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Cyclic vomiting syndrome

Author: B UK Li, MD
Section Editors: Nicholas J Talley, MD, PhD, Marc C Patterson, MD, FRACP, Melvin B Heyman, MD, MPH
Deputy Editor: Alison G Hoppin, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: May 2021. | This topic last updated: Jun 11, 2020.

INTRODUCTION

Cyclic vomiting syndrome (CVS) is an idiopathic disorder characterized by recurrent, stereotypical bouts
of vomiting with intervening periods of normal or baseline health [1]. Both children and adults are
affected, although the clinical presentation and natural history vary somewhat with age [2-6].

CVS was first described in the late 1800s [7,8]. The key features are [9,10]:

● Recurrent discrete episodes of vomiting

● Varying intervals of completely normal (or baseline) health between episodes
● Episodes are stereotypical with regard to timing of onset, symptoms, and duration
● The vomiting is not attributable to other disorders

This topic review will provide an overview of CVS in children and adults. Treatment guidelines have been
published for children [9] and adults [10]. Overviews of other causes of vomiting are presented
separately. (See "Approach to the infant or child with nausea and vomiting" and "Approach to the adult
with nausea and vomiting".)

EPIDEMIOLOGY

CVS is no longer considered to be rare in children or adults.

The prevalence of CVS in children is estimated at 1.9 to 2.3 percent, with an incidence of 3.2 per 100,000
population, based on studies in predominantly White populations [11-13]. The average age was 9.6 years
at the time of diagnosis, while the average age at the onset of symptoms was 5.3 years. CVS appears to
be somewhat more common in girls than boys, with a ratio of 55:45 [1,9,14-18]. CVS is highly associated
with a history of migraines, either in the patient or (especially in children) a maternal family member (72
to 82 percent) [19]. A family in which CVS appears to be inherited has been described [20].

The prevalence of CVS in adults appears to be similar to that in children. As examples, CVS represented
10.8 percent of functional gastrointestinal disorders seen in an adult gastroenterology clinic and 2
percent in a population survey [21,22]. One of the largest studies included 101 adult patients seen during
a six-year period at an academic medical center [23]. Adult patients could be divided into subgroups with
pediatric-onset or adult-onset of CVS, in which symptoms began at a mean age of 13 versus 32 years,
respectively [2,23]. These groups differed significantly in sex predominance (86 percent female in
pediatric-onset versus 57 percent female in adult-onset disease). Another study found that the CVS
began at an average age of 35 (range 14 to 73 years) but was not diagnosed until patients were on
average 41 years old [24]. Compared with children, adults with CVS tend to have less frequent episodes
but with far longer duration. (See 'Adults' below.)

PATHOGENESIS

The pathogenesis of CVS remains unknown; however, it appears to be multifactorial, with several
potential pathways. An association between CVS and migraine headaches has been most consistently
described in children and adults, suggesting that there may be a common pathophysiologic process.
However, CVS has also been linked to autonomic abnormalities (elevated sympathetic tone and impaired
parasympathetic regulation), hypothalamic-pituitary-adrenal activation (Sato variant), mitochondrial
dysfunction, menses (estrogen sensitivity), food allergy, and cannabis use [1,25]. One review notes that
chronic migraine, epilepsy, panic disorder, and CVS have similar temporal patterns and triggers and
posits a neuroexcitability threshold, which when exceeded (due to enhanced susceptibility plus acute
stressors), triggers episodic attacks of vomiting [25].

Association with migraines — CVS has been linked to migraine headaches and abdominal migraine (
table 1) [26,27]. This association is based upon the discreteness of episodes, the progression from
cyclic vomiting to migraine headaches in many patients, the presence of a strong family history of
migraine headaches in affected children (approximately 80 percent), and the response to antimigraine
therapy in up to 80 percent of children [9,19]. In adults, CVS is also associated with a personal history (43
percent) or family history (64 percent) of migraines and often responds to antimigraine therapy [2].
Underlying sympathetic autonomic dysfunction may predispose children and adults to both CVS and
migraine headaches [23,28,29]. (See "Pathophysiology, clinical features, and diagnosis of migraine in
children".)

Cross-sectional prevalence data suggest that CVS (which predominates at a mean age of five years) often
progresses to abdominal migraines (mean age nine years), which in turn lead to migraine headaches
(mean age 11 years) [11]. However, many children progress directly from CVS to migraines. (See 'Natural
history' below.)

Mitochondrial dysfunction — Mitochondrial disorders of fatty acid oxidation (eg, medium-chain acyl-

coenzyme A dehydrogenase deficiency), respiratory chain defects (eg, MELAS [mitochondrial
encephalomyopathy, lactic acidosis, and stroke-like episodes]), and mitochondrial DNA deletions can be
associated with episodes of metabolic crisis and vomiting, usually triggered by infection or prolonged
fasting [30]. (See "Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features" and
"Mitochondrial myopathies: Clinical features and diagnosis".)

The hypothesis that mitochondrial dysfunction contributes to CVS in some patients is suggested by
findings of maternal inheritance of two common mitochondrial DNA polymorphisms, 16519T and 3010A,
reported in approximately one-half of White children with CVS with haplotype H [31,32]. This association
appears to be common in children but not in adults. Further support comes from clinical observations of
the efficacy of mitochondrial-targeted therapies, coenzyme Q10 [33,34] and L-carnitine [33-35], in CVS.
This hypothesis is further strengthened by an association of both CVS and migraine headache with the
same two mitochondrial DNA polymorphisms [36]. Sequencing of nuclear DNA suggests that there may
be synergistic polymorphisms in some genes (RYR2, SCN4A) that impact cellular stress responses in CVS
[37].

Autonomic dysfunction — Children and adults with CVS have been found to have augmented
sympathetic tone with low to normal parasympathetic tone [23,28]. Adolescent patients are frequently
found to meet criteria for postural orthostatic tachycardia syndrome (POTS), and treatment of that
comorbid condition can help prevent episodes of vomiting [1,29]. Patients who have a hereditary sensory
autonomic neuropathy (such as Riley-Day syndrome) sometimes have clinical episodes resembling CVS.
(See "Hereditary sensory and autonomic neuropathies".)

Hypothalamic-pituitary-adrenal axis hyperreactivity — A subset of children with CVS have prolonged

and severe episodes, associated with profound lethargy and intra-episodic hypertension, known as the
Sato variant [38]. These children also have intra-episodic elevations of corticotropin, cortisol, vasopressin,
prostaglandin E2, and catecholamines, suggesting hypothalamic-pituitary-adrenal axis hyperreactivity.
Animal studies suggest that CVS may be a brain-gut disorder in which corticotropin-releasing factor
triggers gastric stasis and vomiting by vagal stimulation [39].

Association with rapid gastric emptying or gastroparesis — In adults, gastric emptying may be
accelerated or sometimes delayed in CVS, but any association with symptoms is controversial. One
hypothesis is that rapid gastric emptying is a marker for underlying dysautonomia [23,40]. Paradoxically,
there may be an overlap between CVS and idiopathic gastroparesis in adults. Testing of gastric emptying
to exclude gastroparesis may be considered if cyclic vomiting symptoms are refractory to therapy [40,41]
(see 'Adults' below). Gastric emptying is generally normal in children with CVS [42].

Estrogen sensitivity (catamenial CVS) — Similar to menstrual migraine headaches, some adolescent

girls (22 percent) develop CVS at the onset of their menstrual periods (catamenial CVS). This
phenomenon is postulated to be the result of the premenstrual drop in estrogen, and many patients with
this pattern respond to treatment with low-dose estrogen, progesterone-only oral contraceptives, or a
medroxyprogesterone acetate intramuscular injection every three months. An association between CVS
and menses has also been described in adults [24]. (See 'Catamenial cyclic vomiting syndrome' below.)

Chronic cannabis use — Cannabis hyperemesis syndrome (CHS) is characterized by episodic vomiting

associated with prolonged (2 to 10 years), high-dose (nearly daily) recreational cannabis use and that
resolves with cannabis cessation [5]. This disorder primarily affects young adult and adolescent males, as
described in growing numbers of case series [22,43-50].

Circumstantial evidence suggests that CHS is a subset of CVS that is triggered by prolonged, high-dose
cannabis exposure, although the distinction between the disorders is often unclear [10,50]. Both CHS and
CVS are associated with characteristic, repetitive hot-water bathing behavior, which is seen during the
cannabis-associated vomiting cycles [43,47] as well as in typical CVS attacks in both adults (48 percent)
and children who have not been exposed to cannabis [51]. However, reverse causality is also possible
since many adults with CVS self-medicate with cannabis to alleviate their daily nausea, and this can be a
source of diagnostic confusion.

