other symptoms of cyclic vomiting syndrome may include one or more of the following:

• Abdominal pain
• Abnormal drowsiness
• Lack of appetite
• Diarrhea
• Fever
• Dizziness
• Sensitivity to light or sound
• Headaches
• Retching or gagging
• Not wanting to talk
• Drooling or spitting
• Extreme thirst
• Pale skin

The time between vomiting episodes is usually symptom-free.

People with cyclic vomiting syndrome may have other health problems, including ³:

• migraines
• anxiety and depression
• gastroparesis
• autonomic nervous system disorders
• high blood pressure
• gastroesophageal reflux disease (GERD)
• irritable bowel syndrome (IBS)

You may be more likely to get cyclic vomiting syndrome if you have:

• migraines or a family history of migraines
• a history of long-term marijuana use
• a tendency to get motion sickness

Among adults with cyclic vomiting syndrome, about 6 out of 10 are Caucasian ³.

The exact prevalence of cyclic vomiting syndrome is unknown; estimates range from 4 to 2,000 per 100,000 children. Doctors diagnose about 3 out of 100,000 children with cyclic vomiting syndrome every year ⁴. Experts don’t know how common cyclic vomiting syndrome is in adults. Cyclic vomiting syndrome is diagnosed less frequently in adults, although recent studies suggest that the condition may begin in adulthood as commonly as it begins in childhood.

There’s no cure for cyclic vomiting syndrome, though many children no longer have vomiting episodes by the time they reach adulthood. For those experiencing cyclic vomiting episode, treatment focuses on controlling the signs and symptoms. You or your child may be prescribed:

• Anti-nausea drugs
• Pain-relieving medications
• Medications that suppress stomach acid
• Antidepressants
• Anti-seizure medications

The same types of medications used for migraines can sometimes help stop or even prevent episodes of cyclic vomiting. These medications may be recommended for people whose episodes are frequent and long lasting, or for people with a family history of migraine.

IV fluids may need to be given to prevent dehydration. Treatment is individualized based on the severity and duration of symptoms as well as the presence of complications.

Coping and support

Because you never know when the next episode might occur, cyclic vomiting syndrome can be difficult for the whole family. Children may be especially concerned, and may worry constantly that they’ll be with other children when an episode happens.

You or your child may benefit from connecting with others who understand what it’s like to live with the uncertainty of cyclic vomiting syndrome. Ask your doctor about support groups in your area.

What are the phases of cyclic vomiting syndrome?

Cyclic vomiting syndrome has four phases:

1. Prodrome phase
2. Vomiting phase
3. Recovery phase
4. Well phase

The symptoms will vary as you go through the four phases of cyclic vomiting syndrome:

• Prodrome phase. During the prodrome phase, you feel an episode coming on. Often marked by intense sweating and nausea—with or without pain in your abdomen—this phase can last from a few minutes to several hours. Your skin may look unusually pale.
• Vomiting phase. The main symptoms of this phase are severe nausea, vomiting, and retching. At the peak of this phase, you may vomit several times an hour. You may be:
  • quiet and able to respond to people around you
  • unable to move and unable to respond to people around you
  • twisting and moaning with intense pain in your abdomen

Nausea and vomiting can last from a few hours to several days.

• Recovery phase. Recovery begins when you stop vomiting and retching and you feel less nauseated. You may feel better gradually or quickly. The recovery phase ends when your nausea stops and your healthy skin color, appetite, and energy return.
• Well phase. The well phase happens between episodes. You have no symptoms during this phase.

What may trigger an episode of cyclic vomiting?

Triggers for an episode of cyclic vomiting may include:

• emotional stress
• anxiety or panic attacks, especially in adults
• infections, such as colds, flu, or chronic sinusitis
• intense excitement before events such as birthdays, holidays, vacations, and school outings, especially in children
• lack of sleep
• physical exhaustion
• allergies
• temperature extremes of hot or cold
• drinking alcohol
• menstrual periods
• motion sickness
• periods without eating (fasting)

Eating certain foods, such as chocolate, cheese, and foods with monosodium glutamate (MSG) may play a role in triggering episodes.

Cyclic vomiting syndrome complications

The severe vomiting and retching that happen during cyclic vomiting episodes may cause the following complications:

• Dehydration. Excessive vomiting causes the body to lose water quickly. Severe cases of dehydration may need to be treated in the hospital.
• Injury to the food tube. The stomach acid that comes up with the vomit can damage the tube that connects the mouth and stomach (esophagus). Sometimes the esophagus becomes so irritated it bleeds.
• Esophagitis
• Mallory-Weiss tears
• Tooth decay. The acid in vomit can corrode tooth enamel.

A study that evaluated the relationship between anxiety and health-related quality of life in children and adolescents with cyclic vomiting syndrome reported that children and adolescents with cyclic vomiting syndrome 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 cyclic vomiting syndrome. Assessment and treatment of anxiety in children and adolescents with cyclic vomiting syndrome may have a positive impact on health-related quality of life ⁵.

