What is cyclic vomiting syndrome

Cyclic vomiting syndrome, is a functional gastrointestinal disorder (no apparent cause) that causes sudden, repeated attacks—called episodes—of severe nausea, vomiting and tiredness (lethargy) ¹. Episodes can last from a few hours to several days. The episodes are separated by periods without nausea or vomiting. The time between episodes can be a few weeks to several months. Episodes can happen regularly or at random. 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.

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.

The 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
• Severe nausea
• Intense sweating

Other signs and symptoms during a vomiting episode may include:

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

The time between vomiting episodes is usually symptom-free.

People with cyclic vomiting syndrome may have other health problems, including ²:

• 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 ².

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 ³. 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.

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.

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. 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.

Each episode of cyclic vomiting syndrome tends to start at the same time of day, last the same length of time, and happen with the same symptoms and intensity as previous episodes. Episodes may begin at any time but often start during the early morning hours.

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

• retching—trying to vomit but having nothing come out of your mouth, also called dry vomiting
• pain in the abdomen
• abnormal drowsiness
• pale skin
• headaches
• lack of appetite
• not wanting to talk
• drooling or spitting
• extreme thirst
• sensitivity to light or sound
• dizziness
• diarrhea
• fever

Cyclic vomiting syndrome causes

Experts aren’t sure what causes cyclic vomiting syndrome. However, some experts believe the following conditions may play a role:

• 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

Although the causes of cyclic vomiting syndrome have yet to be determined, researchers have proposed several factors that may contribute to the disorder. These factors include changes in brain function, hormonal abnormalities, and gastrointestinal problems. Many researchers believe that cyclic vomiting syndrome is a migraine-like condition, which suggests that it is related to changes in signaling between nerve cells (neurons) in certain areas of the brain. 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, cystic vomiting syndrome is often classified as a type of dysautonomia.

Some cases of cyclic vomiting syndrome, particularly those that begin in childhood, may be related to changes in mitochondrial DNA. 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 this condition.

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.

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.

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 treat their symptoms.

However, cannabis 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 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 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 ⁴:

• 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 ⁵:

• 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.

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.

Imaging tests

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

• Ultrasound of the abdomen.
• 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.
• MRI scan or CT scan of the brain.

Cyclic vomiting syndrome treatment

Treatment goals in cyclic vomiting syndrome are to identify and avoid triggering factors, prevent recurrent acute episodes with prophylactic medication therapy, ameliorate acute episodes with abortive treatment and supportive care, and provide psychological support to the patient and family ⁶. Though 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 ⁷. 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

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 ⁸. 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 ⁸. 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 ⁵.

Taking medicines early in this 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 this 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.

Remission phase

The goal of therapy for remission phase is prophylaxis of further episodes ⁹. Antidepressant, antiepileptic, and anti-migraine pharmacotherapies show an overall reduction or remission of cyclic vomiting syndrome symptoms in more than 70% of patients ¹⁰.

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 ¹¹.

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 ¹². 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%) ¹².

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 ¹³. Several case series have found L-carnitine effective ¹⁴.

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 ¹⁵, gonadotropin releasing hormone analogue ¹⁶, mirtazapine ¹⁷, onabotulinumtoxinA ¹⁸, and risperidone ¹⁹.

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.

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