For patients with CVS-like symptoms who use cannabis, we suggest a trial of prolonged abstinence from
cannabis. The duration of cannabis cessation needed to exclude a diagnosis of CHS is not well defined in
the literature. A report from experts in CVS suggests that symptom resolution with cannabis abstinence
for six months or three typical CVS cycles is needed for diagnosis of CHS. A presumptive diagnosis of CHS
can also be made for patients unable to abstain from cannabis products [50]. Of note, patients who do
not experience long-term resolution of symptoms following prolonged abstention from cannabis should
be diagnosed with CVS rather than CHS. Certainly, if emetic episodes persist despite abstention from
cannabis, then further work-up for CVS should be undertaken and corresponding treatment trialed.

Food sensitivity — Foods that trigger CVS in some patients include chocolate, cheese, and monosodium
glutamate, similar to the triggers that have been reported for migraines. However, the commonly-held
association with dietary triggers has been called into question in blinded provocative trials [52]. If a
causal association has not been established, we suggest a trial of avoidance only if the clinical history
suggests that a food is a trigger for an individual patient (see "Pathophysiology, clinical manifestations,
and diagnosis of migraine in adults", section on 'Precipitating and exacerbating factors'). Sensitivity to
cow's milk, soy, and egg white protein has also been reported to trigger CVS attacks in some children
[14].

CLINICAL MANIFESTATIONS

The essential features of CVS are recurring episodes of vomiting with a stereotypical pattern regarding
time of onset (acute) and duration (hours to days), accompanying symptoms and signs (eg, pallor,
lethargy), and the absence of vomiting between episodes ( table 2). Other common features include a
history in the patient or family history of migraine headaches; the self-limited nature of the attacks;
associated symptoms of nausea, abdominal pain, headache, motion sickness, and photophobia; and
associated signs of profound lethargy and pallor (especially in children), excess salivation, diarrhea,
dehydration, and social withdrawal. (See 'Diagnosis' below.)

Children and adolescents — In children and adolescents, the specific pattern of vomiting episodes is
variable but usually remains stereotypical for an individual patient [1,4]. In general, CVS episodes tend to
begin in the early morning hours (2:00 to 7:00 AM) and last approximately the same duration. Most have
a prodromal period of pallor, anorexia, nausea, abdominal pain, and/or lethargy ( table 2). The attacks
usually last an average of 24 to 48 hours, although they may last up to 7 to 10 days. Approximately one-
half of children have attacks at regular intervals, commonly occurring every two to four weeks, while the
remainder have unpredictable intervals between episodes. Approximately three-quarters of parents can
identify triggers, which are usually psychological (typically more excitement, eg, birthdays, rather than
negative stressors) or infectious (eg, upper respiratory) events [53].

The clinical picture of CVS has gradually expanded to recognize that the recurring vomiting is often
accompanied by multiple comorbid conditions that affect the patient even between vomiting episodes:

● Anxiety – The most prevalent comorbidity is anxiety, which affects 47 percent of (59 percent of
school-aged) children with CVS [54]. In fact, the lower health-related quality of life in CVS patients
correlated with trait anxiety and coping abilities rather than with medical severity (frequency,
duration of episodes) [54].

● Postural orthostatic tachycardia syndrome (POTS) – POTS is common in adolescents with CVS (14
percent in one pediatric case series and 38 percent of screened adolescents [55]). There is evidence
of altered autonomic tone at baseline with elevated sympathetic tone and low to normal
 parasympathetic tone [28,29] (see 'Autonomic dysfunction' above). Management of POTS in
adolescents with CVS, consisting of fluid and salt supplementation, fludrocortisone and low-dose
propranolol, can reduce the frequency of vomiting episodes [29].

● Coalescent CVS – Some pediatric patients initially have a typical episodic pattern of CVS but later
develop chronic daily nausea between vomiting episodes. The nausea typically peaks in the morning,
affects approximately 12 percent of pediatric patients with CVS, and is most common in adolescent
girls [33,55]. Some may outgrow the episodic vomiting entirely, and the persisting nausea may be
then diagnosed as functional nausea. In the absence of an effective antinausea agent, it is difficult to
treat. Anecdotally, amitriptyline and doxylamine-pyridoxine improve symptoms for some patients
[56]. The term "coalescent" CVS has been used to classify this pattern in pediatric patients, although
the term is imprecise and is not a pattern generally observed in adult patients.

Adults — In adults, 93 percent described a prodrome of nausea, epigastric pain, or headache; early
morning onset; abdominal pain during episodes; and a high peak rate of vomiting of eight emeses per
hour during the emetic phase [51]. Other common features include erosive esophagitis during or shortly
after a vomiting episode (50 percent), association with menstrual cycles or pregnancy, and a history of
migraine headaches in self or family [2,23,24]. Postural orthostatic tachycardia may be present. In two
series of adults with CVS, approximately one-third experienced either orthostatic tachycardia or
hypotension [23,40].

Although there are similarities in CVS across age groups [15], some key differences between adults and
children have been observed ( table 2) [24]:

● Frequency – Adult patients with adult-onset CVS tend to have less frequent symptoms compared with
adult patients with pediatric-onset CVS (approximately four cycles per year, compared with 12 cycles
per year, respectively) [51].

● Duration – Adults tend have longer episodes of CVS compared with children (mean duration six
versus two days).

● Age of onset – The age of onset is highly variable in adults, while in children, the age of onset is often
in the toddler or preschool years.

● Triggers – Triggering events may be less common in adults.

● Interepisodic nausea – Nausea between episodes is more common in adults compared with children
(40 to 63 percent versus 12 percent) ( figure 1) [51].

● Behavioral symptoms – Two notable behaviors are more common in adults than in children: the use
of hot-water showers or bathing to attenuate the nausea (56 percent), even in the absence of
cannabis use, and rapid drinking of fluids followed by vomiting (apparently to dilute the bitterness of
the bile). These behaviors do not indicate a factitious or psychiatric etiology [57]. Nearly one-half (44
percent) of adults with CVS had a history of physical or sexual abuse as a child, and two-thirds have
had panic anxiety [4].

Case series of adult patients with CVS reflect difficulty and delays in establishing the diagnosis, often with
repeat imaging and endoscopic studies and sometimes with surgical procedures such as
cholecystectomy, pyloroplasty, or fundoplication without improvement [2,24,51]. This may reflect the
frequent presence of interepisodic symptoms between acute vomiting episodes in adults with CVS and
the limited awareness of CVS among clinicians caring for adults.

There may be an overlap between CVS and idiopathic gastroparesis in adults. Approximately 11 percent
of adults with idiopathic gastroparesis have a cyclic pattern of symptoms and some respond to tricyclic
antidepressants, similar to patients with CVS [58]. (See "Gastroparesis: Etiology, clinical manifestations,
and diagnosis".)

NATURAL HISTORY

Many children outgrow CVS by their preteen or early teenage years [59]. However, we have estimated
that up to 75 percent of children with CVS will then develop migraine headaches by age 18 [1,19]. Some
children who progress from CVS to migraine headaches will first pass through a phase of abdominal
migraines [60]. Abdominal migraines can be distinguished from CVS in that the core symptom of
abdominal migraines is abdominal pain, with little or no vomiting. Both syndromes may have headache
as a feature and respond to antimigraine therapy [1]. One retrospective study of 51 children followed for
up to 13 years found that vomiting resolved in 60 percent [61]. However, despite resolution of vomiting,
42 percent continued to have regular headaches and 37 percent had abdominal pain.

The natural history in adults has not been well studied. In the series of 17 adults described above [24], 13
had at least a partial response to tricyclic antidepressant therapy, while an additional three responded to
other types of treatment. One patient had resolution off of medication during two years of follow-up.
Nonresponders to tricyclic antidepressants compared with responders were more likely to have
coalescent symptoms, have poor compliance, use narcotics, have more severe symptoms with longer
episodes, and have more emergency department visits [2,23].

DIAGNOSIS

CVS remains a diagnosis based upon the history and exclusion of alternative diagnoses ( table 3). Two
sets of criteria have been proposed based upon a consensus of experts:

Pediatric criteria — The pediatric criteria for diagnosis of CVS developed by the North American Society
for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) require all of the following
[6,9,62]:

● At least five attacks in any interval or a minimum of three attacks during a six-month period
● Episodic attacks of intense nausea and vomiting lasting one hour to 10 days and occurring at least
one week apart
● Stereotypical pattern and symptoms in the individual patient
● Vomiting during attacks occurs at least four times per hour for at least one hour
● Return to baseline health between episodes
● Not attributed to another disorder

The NASPGHAN guideline summarizes the diagnostic process in an algorithm ( algorithm 1) [9].