Phases of cyclic vomiting syndrome

Cyclic vomiting syndrome has four phases:

1. Prodrome phase
2. Vomiting phase
3. Recovery phase
4. Well phase

The symptoms will vary as you go through the four phases of cyclic vomiting syndrome:

• Prodrome phase. During the prodrome phase, you feel an episode coming on. Often marked by intense sweating and nausea—with or without pain in your abdomen—this phase can last from a few minutes to several hours. Your skin may look unusually pale.
• Vomiting phase. The main symptoms of this phase are severe nausea, vomiting, and retching. At the peak of this phase, you may vomit several times an hour. You may be:
  • quiet and able to respond to people around you
    • unable to move and unable to respond to people around you
• twisting and moaning with intense pain in your abdomen

Nausea and vomiting can last from a few hours to several days.

• Recovery phase. Recovery begins when you stop vomiting and retching and you feel less nauseated. You may feel better gradually or quickly. The recovery phase ends when your nausea stops and your healthy skin color, appetite, and energy return.
• Well phase. The well phase happens between episodes. You have no symptoms during this phase.

Cyclic vomiting syndrome signs and symptoms

The main symptoms of cyclic vomiting syndrome are sudden, repeated attacks—called episodes—of severe nausea and vomiting. Symptoms include vomiting episodes that recur in a cyclical pattern (for example every two weeks or once a month). The vomiting episodes start suddenly, typically with nausea, and progresses to vomiting later. The episodes can sometimes wake the affected person from sleep. You may vomit several times an hour. Episodes can last from a few hours to several days. Episodes may make you feel very tired and drowsy.

Episodes may begin at any time, but often start during the early morning hours. There is relentless nausea with repeated bouts of vomiting or retching. The person is pale, listless, and resists talking. They often drool or spit and have an extreme thirst. They may experience intense abdominal pain and less often headache, low-grade fever, and diarrhea. Prolonged vomiting may cause mild bleeding from irritation of the esophagus. The symptoms are frightening to the person and family, and can be life-threatening if delayed treatment leads to severe dehydration.

The episodes are “stereotypical” which means that each episode resembles previous episodes. Other symptoms can include stomach pain, diarrhea and headache. The vomiting “attacks” can become so severe that patients become dehydrated and require medical attention in the emergency room.

In between episodes, patients feel completely well. Once an episode resolves, affected children often feel normal within hours.

Many children with cyclic vomiting syndrome also have a diagnosis of migraines or a family history of migraines.

The symptoms of cyclic vomiting syndrome often begin in the morning. Signs and symptoms include:

• Three or more recurrent episodes of vomiting that start around the same time and last for a similar length of time
• Varying intervals of generally normal health without nausea between episodes
• Intense nausea and sweating before an episode starts.

Pattern or cycle of symptoms in children

A doctor will often suspect cyclic vomiting syndrome in a child when all of the following are present ⁶:

• at least five episodes over any time period, or a minimum of three episodes over a 6-month period
• episodes lasting 1 hour to 10 days and happening at least 1 week apart
• episodes similar to previous ones, tending to start at the same time of day, lasting the same length of time, and happening with the same symptoms and intensity
• vomiting during episodes happening at least four times an hour for at least 1 hour
• episodes are separated by weeks to months, usually with no symptoms between episodes
• after appropriate medical evaluation, symptoms cannot be attributed to another medical condition

Pattern or cycle of symptoms in adults

A doctor will often suspect cyclic vomiting syndrome in adults when all of the following are present ⁷:

• three or more separate episodes in the past year and two episodes in the past 6 months, happening at least 1 week apart
• episodes that are usually similar to previous ones, meaning that episodes tend to start at the same time of day and last the same length of time—less than 1 week
• no nausea or vomiting between episodes, but other, milder symptoms can be present between episodes
• no metabolic, gastrointestinal, central nervous system, structural, or biochemical disorders

A personal or family history of migraines supports the doctor’s diagnosis of cyclic vomiting syndrome.

Other signs and symptoms during a vomiting episode may include:

• Abdominal pain
• Diarrhea
• Dizziness
• Sensitivity to light
• Headache
• Retching or gagging.

Your doctor may diagnose cyclic vomiting syndrome even if your pattern of symptoms or your child’s pattern of symptoms do not fit the patterns described here. Talk to your doctor if your symptoms or your child’s symptoms are like the symptoms of cyclic vomiting syndrome.

Cyclic vomiting syndrome causes

Experts aren’t sure what causes cyclic vomiting syndrome. Although the causes of cyclic vomiting syndrome have yet to be determined, researchers have proposed several factors that may contribute to cyclic vomiting syndrome. Some possible causes include genes, changes in brain function, hormone imbalances and gastrointestinal problems. Many researchers believe that cyclic vomiting syndrome is a migraine-like condition ⁸, which suggests that it is related to changes in signaling between nerve cells (neurons) in certain areas of the brain. In one study, patients with cyclic vomiting syndrome have a significantly higher prevalence of family members with migraine headaches (82% vs 14% of control subjects with a chronic vomiting pattern) ⁹. Furthermore, 28% of patients with cyclic vomiting syndrome whose vomiting subsequently resolved developed migraine headaches. Approximately 80% of affected patients with family histories positive for migraine respond to antimigraine therapy ⁹.

Many affected individuals have abnormalities of the autonomic nervous system, which controls involuntary body functions such as heart rate, blood pressure, and digestion. Based on these abnormalities, cyclic vomiting syndrome is often classified as a type of dysautonomia ¹⁰.