A separate set of diagnostic criteria for CVS were developed in 2016 (pediatric Rome IV criteria) [6,62].
These differ from the NASPGHAN criteria by including those children with a minimum of two episodes
and eliminating the quantitative severity of vomiting of as least four times per hour at the peak. These
criteria could result in a higher sensitivity but possibly lower specificity than the NASPGHAN criteria.

Adult criteria — Criteria for diagnosis of CVS in adults (adult Rome IV criteria) are [5]:

● Stereotypical episodes of vomiting regarding onset (acute) and duration (less than one week)
● Three or more discrete episodes in the prior year and two episodes in the past six months, occurring
at least one week apart
● Absence of vomiting between episodes, but other milder symptoms can be present between cycles

A history or family history of migraine headaches further supports the diagnosis.

Exclusion of other causes of vomiting — CVS should be considered among other diagnoses in patients
presenting with nausea and vomiting. (See "Approach to the adult with nausea and vomiting" and
"Approach to the infant or child with nausea and vomiting".)

Alarm symptoms and signs — Alarm symptoms and signs alerting the clinician to a diagnosis other
than CVS include the following; these were developed in the pediatric consensus statement but generally
apply to adults as well [9]:

● Gastrointestinal
• Gastrointestinal bleeding (other than mild hematemesis developing during an episode of
vomiting, which suggests a prolapse gastropathy or Mallory-Weiss tear)
• Unilateral abdominal pain
• Bilious vomiting (bilious vomiting is fairly common in CVS but warrants further evaluation to
exclude intestinal obstruction)
• Weight loss

● Metabolic
• In toddlers, episodes triggered by fasting, illness, or high-protein meal, or by marked anion gap
acidosis, hypoglycemia, or hyperammonemia

● Neurologic
• Severe headaches (especially if continuous or worsening rather than episodic)
• Altered mental status
• Gait disturbances or other new neurologic signs

● Other
• Severe clinical course characterized by failure to respond to treatment, progressive worsening,
prolonged episodes requiring hospitalization
• A change in the vomiting pattern or symptoms

Considerations for children — Further steps depend upon the absence or presence of warning signs:

● Alarm signs absent – Children who present with the typical symptoms of CVS as outlined above and
with no warning symptoms require only a limited screening evaluation to exclude other disorders:

• Imaging – An upper gastrointestinal series to the ligament of Treitz should be performed in all
children to exclude intestinal malrotation or nonfixation with possible intermittent volvulus [63].
(See "Intestinal malrotation in children".)
 • Laboratory testing – During at least one episode, laboratory testing should be performed,
consisting of electrolytes, glucose, blood urea nitrogen (BUN), creatinine, and urinalysis. The
primary purpose of these tests is to monitor for hypovolemia and electrolyte disturbances that
can result from protracted vomiting, and chronic renal or Addison disease. Mild metabolic
acidosis, hypoglycemia, and ketosis are consistent with CVS. Severe acidosis or hypoglycemia
warrant further evaluation for an inborn error of metabolism, especially in infants and toddlers.
(See "Metabolic emergencies in suspected inborn errors of metabolism: Presentation,
evaluation, and management".)

• Trial of prophylactic therapy – For patients whose symptoms warrant a trial of prophylactic
therapy, the diagnosis of CVS is further supported if the CVS improves. Children who do not
respond to prophylactic therapy may warrant further evaluation to identify other possible causes
of the symptoms. (See 'Prophylactic medications' below.)

For children with no alarm signs and typical symptoms, a provisional diagnosis of CVS can be made
on the basis of the clinical history and basic testing outlined above. An extensive evaluation is not
recommended because of low yield and high costs [1,64]. As an example, among 225 children with
recurring cyclical episodes of vomiting who were evaluated extensively, only one in eight were found
to have an underlying disorder that required intervention [65]. In a separate study, the results of
systematic laboratory, radiographic, and endoscopic testing (cost of $6125 per child) altered
management in only 4 percent [64]. A cost-decision analysis concluded that a more cost-effective
diagnostic strategy in children was to obtain an upper gastrointestinal series to rule out malrotation
and the possibility of subsequent volvulus, followed by a two-month trial of antimigraine therapy,
with further studies reserved for those with continued symptoms [63].

● Alarm signs present – In the presence of alarm signs, further evaluation is recommended:

• Acute-onset unilateral or flank pain – Perform an abdominal ultrasound to exclude acute

hydronephrosis (so-called Dietl crisis). In a case series of four children, acute hydronephrosis
caused by ureteropelvic junction obstruction closely mimicked symptoms of CVS [66]. (See
"Congenital ureteropelvic junction obstruction", section on 'Older children'.)

• Metabolic warning signs – For young children with characteristics suggesting metabolic disease
(eg, episodes triggered by fasting, illness or a high-protein meal), measure serum concentrations
of lactate, pyruvate, ammonia and serum amino acids, and urine organic acids. These tests
should be performed during the early part of the episode, before intravenous fluids are
administered.

• Neurologic signs – Perform a computed tomography (CT) or magnetic resonance imaging (MRI)
scan of the brain.

• Upper gastrointestinal bleeding – If upper gastrointestinal bleeding is severe or persistent,

perform an endoscopic evaluation. Patients with CVS may have endoscopic evidence of prolapse
gastropathy or Mallory-Weiss tear due to repetitive forceful vomiting.

• Upper gastrointestinal symptoms that persist between episodes – Perform an upper endoscopy
between episodes. If endoscopy is performed during or shortly after an episode of CVS, The
presence of esophagitis does not imply that reflux is an underlying cause, since one-half of
patients with CVS have esophagitis but will not respond to antireflux measures.
 Considerations for adults — In adults, guidelines recommend biochemical, endoscopic, and
sometimes radiographic assessments [10]:

● Biochemical testing is recommended to include a complete blood count, serum electrolytes, glucose,
hepatic aminotransferases and pancreatic lipase, and urinalysis.

● An esophagogastroduodenoscopy is also recommended, even though common findings of Mallory-

Weiss tear and mild esophagitis are likely to be epiphenomenon.

● Imaging should be performed for selected patients, including a right upper quadrant ultrasound for
patients with focal pain in that area, or CT or magnetic resonance enterography for patients with
clinical symptoms suggesting the possibility of intestinal obstruction, such as suspicious signs on a
conventional radiograph or high-pitched bowel sounds.

MANAGEMENT

Management of CVS involves:

● Lifestyle interventions, to reduce the risk of inducing an attack.

● Supportive care, provided during any severe bout of cyclic vomiting. This may include admission to
the emergency department and/or hospital, intravenous fluids, antiemetics (including those with
beneficial sedating effects), and analgesics. (See 'Supportive care' below.)

● Abortive medication used during the prodrome to prevent or attenuate the attack. This approach
may be sufficient for patients with relatively mild or infrequent symptoms. (See 'Abortive
medications' below.)

● Prophylactic medication for selected patients, given daily to prevent further episodes. This
approach is generally reserved for patients with frequent prolonged or severe symptoms. (See
'Prophylactic medications' below.)

The recommendations for management are summarized in the tables ( table 4A-C). Referral to a
pediatric gastroenterologist, neurologist, or metabolic specialist is indicated for children with frequent or
severe disabling episodes or mild episodes that persist despite lifestyle changes, supportive care, and a
therapeutic trial. Similarly, adults should be referred to a specialist familiar with CVS if episodes are
severe or disabling and initial interventions are not effective. Management of CVS in adults is outlined in
the algorithm ( algorithm 2).

Lifestyle interventions — Lifestyle modifications to reduce the risk of inducing an attack include

adequate fluid intake, avoidance of fasting, using long-acting caloric snacks, good sleep hygiene, and
regular exercise. Recognized precipitating factors should be avoided whenever feasible. In children,
common triggers include physical exhaustion from lack of sleep, stressors such as bullying at school,
motion (car rides, amusement park rides), fasting, and certain foods (eg, chocolate, cheese, cow's milk).
In adults, precipitating factors are somewhat less common than in children but may include sleep
disruptors (shift work, extended travel across time zones) and psychological stressors related to
interpersonal conflict at work or home. If there as a history or prolonged and frequent cannabis use,
total abstention can clarify whether this is cannabis hyperemesis syndrome (CHS) or CVS.
Management should address comorbid conditions as well. First among them is anxiety, panic attacks, or
depression, which are present in 30 to 50 percent of children or adults with CVS [10,67,68]. Referral to a
medical psychologist for cognitive behavioral therapy is an integral part of our treatment plan, and
behavioral intervention can result in marked improvement and reduced school absenteeism and
functional disability. In more severe cases, the addition of anxiolytic agents (eg, citalopram, sertraline)
may be necessary. If school absenteeism fails to respond to a graded school-reentry plan, a
comprehensive biobehavioral rehabilitation program may be needed for recovery.

Supportive care — Supportive or rescue care is provided during an episode of vomiting to alleviate

symptoms and complications. Once the vomiting becomes well established after several hours, the
episode typically cannot be aborted and must run its usual course. The goal then becomes one of
alleviating symptoms including vomiting, nausea, abdominal pain, and headache and replenishing fluid,
energy, and electrolytes.

For supportive care of patients with CVS, the following strategies are often used, based on limited
evidence ( table 4B) [10,69]:

● Intravenous hydration – Intravenous hydration can decrease the frequency of vomiting and
duration of episodes [70] in approximately one-half of patients, based on clinical experience [69].

• First, hypovolemia should be corrected with one or more fluid boluses (eg, isotonic saline 10 to
20 mL/kg, or 1 L in adults) as needed.

• Subsequently or simultaneously (piggy-backed), additional intravenous hydration should be

given using half-normal saline (0.45% NaCl) with 10% dextrose for children and normal saline
(0.9% NaCl) with 5% dextrose for adults [10]. The solution should be infused at 1.5 times the
maintenance rate. The rationale for including dextrose is that this may attenuate the catabolic
state and ketosis induced by the acute CVS episode, which can prolong vomiting. For patients
with significant electrolyte derangements (hypokalemia, hypochloremia, and hyponatremia),
adjustments to intravenous fluids are discussed separately. (See "Treatment of hypovolemia
(dehydration) in children" and "Maintenance and replacement fluid therapy in adults".)

In children, persistent moderate to severe anion gap acidosis or hypoglycemia should prompt
further evaluation for a metabolic disorder, even though striking elevations of urinary acetoacetate
and beta-hydroxybutyrate (on organic acid profiles) can be found during episodes of CVS. (See
'Considerations for children' above.)

● Environment – Some patients benefit from staying in a quiet, dark room with limited vital sign
checks to reduce stimulation, which can exacerbate episodes.

● Feeding – Provision of calories during the emetic phase is thought to help children with
mitochondrial variants of CVS and suspected disorders of carbohydrate or fat metabolism. However,
most children can only tolerate delivery by parenteral or jejunal routes, which is usually not feasible
unless the patient has a jejunal access device in place. Once vomiting has ceased during the
recovery, initiation of frequent small feedings with low-fat foods is important for nutritional
rehabilitation. (See 'Mitochondrial dysfunction' above.)

● Antiemetics – Use of ondansetron, a 5-hydroxytryptamine (5-HT3) receptor antagonist, is

recommended for use in emergency and inpatient settings to reduce the frequency of emesis and
 fluid requirements [69]. Parenteral ondansetron, even if administered early, may attenuate the
vomiting but usually does not abort the episode and does not reduce the unrelenting nausea. In the
available cases series, 50 to 75 percent of patients reported improvement with intravenous
ondansetron [19,69,70].

Dosing for ondansetron is:

• Children – 0.3 mg/kg/dose, up to a maximum of 16 mg for the initial dose for adolescent
patients without risk factors for QTc prolongation. May give an additional dose (maximum 8 mg)
every four to six hours, with a maximum total dose of 32 mg/24 hours.

• Adults – 8 mg intravenously; a 16 mg/dose may be used for the first dose for selected patients
<75 years old with no risk factors for QTc prolongation. May give an additional 8 mg dose every
four to six hours, with a maximum total dose of 32 mg/24 hours [71].

Risk factors for QTc prolongation include other medications that also prolong the QT interval,
including tricyclic antidepressants and phenothiazine antiemetics.

Triptan therapy (eg, sumatriptan) may be useful if the patient presents to the emergency department
in the very early phases of the episode (ie, within one hour of the onset of vomiting), but this is rarely
the case [10]. (See 'Abortive medications' below.)

● Sedating agents – Because vomiting is not completely controlled by a 5-HT3 antagonist therapy
alone, we usually add a medication with both antiemetic and sedating effects (eg, diphenhydramine
or lorazepam).

Data on the use of these medications in this setting are extremely limited. The practice of using
medications with a sedating effect is based largely on clinical observations that induction of deep
sleep may alleviate both nausea and vomiting in some cases or stop episodes already in progress.
Occasionally, administration of benzodiazepines or use of closely monitored general anesthesia
using dexmedetomidine will terminate an episode [72]. The efficacy of these medications for severe
and intractable vomiting is also supported by experience with these drugs in other settings (eg,
chemotherapy-induced nausea and vomiting, postoperative nausea and vomiting, cannabinoid
hyperemesis) [47]. In pediatric practice, we often begin with diphenhydramine and if sedation is
inadequate, we switch to lorazepam. Adult guidelines are similar but suggest initiating treatment
with lorazepam [10]. (See "Prevention and treatment of chemotherapy-induced nausea and vomiting
in adults" and "Postoperative nausea and vomiting" and "Cannabis (marijuana): Acute intoxication",
section on 'Cannabis hyperemesis syndrome'.)

● Antihypertensives – Most patients with mild hypertension during an acute CVS episode do not
require antihypertensive therapy, since the hypertension usually resolves as the patient's discomfort
improves. A small subset of patients (those with the Sato variant of CVS) may present with more
severe and persistent hypertension (see 'Hypothalamic-pituitary-adrenal axis hyperreactivity' above).
If pharmacologic therapy is needed for such patients, short-acting antihypertensives can be used as
needed during the episode. Prolonged use of antihypertensives is not necessary, because the
hypertension abates with resolution of the CVS episode.

● Other medications – Management of abdominal and headache pain usually begins with the
nonsteroidal antiinflammatory drug intravenous ketorolac. This approach is supported by our clinical
 experience and the theoretical mechanism that it reduces elevated prostaglandin E2. Oral or
intravenous acetaminophen also may be trialed but may be less effective than ketorolac, based on
anecdotal clinical experience. If possible, narcotics should be avoided as they can worsen vomiting
and induce dependence over time.

For adults, there is only anecdotal experience on the efficacy of the above antiemetics, sedating agents,
and analgesics used for supportive care [73-75]. A variety of other antiemetic medications have been
used, including high-dose dexamethasone, metoclopramide, and naloxone, but these are usually
unsuccessful [73].

Abortive medications — Abortive medications should be administered to any patient with known CVS if
they can be given during the prodrome or shortly after the vomiting begins. Abortive therapy alone is
generally suggested for patients with relatively mild or infrequent episodes. For those with frequent or
severe symptoms, abortive therapy may be used in conjunction with ongoing prophylactic therapy. (See
'Prophylactic medications' below.)

The primary choices for abortive medication in both children and adults are sumatriptan and aprepitant
(a neurokinin 1 antagonist) ( table 4B).

Children and adolescents

● Sumatriptan – For children with migraine-associated CVS, sumatriptan is moderately effective if

given early in the prodromal phase and may have some effect if given within one hour after onset of
vomiting. In one small case series, sumatriptan had a 54 percent response rate when given
subcutaneously and 33 percent when given intranasally [76]. It may be tried in those without a family
history of migraines because it can be effective in some. It appears to be more effective when the
episodes are shorter in duration (<1 day) in children. Our approach is to first do a trial by the
intranasal route. If symptoms persist, the dose can be repeated once in two hours. However, if
intranasal administration fails to alleviate symptoms, we may proceed to a trial of a subcutaneous
sumatriptan injection during the next episode of vomiting. In general, sumatriptan either is
completely effective or wholly ineffective in terminating an episode.

Sumatriptan dosing is not well established, especially for young children. We use the following doses
for CVS, based on clinical experience and a few published case series [76,77]:

• Age 5 to 11 years, or weight 20 to 39 kg – Intranasal dose 5 to 10 mg or subcutaneous dose 2 to

3 mg

• Age 12 to 17 years, or weight 40 to 59 kg – Intranasal dose 10 to 20 mg or subcutaneous dose 3

to 6 mg

• Age ≥18 years, or weight ≥60 kg – Intranasal dose 20 mg or subcutaneous dose 6 mg

A repeat dose may be given in two hours for intranasal administration and one hour for
subcutaneous administration. The nasal form causes a bitter aftertaste, which can be lessened by
flexing the head forward to avoid dripping spray into the nasopharynx. The subcutaneous dose can
induce a pronounced transient burning in the chest and neck region. Triptans are contraindicated in
those with known coronary or peripheral vascular disease and those with complex (eg, basilar)
migraines.
 ● Aprepitant – As an alternative, aprepitant, an oral neurokinin 1 antagonist antiemetic, can be used if
it can be given during the prodrome at least 30 minutes before the onset of vomiting with
subsequent dosing on days 2 and 3. Aprepitant is particularly appropriate for patients with no family
history of migraine or who failed to respond to triptans.