Some conditions experts believe may play a role in cyclic vomiting syndrome:

• problems with nerve signals between the brain and digestive tract
• problems with the way the brain and endocrine system react to stress
• mutations in certain genes that are associated with an increased chance of getting cyclic vomiting syndrome

Some cases of cyclic vomiting syndrome, particularly those that begin in childhood, may be related to changes in mitochondrial DNA ¹¹. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA known as mitochondrial DNA or mtDNA.

Several changes in mitochondrial DNA have been associated with cyclic vomiting syndrome. Some of these changes alter single DNA building blocks (nucleotides), whereas others rearrange larger segments of mitochondrial DNA. These changes likely impair the ability of mitochondria to produce energy. Researchers speculate that the impaired mitochondria may cause certain cells of the autonomic nervous system to malfunction, which could affect the digestive system. However, it remains unclear how changes in mitochondrial function could cause episodes of nausea, vomiting, and lethargy; abdominal pain; or migraines in people with cyclic vomiting syndrome.

In most cases of cyclic vomiting syndrome, affected people have no known history of the disorder in their family. However, many affected individuals have a family history of related conditions, such as migraines, irritable bowel syndrome, or depression, in their mothers and other maternal relatives. This family history suggests an inheritance pattern known as maternal inheritance or mitochondrial inheritance, which applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.

Occasionally, people with cyclic vomiting syndrome have a family history of the disorder that does not follow maternal inheritance. In these cases, the inheritance pattern is unknown.

Specific bouts of vomiting may be triggered by:

• Colds, allergies or sinus problems
• Emotional stress or excitement, especially in children
• Anxiety or panic attacks, especially in adults
• Certain foods and drinks, such as alcohol, caffeine, chocolate or cheese
• Overeating, eating right before going to bed or fasting
• Hot weather
• Physical exhaustion
• Exercising too much
• Menstruation
• Motion sickness

Identifying the triggers for vomiting episodes may help with managing cyclic vomiting syndrome.

What may trigger an episode of cyclic vomiting?

Triggers for an episode of cyclic vomiting may include:

• Emotional stress or excitement, especially in children
• Anxiety or panic attacks , especially in adults
• Infections, such as colds, flu, or chronic sinusitis
• Intense excitement before events such as birthdays, holidays, vacations, and school outings, especially in children
• Lack of sleep
• Physical exhaustion
• Allergies
• Temperature extremes of hot or cold
• Drinking alcohol
• Menstruation or menstrual periods
• Motion sickness
• Periods without eating (fasting)
• Foods, such as caffeine, chocolate or cheese
• Overeating, eating right before going to bed or fasting
• Hot weather
• Physical exhaustion
• Exercising too much

Eating certain foods, such as chocolate, cheese, and foods with monosodium glutamate (MSG) may play a role in triggering episodes.

Identifying the triggers for vomiting episodes may help with managing cyclic vomiting syndrome.

Cyclic vomiting syndrome inheritance pattern

In most cases of cyclic vomiting syndrome, affected people have no known history of the disorder in their family. However, many affected individuals have a family history of related conditions, such as migraines, irritable bowel syndrome, or depression, in their mothers and other maternal relatives. This family history suggests an inheritance pattern known as maternal inheritance or mitochondrial inheritance, which applies to genes contained in mitochondrial DNA (mtDNA). Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children.

Occasionally, people with cyclic vomiting syndrome have a family history of the disorder that does not follow maternal inheritance. In these cases, the inheritance pattern is unknown.

Risk factors for developing cyclic vomiting syndrome

The relationship between migraines and cyclic vomiting syndrome isn’t clear. But many children with cyclic vomiting syndrome have a family history of migraines or have migraines themselves when they get older. In adults, the association between cyclic vomiting syndrome and migraine may be lower.

Chronic use of marijuana (Cannabis sativa) also has been associated with cyclic vomiting syndrome because some people use marijuana to relieve their nausea. However, chronic marijuana use can lead to a condition called cannabis hyperemesis syndrome, which typically leads to persistent vomiting without normal intervening periods. People with this syndrome often demonstrate frequent showering or bathing behavior.

Cannabis hyperemesis syndrome can be confused with cyclic vomiting syndrome. To rule out cannabis hyperemesis syndrome, you need to stop using marijuana for at least one to two weeks to see if vomiting lessens. If it doesn’t, your doctor will continue testing for cyclic vomiting syndrome.

Cyclic vomiting syndrome prevention

Many people know what triggers their cyclic vomiting episodes. Avoiding those triggers can reduce the frequency of episodes. While you may feel well between episodes, it’s very important to take medications as prescribed by your doctor.

If episodes occur more than once a month or require hospitalization, your doctor may recommend preventive medicine, such as amitriptyline, propranolol (Inderal), cyproheptadine and topiramate.

Lifestyle changes also may help, including:

• Getting adequate sleep
• Downplaying the importance of upcoming events because excitement can be a trigger
• Avoiding trigger foods, such as caffeine, cheese and chocolate
• Eating small meals and small carbohydrate-containing snacks daily at regular times.

Cyclic vomiting syndrome differential diagnosis

Other causes of recurrent vomiting include:

• Gastroesophageal reflux disease (GERD)
• Stomach inflammation (gastritis)
• Pancreas inflammation (pancreatitis)
• Food allergies
• Kidney/urologic abnormalities (ureteropelvic junction obstruction)
• Stomach infections
• Cannabis abuse
• Brain tumors or other lesions in the head
• Metabolic disease

Cyclic vomiting syndrome diagnosis

Cyclic vomiting syndrome can be difficult to diagnose. There’s no specific test to confirm the diagnosis, and vomiting is a sign of many conditions such as gastroenteritis or food poisoning that must be ruled out first.

Doctors diagnose cyclic vomiting syndrome based on family and medical history, a physical exam, pattern of symptoms, and medical tests. Your doctor may perform medical tests to rule out other diseases and conditions that may cause nausea and vomiting.

Family and medical history

Your doctor will ask about your family and medical history. He or she may ask for details about your history of health problems such as migraines, irritable bowel syndrome (IBS) and gastroparesis. Your doctor may also ask about your history of mental health problems, use of substances such as marijuana, and cigarette smoking.

Physical exam

During a physical exam, your doctor will:

• examine your body
• check your abdomen for unusual sounds, tenderness, or pain
• check your nerves, muscle strength, reflexes, and balance

Pattern or cycle of symptoms in children

A doctor will often suspect cyclic vomiting syndrome in a child when all of the following are present ⁶:

• at least five episodes over any time period, or a minimum of three episodes over a 6-month period
• episodes lasting 1 hour to 10 days and happening at least 1 week apart
• episodes similar to previous ones, tending to start at the same time of day, lasting the same length of time, and happening with the same symptoms and intensity
• vomiting during episodes happening at least four times an hour for at least 1 hour
• episodes are separated by weeks to months, usually with no symptoms between episodes
• after appropriate medical evaluation, symptoms cannot be attributed to another medical condition

Pattern or cycle of symptoms in adults

A doctor will often suspect cyclic vomiting syndrome in adults when all of the following are present ⁷:

• three or more separate episodes in the past year and two episodes in the past 6 months, happening at least 1 week apart
• episodes that are usually similar to previous ones, meaning that episodes tend to start at the same time of day and last the same length of time—less than 1 week
• no nausea or vomiting between episodes, but other, milder symptoms can be present between episodes
• no metabolic , gastrointestinal , central nervous system , structural, or biochemical disorders

A personal or family history of migraines supports the doctor’s diagnosis of cyclic vomiting syndrome.

Your doctor may diagnose cyclic vomiting syndrome even if your pattern of symptoms or your child’s pattern of symptoms do not fit the patterns described here. Talk to your doctor if your symptoms or your child’s symptoms are like the symptoms of cyclic vomiting syndrome.

Medical tests

Doctors use lab tests, upper GI (gastrointestinal) endoscopy, and imaging tests to rule out other diseases and conditions that cause nausea and vomiting. Once other diseases and conditions have been ruled out, a doctor will diagnose cyclic vomiting syndrome based on the pattern or cycle of symptoms.

Lab tests

Your doctor may use the following lab tests:

• Blood tests can show signs of anemia, dehydration, inflammation, infection, and liver problems.
• Urine tests can show signs of dehydration, infection, and kidney problems.
• Motility tests to monitor the movement of food through the digestive system and to check for digestive disorders

Blood and urine tests can also show signs of mitochondrial diseases.

Upper GI endoscopy

Your doctor may perform an upper GI endoscopy to look for problems in your upper digestive tract that may be causing nausea and vomiting.

A test that uses a small, flexible tube with a light and a camera lens at the end (endoscope) to examine the inside your upper digestive tract. Tissue samples from inside may also be taken for examination and testing.

Imaging tests

A doctor may perform one of more of the following imaging tests:

• Ultrasound of the abdomen. A diagnostic imaging technique which creates images from the rebound of high-frequency sound waves in the internal organs. Used to evaluate potential diseases in the kidneys or gallbladder.
• Gastric emptying test, also called gastric emptying scintigraphy. This test involves eating a bland meal, such as eggs or an egg substitute, that contains a small amount of radioactive material. An external camera scans the abdomen to show where the radioactive material is located. A radiologist can then measure how quickly the stomach empties after the meal. Health care professionals perform gastric emptying tests only between episodes.
• Upper GI series. A patient swallows a contrast agent and a series of X-rays are performed to evaluate the esophagus, stomach, and a portion of the small intestine. Used to evaluate for an abnormal twisting of the intestine called a malrotation.
• MRI scan or CT scan of the brain. Magnetic resonance imaging (MRI) is an imaging procedure that uses a powerful magnet, radiofrequencies, and a computer to produce detailed images of the brain. This is to exclude possible neurologic causes of vomiting.

Cyclic vomiting syndrome treatment

There’s no cure for cyclic vomiting syndrome, though many children no longer have vomiting episodes by the time they reach adulthood. For those experiencing a cyclic vomiting episode, treatment focuses on identifying and avoiding triggering factors, controlling the signs and symptoms. You or your child may be prescribed ¹²:

• Anti-nausea drugs
• Pain-relieving medications
• Medications that suppress stomach acid
• Antidepressants
• Anti-seizure medications

The same types of medications used for migraines can sometimes help stop or even prevent episodes of cyclic vomiting. These medications may be recommended for people whose episodes are frequent and long lasting, or for people with a family history of migraine.