Abortive dosing of aprepitant varies by body weight:

• Children <15 kg – 80 mg orally on day 1 and 40 mg on days 2 and 3

• Children 15 to 20 kg – 80 mg orally once daily for three days
• Children >20 kg – 125 mg orally on day 1 and 80 mg on days 2 and 3

Among 25 children who were able to take oral aprepitant 30 minutes before vomiting, 76 percent
achieved at least a partial response [78]. Although there is only anecdotal, unpublished experience,
the use of intravenous fosaprepitant (phosphorylated prodrug) may be effective once vomiting has
begun. No significant side effects have been observed.

Adults — We suggest sumatriptan as the first-line abortive agent, using an intranasal dose of 20 mg
or subcutaneous dose of 6 mg ( algorithm 2). Based upon experience from treating migraines, the
subcutaneous route is likely more effective than the nasal one. If sumatriptan is not effective, the second-
line choice is a trial of aprepitant, using 125 mg orally on day 1 and 80 mg on days 2 and 3. These
suggestions reflect expert opinion, based on low-quality evidence from case reports and clinical
experience, as reviewed in the adult guideline [10].

Ondansetron administered orally before vomiting, beginning at home or intravenously in the emergency
department, rarely aborts an episode but can reduce the pace and amount of vomiting and may
circumvent the need for parenteral fluids [9]. (See 'Supportive care' above.)

Prophylactic medications — The decision to use prophylactic medications depends upon the frequency
and severity of the attacks, similar to the principles that guide treatment of patients with migraine
headaches [30]. In general, prophylactic therapy is warranted if attacks occur more than monthly or last
more than one to two days in a child or adolescent, or >4 episodes/year or last >2 days in an adult, or are
severe enough to require hospitalization or cause substantial school absenteeism or work disability.
Abortive therapy may be used in addition to prophylactic therapy for patients who continue to have
breakthrough vomiting episodes. (See 'Abortive medications' above.)

Children and adolescents — In children, agents that have been used prophylactically, with variable
success, include antimigraine agents (cyproheptadine, pizotifen, propranolol, amitriptyline, mirtazapine),
antiemetics (aprepitant), and anticonvulsants (phenobarbital, topiramate) [78-80]. Adjunctive treatment
with mitochondrial supplements (coenzyme Q10, L-carnitine, riboflavin) is often added to the
preventative regimen, based on limited evidence and with wide variation in practice [9,33-35,81].

We use the following approach to selecting prophylactic medications, consistent with the 2008 North
American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Consensus
Statement [9]. The limited evidence for the use of these medications for CVS suggests similar efficacy, so
selection among these medications is guided primarily by side effects and toxicities, as well as
differences in the amount of clinician experience with use of each drug for CVS within a specific age
group and indirect experience from their use for migraine.
● First-line – As the initial first-line choice for prophylactic therapy, we suggest the following (
table 4C):

• Children <5 years – Cyproheptadine or pizotifen. Pizotifen is similar to cyproheptadine and is

available outside of the United States.

• Children ≥5 years – Amitriptyline.

The use of cyproheptadine for prophylactic therapy in patients with CVS is supported by several small
case series. Response rates (ie, at least partial reduction in the frequency and/or severity of episodes
compared with baseline) reported in the available series range from 41 to 83 percent
[19,70,79,82,83]. Its use for CVS is also supported by indirect experience of its use for migraine
headaches in children. The recommendation favoring cyproheptadine over amitriptyline in younger
children was based primarily upon expert experience and respective side effect profiles.
Cyproheptadine is generally well tolerated by young children; side effects may include excessive
weight gain and sedation. Children should be monitored for these effects, and an alternative agent
should be considered in children who are already overweight. In some cases, tachyphylaxis may arise
and can be countered by intermittent dosing, achieved by either skipping this medication on
weekends or skipping one week per month. Outside of the United States, pizotifen, a similar agent,
may be used as first–line therapy, based on limited evidence [84]. (See "Preventive treatment of
migraine in children", section on 'Cyproheptadine'.)

The evidence supporting amitriptyline as a first-line agent includes several large case series in
children and adults, in which amitriptyline was the single most effective agent [2,9,19,79,85];
response rates in the available case series range from 70 to 90 percent [19,24,33,70,79,83].
Amitriptyline may be more effective for those with a personal or family history of migraine but
should be tried in those without a migraine association. In one case series, amitriptyline and other
antimigraine agents were effective in 79 percent of children with a history of migraines in the family
or patient, compared with 36 percent in those with no history of migraines [19]. (See "Preventive
treatment of migraine in children", section on 'Amitriptyline'.)

Optimal use of amitriptyline requires titration, monitoring (ie, electrocardiogram [ECG]), and, in some
cases, obtaining therapeutic blood levels, especially in children on higher doses. A common starting
dose is 0.25 to 0.5 mg/kg per day at bedtime, followed by increases in increments of 5 to 10 mg at
weekly intervals to a higher dose, often 1 to 1.5 mg/kg per day at bedtime. This incremental dose
increase allows for adaptation to side effects (eg, tiredness). Up to 50 percent of patients may
experience anticholinergic (dry mouth, constipation) and sedative side effects (morning tiredness).
ECG monitoring should be performed before starting and again 10 days after reaching the peak
dose; cardiotoxicity (tachyarrhythmia) can be avoided by maintaining the QTc interval <460 msec. It
typically takes up to one to two months for the effects of amitriptyline to become fully evident once
the target dose is reached. In some individuals, higher doses may be needed to control the CVS, but
this should be approached with caution. (See 'Nonresponders' below.)

● Second-line – If the first-line agents are not effective after optimal titration, the next step is a trial of
either aprepitant or propranolol ( table 4C). Aprepitant is a newer antiemetic agent that has good
efficacy based on limited but increasing clinical experience in adults and children. When aprepitant is
used for prophylaxis, it is administered at the following doses [78]:
 • Children <40 kg – 40 mg orally twice weekly
• Children 40 to 60 kg – 80 mg orally twice weekly
• Children >60 kg and adults – 125 mg orally twice weekly

Aprepitant is also used for abortive therapy, at higher doses, as described above. (See 'Abortive
medications' above.)

In one retrospective series of 16 children treated prophylactically with aprepitant, three (19 percent)
achieved a complete response and 10 (62 percent) achieved a partial response [78]. For propranolol,
response rates in the available case series range from 46 to 83 percent [9,19,70,82]. Propranolol was
recommended as the second-line agent in the NASPGHAN consensus statement, which was written
in 2008 before data on aprepitant became available [9]. Other agents that may be effective include
the anticonvulsants phenobarbital or topiramate, or the antidepressant mirtazapine [80,86,87].
Although all have similar rates of efficacy, we suggest aprepitant or propranolol because of the
substantive but reversible cognitive side effects associated with the use of anticonvulsants.

● Adjunctive therapy – In addition to the first- or second-line therapies described above, we suggest a
trial in children of adjunctive treatment with coenzyme Q10 and/or L-carnitine and riboflavin for at
least four months. All of these supplements are also used for mitochondrial disorders in children [9].
In some milder cases of CVS, these supplements may be effective as monotherapy rather than as
adjuncts to other medications. Anecdotally, some children with limited physical stamina or chronic
fatigue experience marked improvement on mitochondrial supplements. Sometimes, improved
stamina is recognized only in hindsight.

Retrospective studies support the efficacy of coenzyme Q10, L-carnitine, and riboflavin in children
with CVS [33-35,81]. In one report based on surveys of parents, the response to coenzyme Q10 alone
appeared similar to that of amitriptyline [33]. In another retrospective study of 30 patients treated
with a protocol consisting of fasting avoidance, coenzyme Q10 and L-carnitine supplementation, and,
in refractory cases, amitriptyline or cyproheptadine, 90 percent achieved at least a 50 percent
reduction in vomiting episodes [34].

For coenzyme Q10, a common starting dose is 10 mg/kg per day or 200 mg twice daily and target
blood levels are >3 to 4 microgram/mL. If blood levels of coenzyme Q10 are low, this may be the
result of poor bioavailability and indicate the need for a higher dose or different preparation.
Alternatively or in addition, L-carnitine can be used. A typical starting dose for L-carnitine is 50 or 100
mg/kg per day or 1 g twice daily. Many children require higher doses, and suggested target blood
level is a free carnitine level >40 micromol/L [34]. If there is no apparent therapeutic benefit during a
trial of at least four months, the supplements may be discontinued. Some patients may respond to
the addition of L-carnitine, riboflavin, and other agents such as alpha-lipoic acid and creatine. The
suggested dosing for riboflavin is 10 mg/kg per day divided into two daily doses [81]. These
supplements are available without prescription. There are some combination powdered preparations
that are easier for children to take and avoid the burden of multiple supplement pills (eg, Spectrum
Needs brand).