IV fluids may need to be given to prevent dehydration. Treatment is individualized based on the severity and duration of symptoms as well as the presence of complications.

Although several classes of medications are utilized for long-term management of cyclic vomiting syndrome, remission of symptoms is not achievable in every patient. The main risk factors for non-response include coexisting poorly controlled migraine headaches, psychiatric disorders, and chronic opioid or marijuana use ¹³. In addition, medications used for cyclic vomiting syndrome prophylaxis carry the potential for undesirable adverse effects or complications. Table 1 provides the summary of literature regarding cyclic vomiting syndrome treatment.

Table 1. Summary of evidence for cyclic vomiting syndrome treatment

Treatment	Medication and doses
Abortive treatment
IV hydration with dextrose and potassium	10% dextrose with 0.45%–0.9% normal saline
5-HT3 receptor antagonists (eg, ondansetron)	Ondansetron
	Doses not provided
Antiemetic	Promethazine or diphenhydramine Doses not provided
Benzodiazepines	Lorazepam intravenous 1–2 mg every 3 hours
IV opioids	N/A
IV ketorolac	N/A
5-HT1B,1Dagonist	Sumatriptan 6 mg subcutaneous injection (adult), or 20 mg nasal spray, or Age-based dosing[(age x4+20)/100×3 mg]
NK1 receptor antagonists	Aprepitant 125 mg orally initially, followed if required by 80 mg on day 2 and 3 in children >20 kg, 80 mg for 3 consecutive days for those weighing between 15 and 20 kg, at 80 mg at day 1 and 40 mg on day 2 and 3 for those children <15 kg
Preventive (prophylaxis) treatment
Tricyclic antidepressants	Amitriptyline (children >5 years old)
	Starting dose: 0.25–0.5 mg/kg per day at bedtime (titrate weekly by 5–10mg)
	Target dose: 1–1.5 mg/kg per day at bedtime
	Amitriptyline (adult)
	Starting dose: 10–50 mg daily
	Target dose: 1 mg/kg/day or titrated to effect
	Nortriptyline (adult)
	Starting dose: 10–25 mg daily
	Target dose: titrated to effect
	Doxepin (adult)
	Starting dose: 10–25 mg daily
	Target dose: titrated to effect
Antiepileptic	Topiramate (pediatric)
	Starting dose: 25 mg daily
	Effective dose range: 25–75 mg/day
	Valproate (pediatric) Starting dose: 10 mg/kg/day (in 2 divided doses) Effective dose range: 20–40 mg/kg/day Phenobarbital (pediatric) Starting dose: ~2 mg/kg/day (median: 60 mg) Effective dose range: 30–120 mg/day Zonisamide (adult) Starting dose: 100 mg daily Effective dose range: 100–700 mg/day (median: 400 mg) Levetiracetam (adult) Starting dose: 500 mg daily Effective dose range: 500–3000 mg/day (median:1000 mg)
Antimigraine	Propranol
	Starting dose: 1 mg/kg/day
	Target dose: titrated to effect
Histamine H1 antagonist	Cyproheptadine Various doses used
NK1 receptor antagonists	Aprepitant 40 mg orally twice/week in children <40 kg, 80 mg in children 40–60 kg, and 125 mg in children >60 kg
Dietary supplement	l-carnitine
	Coenzyme Q10 200 mg twice daily

[Source ¹²]

How doctors treat cyclic vomiting syndrome depends on the phase. Your doctor may:

• prescribe medicines
• treat health problems that may trigger the disorder
• recommend
• staying away from triggers
• ways to manage triggers
• getting plenty of sleep and rest

Prodrome phase

Acute phase treatment goals of cyclic vomiting syndrome symptoms include preventing dehydration and terminating nausea, vomiting, and abdominal pain ¹⁴. Dextrose, saline, and potassium replacement is used for hydration.1,6 Abortive intravenous antiemetic agents, especially 5-HT3 (serotonin type 3) receptor antagonists (e.g, ondansetron), are generally effective. Other anti-emetic agents such as promethazine and diphenhydramine are also considered effective ¹⁴. Benzodiazepines (eg, lorazepam 1–2 mg intravenously every 3 hours) can be considered for admitted patients requiring deep sedation or sleep induction. Intravenous opioids or ketorolac may be initially warranted to treat severe abdominal pain in the acute setting. Antimigraine serotonin 5-HT1B, 1D agonists (e.g, sumatriptan) have provided anecdotal success in children with personal or family histories of migraines, and therefore, can also be considered in adults with the presence of such histories ⁷.

Taking medicines early in prodrome phase can sometimes help stop an episode from happening. Your doctor may recommend over-the-counter medicines or prescribe medicines such as:

• ondansetron (Zofran) or promethazine (Phenergan) for nausea
• sumatriptan (Imitrex) for migraines
• lorazepam (Ativan) for anxiety
• ibuprofen for pain

Your doctor may recommend over-the-counter medicines to reduce the amount of acid your stomach makes, such as:

• famotidine (Pepcid)
• ranitidine (Zantac)
• omeprazole (Prilosec)
• esomeprazole (Nexium)

Vomiting phase

During vomiting phase, you should stay in bed and sleep in a dark, quiet room. You may have to go to a hospital if your nausea and vomiting are severe or if you become severely dehydrated. Your doctor may recommend or prescribe the following for children and adults:

• medicines for:
  • nausea
  • migraines
  • anxiety
  • pain
• medicines that reduce the amount of acid your stomach makes

When the vomiting phase has stopped, it’s very important to drink fluids, such as an oral electrolyte solution (Pedialyte) or a sports drink (Gatorade, Powerade, others) diluted with 1 ounce of water for every ounce of sports drink. Some people may feel well enough to begin eating a normal diet soon after they stop vomiting. But if you don’t or your child doesn’t feel like eating right away, you might start with clear liquids and then gradually add solid food.

If vomiting episodes are triggered by stress or excitement, try during a symptom-free interval to find ways to reduce stress and stay calm. Eating small meals and small carbohydrate-containing snacks daily, instead of three large meals, also may help.

If you go to a hospital, your doctor may treat you with:

• intravenous (IV) fluids for dehydration
• medicines for symptoms
• IV nutrition if an episode continues for several days.

During the recovery phase, you may need IV fluids for a while. Your doctor may recommend that you drink plenty of water and liquids that contain glucose and electrolytes, such as

• broths
• caffeine-free soft drinks
• fruit juices
• sports drinks
• oral rehydration solutions, such as Pedialyte

If you’ve lost your appetite, start drinking clear liquids and then move slowly to other liquids and solid foods. Your doctor may prescribe medicines to help prevent future episodes.

Remission phase

The goal of therapy for remission phase (well phase) is prophylaxis (prevention) of further episodes ¹⁵. During the well phase, your doctor may prescribe medicines to help prevent episodes and how often and how severe they are, such as:

• amitriptyline (Elavil)
• cyproheptadine (Periactin)
• propranolol (Inderal)
• topiramate (Topamax)
• zonisamide (Zonegran)

Your doctor may also recommend coenzyme Q10, levocarnitine (L-carnitine), or riboflavin as dietary supplements to help prevent episodes.

Antidepressant, antiepileptic, and anti-migraine pharmacotherapies show an overall reduction or remission of cyclic vomiting syndrome symptoms in more than 70% of patients ¹⁶.

Refractory patients

Second-line approaches to cyclic vomiting syndrome treatment typically target specific comorbid symptoms or conditions. Agents include benzodiazepines (e.g, lorazepam) in anxiety disorders, antispasmodics (e.g, dicyclomine) for irritable bowel syndrome-like abdominal pain, proton pump inhibitors for esophagitis secondary to repeated vomiting, antiemetic agents (e.g, ondansetron, promethazine, or prochlorperazine) for refractory nausea, and analgesics (e.g, tramadol, ketorolac, and infrequently limited opioids) for abdominal pain management ¹⁷.

A novel approach to treating cyclic vomiting syndrome is the use of neurokinin (NK1) receptor antagonists. Aprepitant was the first NK1 receptor antagonist approved for prevention of chemotherapy induced nausea and vomiting. Aprepitant appears to also have antidepressant and anxiolytic effects. A recent trial in 41 pediatric patients, refractory to conventional cyclic vomiting syndrome therapies were treated acutely or prophylactically with aprepitant ¹⁸. The prophylactic dose of aprepitant 40 mg orally twice/week in children <40 kg, 80 mg in children 40–60 kg, and 125 mg in children >60 kg. An acute regimen of aprepitant was given at 125 mg orally at the beginning of prodromal phase at least 30 minutes before the acute phase when all the patients were able to swallow the capsule, followed if required by 80 mg on day 2 and 3 in children >20 kg, 80 mg for 3 consecutive days for those weighing between 15 and 20 kg, at 80 mg at day, 1 and 40 mg on day 2 and 3 for those children <15 kg. At 12 months on intention-to-treat analysis, 13 children (81%) taking aprepitant prophylactically achieved either complete (3/16, 19%) or partial (10/16, 62%) clinical response. Of those taking aprepitant acutely, 19 children (76%) had either complete (3/25, 12%) or partial (16/25, 64%). Adverse effects included hiccups (19%), fatigue (12.5%), increased appetite (12.5%), mild headache (6%), and severe migraine (6%) ¹⁸.

Other second-line therapies for nonresponders include medications that improve mitochondrial function (e.g, l-carnitine or coenzyme Q10). Coenzyme Q10 and l-carnitine use is based on the hypothesis that cyclic vomiting syndrome is result of mitochondrial dysfunction which leads to an energy imbalance.

• Coenzyme Q10 (ubiquinone), is a natural substance made in the body that is available as a supplement. Coenzyme Q10 assists with the basic functions of cells.
• L-carnitine, is a natural substance that is made in the body and is available as a supplement. L-carnitine helps your body turn fat into energy.

Coenzyme Q10 was found to be effective in 68% of cyclic vomiting syndrome patients ¹⁹. Several case series have found L-carnitine effective ²⁰.

L-carnitine and coenzyme Q10 may work by helping your body overcome difficulty in converting food into energy (mitochondrial dysfunction). Some researchers believe mitochondrial dysfunction may be a factor causing both cyclic vomiting syndrome and migraine.