● Stopping treatment – In children, CVS tends to persist for three to five years [1,59]. CVS often
begins to improve around age 10 years and resolves by 18 years in approximately 75 percent of
individuals, although the vomiting symptoms are often replaced by migraine headaches [55,59] (see
'Natural history' above). Therefore, we typically attempt weaning off of prophylactic medication for
 adolescents who have had no episodes for one to two years or done well with few episodes for three
years. For practical reasons, we tend to wean the medication during the summer holidays when
school is in recess.

Adults — The approach to prophylactic therapy in adults is similar to that in older children, with slight
differences in priorities ( table 4C and algorithm 2):

● First-line – For adults who require prophylactic therapy for CVS, the first-line choice is amitriptyline,
using doses of 75 to 100 mg per day [2,24,74,85]. Amitriptyline is more likely to be effective for
patients with a personal or family history of migraines but also appears to be effective in those
without such a history. A typical approach is to initiate a low dose of 10 to 25 mg at night and, if well
tolerated, titrate upward based upon tolerance [88]. Its use may be limited by side effects such as
fatigue or sedation, confusion, headache, poor concentration, weight gain, constipation,
palpitations, and lightheadedness, which are common and may be dose-limiting. If these occur and
are intolerable, treatment may be switched to alternative tricyclic antidepressants (nortriptyline,
doxepin) [10,74,85]. For some individuals, higher doses may be needed to control the CVS, but this
should be approached with caution. (See 'Nonresponders' below.)

This recommendation is based on evidence from open-label and retrospective studies. In a review of
14 studies that included 600 adult and pediatric patients with CVS treated with amitriptyline or other
tricyclic antidepressants, 70 percent reported complete or partial improvement with a decrease in
frequency, duration, or severity of CVS symptoms [10]. Similarly, in an open-label study of 46 patients
followed for two years, treatment with a tricyclic antidepressant was associated with marked
reductions in the number of CVS episodes (from 17 to 3), duration of a CVS episode (from six to two
days), and in the number of emergency department visits/hospitalizations (from 15 to 3) [85].

● Second–line – When tricyclic antidepressants fail to control attacks or are not tolerated, the
anticonvulsants topiramate (100 mg), zonisamide (400 mg), and levetiracetam (1000 mg) may be
used [2,10,89]. Potential adverse effects of topiramate include cognitive dysfunction (8 to 12 percent
at migraine dosages), paresthesia, headache, fatigue, dizziness, mood problems, and loss of appetite
[90,91]. Alternatively, it is reasonable to do a trial of aprepitant 125 mg twice a week, as suggested in
guidelines based largely on the collective clinical experience of the panel [10]. There is minimal
experience to support or refute the use of propranolol for prophylaxis of CVS in adults, although
indirect evidence from its use for migraines suggests that it might be effective for CVS. Further
details on these drugs are discussed in separate topic reviews. (See "Preventive treatment of episodic
migraine in adults" and "Antiseizure medications: Mechanism of action, pharmacology, and adverse
effects", section on 'Zonisamide' and "Antiseizure medications: Mechanism of action, pharmacology,
and adverse effects", section on 'Levetiracetam'.)

● Adjunctive therapy – Mitochondrial supplements (coenzyme Q10, sometimes with riboflavin) are
sometimes used as adjuncts to other prophylactic agents in adults and are discussed as options in
the adult guideline [10]. This is based primarily upon indirect and very limited evidence for efficacy in
prophylaxis of migraines in adults and prophylaxis of CVS in children. (See 'Children and adolescents'
above and "Preventive treatment of episodic migraine in adults".)

Doses for adults are:

• Coenzyme Q10 – 200 mg orally twice daily

 • Riboflavin – 200 mg orally twice daily

Catamenial cyclic vomiting syndrome — For adolescent or adult women with catamenial CVS (ie,
when onset of episodes coincide with the onset of menses), addition or adjustment of hormonal
contraceptives is an early consideration. Options include oral contraceptives (with either low doses of
estrogen or progesterone-only) or intramuscular medroxyprogesterone acetate every three months. In
contrast, oral contraceptives with high doses of estrogen can also exacerbate symptoms in CVS patients
[9,92]. The strategy is similar to that used for estrogen-associated migraine. (See "Estrogen-associated
migraine, including menstrual migraine".)

Nonresponders — In children, adolescents, and adults who remain refractory to the therapies
recommended above, we suggest the following approach [55]:

● First, reevaluate for the possibility of a recurring trigger such as school (eg, bully), work, or family
stressors (eg, divorce). In children, an indolent infection such as chronic sinusitis can be a hidden
trigger. In adults, chronic unrevealed use of cannabis or reliance on opioids for pain management
may be triggers. (See 'Lifestyle interventions' above.)

● Second, in children, consider alternative causes of vomiting and evaluate for acute hydronephrosis
or small bowel obstruction (volvulus) during the vomiting episode screening with an abdominal
ultrasound or abdominal computed tomography (CT). Some adolescents may evolve from CVS into a
postprandial pattern of rumination or "coalescent" daily morning nausea. Adolescents and adults
should avoid cannabis and opioids. Adults may benefit from an evaluation for gastroparesis. (See
'Exclusion of other causes of vomiting' above.)

● Third, revisit the possibility of treatment with amitriptyline, with further dose escalation (>1.5 mg/kg
dose) using careful titration, ECG monitoring, and therapeutic monitoring. In some children or
adults, these high doses may be needed to control the CVS, especially if the individual is a rapid
metabolizer. These patients may not respond to standard doses of amitriptyline (1 to 1.5 mg/kg per
day) and have very low or undetectable blood levels of amitriptyline but may respond when the
amitriptyline dose is further increased and blood levels reach therapeutic levels of 100 to 150
micrograms/L [34]. As a general rule, an ECG and blood amitriptyline level should be obtained before
attempting to exceed 1.5 mg/kg per day. To avoid cardiotoxicity (tachyarrhythmia), the QTc interval
should be maintained below a safe threshold (eg, <460 msec for children and adolescents [93], <470
msec for women, and <450 msec for men [10]).

● Finally, combination medical therapy may be effective, such as [55,94]:

• Amitriptyline and an anticonvulsant (eg, topiramate)

• Amitriptyline and aprepitant
• Amitriptyline and propranolol
• Propranolol and erythromycin

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around the
world are provided separately. (See "Society guideline links: Nausea and vomiting".)
ADDITIONAL RESOURCES FOR PATIENTS

Support and counseling may be helpful for selected patients. The Cyclic Vomiting Syndrome Association
(CVSA), an international organization, was established in 1993 to provide support to patients with CVS.
This and other resources that may be useful for patients are listed in the table ( table 5).

INFORMATION FOR PATIENTS

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Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are
written at the 10th to 12th grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail
these topics to your patients. (You can also locate patient education articles on a variety of subjects by
searching on "patient info" and the keyword(s) of interest.)

● Basics topic (See "Patient education: Nausea and vomiting in adults (The Basics)".)

● Beyond the Basics topic (see "Patient education: Nausea and vomiting in infants and children
(Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Cyclic vomiting syndrome (CVS) is an idiopathic disorder characterized by recurrent, stereotypical

bouts of vomiting with intervening periods of normal or baseline health. Both children and adults are
affected, although the clinical presentation and natural history vary with age. Adults with CVS may
develop symptoms beginning either in childhood or adulthood. (See 'Introduction' above.)

● The pathogenesis of CVS remains unknown, and CVS may represent a heterogeneous group of
disorders. An association between CVS and migraine headaches has been consistently described in
the majority of patients, suggesting that there may be a common pathophysiologic process.
However, CVS has also been linked to autonomic dysfunction, hypothalamic-pituitary-adrenal axis
hyperreactivity, mitochondrial disorders, estrogen sensitivity (catamenial CVS), food allergy, and
possibly chronic high-dose cannabis use. (See 'Pathogenesis' above.)

● Diagnostic criteria have been proposed based upon consensus of experts by the North American
Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) for children (
algorithm 1) and Rome IV Committees for children and adults. The specific pattern, severity, and
duration of vomiting episodes varies among patients but is usually stereotypical for an individual
patient. CVS is diagnosed based primarily upon the history and exclusion of alternative diagnoses (
table 3). (See 'Diagnosis' above.)
● Management of CVS includes addressing lifestyle modifications and comorbidities, especially anxiety.
Specific interventions depend on age of patient, severity of symptoms, timing of presentation, and
setting. Our general approach is as follows (see 'Lifestyle interventions' above and 'Management'
above):

• Prodromal and early symptoms (home management) – For patients with an episode of CVS
that can be identified during the prodrome or shortly after the vomiting begins, we suggest
treatment with an abortive agent such as intranasal or subcutaneous sumatriptan or oral
aprepitant (Grade 2C). The choice between these options is based largely on patient and
provider preference ( table 4B). Aprepitant is particularly appropriate for patients without a
personal or family history of migraine and those who have failed to respond to triptans. Abortive
treatments are most effective if they are given early in the prodrome and should be prescribed
to have at home for timely use by the patient. Some patients may have sufficient response to
abortive therapy to obviate the need for additional intervention. (See 'Abortive medications'
above.)