Be sure to see a doctor and have the diagnosis of cyclic vomiting syndrome confirmed before starting any supplements. Always check with your doctor before taking any supplements to be sure you or your child is taking a safe dose and that the supplement won’t adversely interact with any medications you’re taking. Some people may experience side effects from L-carnitine and coenzyme Q10 that are similar to the symptoms of cyclic vomiting syndrome, including nausea, diarrhea and loss of appetite.

Other therapies demonstrating successful cyclic vomiting syndrome treatment in case reports and case series include chlorpromazine ²¹, gonadotropin releasing hormone analogue ²², mirtazapine ²³, onabotulinumtoxinA ²⁴, and risperidone ²⁵.

Medical treatment

• Prophylactic therapy (daily medication to prevent episodes). 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 the following:
  • Cyproheptadine
  • Amitriptyline
  • Anticonvulsants such as topiramate, zonisamide, and levetiracetam
  • Propranolol
  • Phenobarbital
  • Erythromycin
• Abortive therapies (therapies that stop the episode once it starts). Medications used for aborting episodes include the following:
  • Ondansetron
  • Promethazine
  • Prochlorperazine
  • Triptans
• Anti-nausea medications
• Anti-anxiety medications
• Anti-migraine treatments

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 ²⁶. 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) ²⁷. Most of these drugs are non-gastrointestinal 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 ²⁸.

The guidelines formulated by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition 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 ²⁸.

Although no randomized control trials have examined medications used in cyclic vomiting syndrome, several open-label trials and retrospective studies support the use of amitriptyline as first-line therapy in patients with cyclic vomiting syndrome who are older than 5 years. In an open-label study of 41 patients with cyclic vomiting syndrome 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 ²⁹.

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 ²⁹. 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 emergency department visits and hospitalizations decreased from 15 to 3.3 over 2 years.

In a study of 132 patients with cyclic vomiting syndrome who had been monitored for 4 years, 17 subjects were identified as nonresponders to tricyclic antidepressant therapy ³⁰. 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 cyclic vomiting syndrome 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 cyclic vomiting syndrome or their parents to assess the efficacy of coenzyme Q10 and amitriptyline ³¹. 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 ³¹. 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 ³². 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 cyclic vomiting syndrome 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 ³³. Newer antiepileptic agents appeared beneficial as maintenance medications for nearly three fourths of adults with cyclic vomiting syndrome.

In a retrospective study of 101 adults with cyclic vomiting syndrome, most patients (86%) responded to treatment with tricyclic antidepressants (TCAs), anticonvulsants (topiramate), coenzyme Q10, and L-carnitine ³⁴. 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 ³⁵.

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 ³⁶.

Ondansetron, a 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 the use of a benzodiazepine or diphenhydramine as an adjunctive antinausea agent ⁹. 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 cyclic vomiting syndrome ³⁵.

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% ³⁵. 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 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 ³⁷.

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 ³⁸. 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 ³⁵. The combination of lorazepam and ondansetron appears to be more effective than ondansetron alone.

Psychological treatment

Some patients may have cyclic vomiting episodes triggered by psychological stress — these can be negative stressors (such as taking a test) or positive (such as vacation or holidays). Additionally, cyclic vomiting syndrome is a stressful illness. Therefore, many patients benefit from counseling to promote relaxation.

Avoidance of triggers

In some cases of cyclic vomiting syndrome, avoiding identified dietary triggers such as chocolate, cheese, and monosodium glutamate (MSG) can prevent episodes without the use of medication ²⁸. 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 cyclic vomiting syndrome 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 ³⁹.

Cyclic vomiting syndrome diet

Your diet will not help prevent or relieve cyclic vomiting syndrome episodes but will help you recover and keep you healthy.

Your doctor may recommend coenzyme Q10, levocarnitine (L-carnitine), or riboflavin as dietary supplements to help prevent episodes.

What should I eat and drink?

When your nausea and vomiting stop, you can generally go back to your regular diet right away. In some cases, you may want to start with clear liquids and go slowly back to your regular diet. You should eat well-balanced and nutritious meals between your episodes. Your doctors will recommend that you not skip meals in between episodes. If you are dehydrated, drink plenty of liquids that contain glucose and electrolytes, such as:

• broths
• caffeine-free soft drinks
• fruit juices
• sports drinks
• oral rehydration solutions, such as Pedialyte

What should I avoid eating?

In between episodes, you should avoid eating foods that may have triggered past episodes. Eating certain foods such as chocolate, cheese, and foods with monosodium glutamate (MSG), may trigger an episode in some people. Adults should avoid drinking alcohol.

Lifestyle and home remedies

Lifestyle changes can help control the signs and symptoms of cyclic vomiting syndrome. People with cyclic vomiting syndrome generally need to get adequate sleep. Once vomiting begins, it may help to stay in bed and sleep in a dark, quiet room.

When the vomiting phase has stopped, it’s very important to drink fluids, such as an oral electrolyte solution (Pedialyte) or a sports drink (Gatorade, Powerade, others) diluted with 1 ounce of water for every ounce of sports drink.

Some people may feel well enough to begin eating a normal diet soon after they stop vomiting. But if you don’t or your child doesn’t feel like eating right away, you might start with clear liquids and then gradually add solid food.

If vomiting episodes are triggered by stress or excitement, try during a symptom-free interval to find ways to reduce stress and stay calm. Eating small meals and low-fat snacks daily, instead of three large meals, also may help.