• Acute vomiting episodes (emergency department management) – For patients who present
to the emergency department with moderate to severe vomiting episodes, supportive care
includes the following ( table 4B) (see 'Supportive care' above):

- Intravenous hydration – Intravenous fluids should be given to replace fluid losses.

Hypovolemia is initially corrected with fluid boluses (eg, 10 to 20 mL/kg of isotonic saline).
For ongoing maintenance fluid therapy in children, we suggest a half-normal saline (0.45%
sodium chloride) with 10% dextrose rather than lower dextrose concentrations (Grade 2C).
For adults, we typically use isotonic saline (0.9% sodium chloride) with 5% dextrose. This
dextrose infusion may lessen the catabolic state and ketosis induced by the acute CVS
episode, which can prolong vomiting.

- Antiemetic therapy – For patients presenting with acute vomiting episodes, we suggest
initial treatment with high-dose 5-hydroxytryptamine (5-HT3) receptor antagonist (eg,
ondansetron, granisetron) (Grade 2C). In addition, we suggest concomitant treatment with
an agent with both antiemetic and sedating effects (eg, diphenhydramine or lorazepam)
(Grade 2C). The sedating agent provides additional symptom relief, which is valuable
because control of nausea and vomiting is often incomplete with 5-HT3 receptor antagonist
therapy.

Triptan therapy (eg, sumatriptan) may be useful if the patient presents to the emergency
department in the very early phases of the episode (ie, within one hour of the onset of
vomiting), but this is rarely the case. (See 'Abortive medications' above.)

- Environmental measures – Whenever possible, the patient should be kept in a dark, quiet,
low-stimulation environment because any disturbance of the hyperesthetic patient typically
incites more nausea and vomiting.

- Treatment of pain (if present) - Management of abdominal and headache pain usually
begins with an intravenous nonsteroidal antiinflammatory drug (eg, ketorolac). If the pain
has a midepigastric or dyspeptic quality, an antireflux medication (eg, histamine type 2
receptor antagonist or proton pump inhibitor) is a reasonable adjunctive therapy. Narcotics
 are reserved for severe and refractory pain since they can worsen vomiting and induce
dependence over time.

• Prophylactic therapy – For patients who experience CVS episodes that are frequent, prolonged,
or debilitating, or that result in recurrent emergency department or hospital admissions, we
suggest prophylactic therapy (Grade 2C). The limited evidence for the use of these medications
for CVS suggests similar levels of efficacy, so selection among these medications is based
primarily upon side effects and toxicities, as well as differences in the amount of clinical
experience with use of each drug for CVS within each age group. (See 'Prophylactic medications'
above.)

- For children <5 years, we suggest prophylactic treatment with cyproheptadine or pizotifen
rather than other agents (Grade 2C). This preference is based primarily on a more favorable
side effect profile in younger children and is supported by an expert panel. Potential side
effects of cyproheptadine include weight gain and sedation.

- For children ≥5 years and adults, we (and an expert panel) suggest amitriptyline or other
tricyclic antidepressant (Grade 2C). This preference is based upon the greater clinical
experience with amitriptyline for CVS compared with alternative agents (aprepitant,
topiramate) and overall higher level of effectiveness, despite frequent but tolerable side
effects.

Alternatives include aprepitant, propranolol (typically used only for children), or selected
anticonvulsants. Dosing, side effects, and alternatives are outlined in the table ( table 4C). In
addition, for most children who warrant prophylaxis, we suggest a trial of concomitant
treatment with coenzyme Q10, with or without L-carnitine and riboflavin supplementation
(Grade 2C). Coenzyme Q10, sometimes with riboflavin, is sometimes used as an adjunct to other
prophylactic agents in adults, based upon indirect and very limited evidence for efficacy in
prophylaxis of migraines. (See 'Children and adolescents' above and 'Adults' above.)

ACKNOWLEDGMENT

The editorial staff at UpToDate would like to acknowledge Emily Dulude, MD, Richard G Boles, MD, and
David J Desilets, MD, PhD, who contributed to an earlier version of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

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Topic 2588 Version 41.0
GRAPHICS

Comparison of overlapping symptoms in cyclic vomiting syndrome, abdominal migraine, and migraine
headaches in children and adolescents

Percentage of patients with symptom

 
Cyclic vomiting syndrome Abdominal migraine Migraine headache

Core symptoms

Vomiting 100 39 to 72 40 to 69

Abdominal pain 3 to 81 100 10 to 55

Headache 38 to 59 31 to 50 100

Associated symptoms

Lethargy 91    

Pallor 87 90 to 100 23 to 88

Anorexia 74 91 to 98 13 to 93

Nausea 72 73 to 91 46 to 100

Photophobia 32 1 to 42 27 to 81
[1]
Mean age

   5 years 9 years 11 years

Reference: 
1. Abu-Arafeh I, Russell G. Cyclical vomiting syndrome in children: a population-based study. J Pediatr Gastroenterol Nutr 1995; 21:454.
Adapted from: Li BU, Balint JP. Cyclic vomiting syndrome: Evolution in understanding of a brain-gut disorder. Adv Pediatr 2000; 47:117.

Graphic 80667 Version 7.0

Clinical and epidemiological features of cyclic vomiting syndrome

Feature Characterization

Female:male ratio 55:45

Mean age of 5.3 years in children, 35 years in adults

onset

Morbidity 20 days of missed school per year; 50% of patients require intravenous hydration

Symptoms:
Vomiting 6 to 8 times/hour at peak, often with bile and blood
Autonomic Lethargy, pallor; sometimes with fever or copious salivation
Gastrointestinal Abdominal pain, retching, anorexia, nausea; sometimes diarrhea
Neurologic Migraine-like symptoms in approximately one-third of patients, including headache, photophobia, phonophobia, or vertigo  

Behavioral  Use of hot-water showers or bathing to attenuate nausea (similar to cannabis hyperemesis syndrome, but also occurs in children and
>50% of adult CVS patients without exposure to cannabis)
Rapid drinking of fluids before onset of vomiting due to bitterness of bile

Temporal pattern Most patients have a stereotypical pattern; most episodes occur at night or early morning

  Children (or adults with pediatric-onset CVS):

Mean duration 2 days

Mean 12 cycles/year
Triggering events identified in 70% of patients; includes infection (40%), psychological stress (35%), dietary (25%)*,
menstrual (10%), cannabis withdrawal
Interepisodic nausea rare (12%)

Adult-onset CVS:

Mean duration 6 days

Mean 4 cycles/year
Triggering events are similar to those in children but may be less common
Interepisodic nausea common (40 to 60%)

Association with Children – Approximately 30% of patients progress to migraine headaches by early adolescence, and 75% progress to
migraines migraines by 18 years
Adults – Approximately 50% have migraine headaches 

Family history of Present in 40 to 80% of children and 25 to 70% of adults

migraine

CVS: cyclic vomiting syndrome.

* Commonly reported food triggers include chocolate, cheese, and monosodium glutamate. A causal association has not been established.

Adapted from: 
1. Li BU, Balint JP. Cyclic vomiting syndrome: Evolution in understanding of a brain-gut disorder. Adv Pediatr 2000; 47:117.
2. Li BU. Cyclic vomiting: New understanding of an old disorder. Contemp Pediatr 1996; 17:48.
3. Abell TL, Adams KA, Boles RG, et al. Cyclic vomiting syndrome in adults. Neurogastroenterol Motil 2008; 20:269.
4. Kumar N, Bashar Q, Reddy N, et al. Cyclic Vomiting Syndrome (CVS): is there a difference based on onset of symptoms--pediatric versus adult? BMC
Gastroenterol 2012; 12:52.

Graphic 62483 Version 6.0

Differences between cyclic and chronic temporal patterns of
vomiting

Differences between cyclic and chronic temporal patterns of vomiting can be

compared when the number of emeses is plotted over a 2-month period. The chronic
pattern (red line) is characterized by low-grade, nearly daily episodes, whereas the
cyclic pattern (black line) is marked by high-intensity episodes every several weeks.

Adapted from: Li BU. New hope for children with cyclic vomiting syndrome. Contemp Pediatr 2002;
19:121.