Alternative medicine

Alternative and complementary treatments may help prevent vomiting episodes, although none of these treatments has been well-studied. These treatments include:

• Coenzyme Q10 (ubiquinone), a natural substance made in the body that is available as a supplement. Coenzyme Q10 assists with the basic functions of cells.
• L-carnitine, a natural substance that is made in the body and is available as a supplement. L-carnitine helps your body turn fat into energy.
• Riboflavin (vitamin B-2), a vitamin found in certain foods and available as a supplement. Riboflavin plays a role in the body’s mitochondrial processes.

Coenzyme Q10, L-carnitine and riboflavin may work by helping your body overcome difficulty in converting food into energy (mitochondrial dysfunction). Some researchers believe mitochondrial dysfunction may be a factor causing both cyclic vomiting syndrome and migraine.

Be sure to see a doctor and have the diagnosis of cyclic vomiting syndrome confirmed before starting any supplements. Always check with your doctor before taking any supplements to be sure you or your child is taking a safe dose and that the supplement won’t adversely interact with any medications you’re taking. Some people may experience side effects from coenzyme Q10, L-carnitine and riboflavin that are similar to the symptoms of cyclic vomiting syndrome, including nausea, diarrhea and loss of appetite.

Coping and support

Because you never know when the next episode might occur, cyclic vomiting syndrome can be difficult for the whole family. Children may be especially concerned, and may worry constantly that they’ll be with other children when an episode happens.

You or your child may benefit from connecting with others who understand what it’s like to live with the uncertainty of cyclic vomiting syndrome. Families are encouraged to contact the Cyclic Vomiting Syndrome Association (http://cvsaonline.org), which is an international voluntary organization that serves the needs of cyclic vomiting syndrome patients in the United States and Canada, for ongoing support and information. Ask your doctor about support groups in your area.

Cyclic vomiting syndrome prognosis

Once patients are properly diagnosed and treated, most improve. Additionally, many children “outgrow” the diagnosis before adulthood.

Most published series indicate that cyclic vomiting syndrome lasts an average of 2.5-5.5 years, resolving in late childhood or early adolescence. A few patients continue to be symptomatic through adulthood.

As early as 1898, clinicians observed that some patients went on to develop migraine headaches. That some children with cyclic vomiting syndrome progress to abdominal migraines and then to migraine headaches implies that there may be a sequential progression of age-dependent manifestations of migraine.

A survey by Abu-Arafeh et al ⁴⁰ found the mean ages of children with cyclic vomiting syndrome, abdominal migraines, and migraine headaches to be 5.3 years, 10.3 years, and 11.5 years, respectively. This finding supports the developmental progression from vomiting to abdominal pain to headache. In unpublished data, Li and Hayes determined that nearly one third of patients develop migraines after resolution of cyclic vomiting syndrome and predicted that nearly 75% would develop migraines by age 18 years.

A study of 31 patients with cyclic vomiting syndrome by Hikita et al ⁴¹ found that the median overall duration of the disorder was 66 months and that 44% of the patients seen for follow-up (25 patients) developed migraine. The authors also found abnormally high adrenocorticotropic hormone and antidiuretic hormone levels among the 25 patients for whom follow-up data were available. Significant correlations between attack duration and adrenocorticotropic hormone levels and attack duration and antidiuretic hormone levels were noted.

Although patients are well about 90% of the time, cyclic vomiting syndrome can be medically and socially disabling. More than 50% of patients require intravenous (IV) fluids, compared with less than 1% of patients with rotavirus gastroenteritis. The average annual cost of testing, treatment, and absenteeism totals $17,000. Children miss an average of 24 school days per year and often need home tutoring or, occasionally, home schooling. Additionally, because of its frequency during times of excitement, cyclic vomiting syndrome has ruined many birthdays, holidays, and vacations ²⁸.

In adults, substantial morbidity is associated with cyclic vomiting syndrome, perhaps because of lack of awareness and resultant delays in diagnosis. In a study of 41 cyclic vomiting syndrome patients, Fleisher found that 32% were completely disabled at the time of diagnosis ⁴². A total of 293 procedures were performed in the 41 patients, and none were indicative of organic etiology. In addition, 17 surgical procedures, including 10 cholecystectomies, appendectomies, exploratory laparotomies, a pyloroplasty, and a hysterectomy, were performed without any therapeutic benefit.

Adults and children with cyclic vomiting syndrome also have multiple emergency department (ED) visits (see Table 1 below), and the diagnosis is often unrecognized ⁴³.

Table 2. Characteristics of emergency department visits in patients with cyclic vomiting syndrome

Characteristic	Adults (n = 104)	Children (n = 147)
Number of emergency department visits per patient with cyclic vomiting syndrome (median)	15 (range, 1-200)	10 (range, 1-175)
Number of emergency department visits before diagnosis of cyclic vomiting syndrome (median)	7 (range, 1-150)	5 (range, 0-65)
Diagnosis not made in emergency department	89 (93%)	119 (93%)
Diagnosis not recognized in emergency department in patients with established diagnosis of cyclic vomiting syndrome	84 (88%)	97 (80%)
Number of different emergency departments visited (mean ± standard deviation)	4.69 ± 4.72	2.6 ± 2.42

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