Graphic 54863 Version 4.0

Differential diagnosis of cyclic vomiting syndrome [1-3]

Medications and toxic Disorders of the gut and Endocrinologic and

Neurologic causes
etiologies peritoneum metabolic causes

Cancer chemotherapy Mechanical obstruction Migraine and variants* Inborn errors of

Analgesics (eg, aspirin, Gastric outlet obstruction Migraine metabolism (primarily
NSAIDs, narcotics) Malrotation with intermittent headache* infants and toddlers)*
Cardiovascular volvulus* Abdominal Organic acidemias,
medications and Superior mesenteric artery migraine* urea cycle defects,
diuretics syndrome Increased intracranial fatty acid oxidation
Hormonal therapies pressure disorders
Median arcuate ligament
(oral antidiabetic syndrome Hydrocephalus Uremia
agents, contraceptives) Duodenal atresia, web, or (primarily infants Diabetic ketoacidosis*
Antibiotics/antivirals diverticulum and toddlers)* Hyperparathyroidism,
Erythromycin Other causes of small bowel Chiari type I hypoparathyroidism
Tetracycline obstruction malformation* Hyperthyroidism
Sulfonamides Functional gastrointestinal disorders Malignancy (eg, Adrenal insufficiency
Antituberculous Nonulcer dyspepsia brainstem tumors) Acute intermittent
drugs Functional vomiting* Stroke porphyria
Acyclovir Dysmotility Infection
CNS-active drugs (eg, Gastroparesis* Congenital
antiparkinsonian drugs, malformation
Chronic intestinal pseudo-
anticonvulsants) Pseudotumor Gynecologic or urologic
obstruction
Antiasthmatics cerebri disorders
Peptic and inflammatory
Radiation therapy Seizure disorder
Peptic ulcer disease* Pregnancy
Jamaican vomiting Demyelinating
Eosinophilic esophagitis* Urolithiasis
sickness (unripe ackee disorders
Crohn disease Ovarian cyst
fruit) Emotional responses
Recurrent subacute appendicitis Premenstrual syndrome
Drug misuse and abuse (eg, pain)
Inflammatory intraperitoneal Uteropelvic junction
Cannabinoid Psychiatric disease
disease obstruction*
hyperemesis Functional
Visceral
syndrome vomiting
Cholecystitis*/cholelithiasis/biliary
Ethanol abuse Anxiety disorders Miscellaneous causes
dyskinesia
Nicotine use Depression
Choledochal cysts
Hypervitaminosis A Anorexia nervosa Postoperative nausea
Pancreatitis* and vomiting*
Apomorphine Bulimia nervosa
Hepatitis Cardiac disease
poisoning (medical Labyrinthine disorders
child abuse) Gastrointestinal infections* Myocardial infarction
Benign paroxysmal
Pinworms, Blastocystis hominis, Heart failure
positional vertigo
Entamoeba histolytica, Giardia,
Motion sickness Radiofrequency
Gastrospirillum
Labyrinthitis ablation ¶
Miscellaneous
Menière disease Postural orthostatic
Mesenteric ischemia tachycardia syndrome
Iatrogenic
Retroperitoneal fibrosis (POTS)*
Fluorescein
Starvation
angiography
Chronic sinusitis*

NSAIDs: nonsteroidal antiinflammatory drugs; CNS: central nervous system.

* Indicates disorders that are more common considerations for children. [1]
¶ Vomiting after radiofrequency ablation is very common but may be anesthesia-related. [2,3]

References:
1. Li BU, Murray RD, Heitlinger LA, et al. Heterogeneity of diagnoses presenting as cyclic vomiting. Pediatrics 1998; 102:583.
2. Tyndall A, Nyström KV, Funk M. Nausea and vomiting in patients undergoing radiofrequency catheter ablation. Am J Crit Care 1997; 6:437.
3. Erb TO, Hall JM, Ing RJ, et al. Postoperative nausea and vomiting in children and adolescents undergoing radiofrequency catheter ablation: a
randomized comparison of propofol- and isoflurane-based anesthetics. Anesth Analg 2002; 95:1577.
Original table modified for this publication. From: Quigley EMM, Hasler WL, Parkman HP. AGA technical review on nausea and vomiting. Gastroenterology 2001;
120:263. Table used with the permission of Elsevier Inc. All rights reserved.

Graphic 57659 Version 7.0

Evaluation of cyclic vomiting pattern in children older than 2 years

CVS: cyclic vomiting syndrome; NA: sodium; K: potassium; Cl: chlorine; HCO 3 : serum bicarbonate; BUN: blood urea nitrogen; UGI: upper gastrointestinal;
ALT: alanine aminotransferase; GGT: gamma-glutamyl transpeptidase; IV: intravenous; MRI: magnetic resonance imaging.
* Another set of criteria was developed by the Rome foundation in 2016 (Rome IV criteria), which has higher sensitivity and lower specificity compared with
the NASPGHAN criteria [1].
¶ May not need metabolic evaluation.
Δ Bilious vomiting is reasonably common in CVS. Surgical consultation is appropriate if the patient has additional radiographic or physical signs of intestinal
obstruction.

Reference:
1. Hyams JS, Di Lorenzo C, Saps M, et al. Functional Disorders: Children and Adolescents. Gastroenterology 2016.
Reproduced with permission from: Li BU, Lefevre F, Chelimsky GG, et al. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus
statement on the diagnosis and management of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr 2008; 47:379. Copyright © 2008 Lippincott Williams &
Wilkins.

Graphic 53337 Version 10.0

Lifestyle changes in cyclic vomiting syndrome

Lifestyle changes (for 1 to 2 months or 1 to 2 cycles)

Reassurance and anticipatory guidance (eg, episodes are not self-induced and natural history)

Avoidance of triggers

Keep a "vomiting diary" to document potential precipitating factors

Avoid fasting

Recognize the potential role of excitement as a trigger (eg, downplay big events)

Maintain good sleep hygiene (eg, avoid sleep deprivation)

Avoid triggering foods: chocolate, cheese, monosodium glutamate, antigenic foods

Avoid excessive energy output

Supplemental carbohydrate for fasting-induced episodes

Provide fruit juices or other sugar-containing drinks

Provide extra snacks between meals, before exertion, or at bedtime

Migraine headache lifestyle interventions

Regular aerobic exercise (avoid overexercising)

Regular meal schedules (ie, avoid skipping meals)

Moderation in consuming or avoidance of caffeine

Reproduced with permission from: Li BU, Lefevre F, Chelimsky GG, et al. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
consensus statement on the diagnosis and management of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr 2008; 47:379. Copyright © 2008 Lippincott
Williams & Wilkins.

Graphic 77478 Version 11.0

Supportive and abortive treatment approaches for cyclic vomiting syndrome

Supportive care
Fluid, electrolyte, and nutritional management

Initial bolus: Administer isotonic saline (0.9% sodium chloride), 10 to 20 mg/kg (or 1 L for adults) as needed for hypovolemia.
Subsequent fluids:

Children – 10% dextrose, 0.45% sodium chloride solution with potassium chloride as appropriate.
Adults – 5% dextrose, 0.9% sodium chloride solution with potassium chloride as appropriate.
 
Infuse the above fluids at 1.5 times the maintenance fluid rate. Alternatively, 10% or 5% dextrose in water can be infused at 1 times the
maintenance fluid rate, along with a separate 0.9% sodium chloride solution at 0.5 times the maintenance fluid rate, using a Y-connector.
Monitor urine output carefully because some patients develop SIADH and may require fluid restriction.

If no enteral intake for 3 to 5 days, initiate peripheral parenteral nutrition with 1.5 g of amino acids/kg/day and energy units above the
catabolic threshold of 55 to 70 kcal/kg/day.

Antiemetic agents

Ondansetron (5-HT 3 receptor antagonist)

Dosing:
Children – 0.3 mg/kg/dose intravenously, up to a maximum of 16 mg for the initial dose. May give an additional dose (maximum
8 mg) every 4 to 6 hours; do not exceed 32 mg/24 hours.
Adults – 8 mg intravenously; a 16 mg/dose may be used for the first dose for selected patients <75 years old with no risk factors
for QT c prolongation. May give an additional 8 mg dose every 4 to 6 hours; do not exceed 32 mg/24 hours. [1]

Side effects – Headache, constipation, prolonged QT c interval.

Sedating agents

Diphenhydramine (antihistamine)*

Dosing:
Children – 1 to 1.25 mg/kg/dose intravenously every 6 hours (up to a maximum of 50 mg per dose).
Adults – 25 to 50 mg intravenously. May repeat every 6 hours (maximum of 400 mg per day).

Side effects – Drowsiness, dry mouth, paradoxical excitement or irritability in young children.

Lorazepam (benzodiazepine)*

Dosing:
Children – 0.05 to 0.1 mg/kg/dose intravenously every 6 hours (up to a maximum of 2 mg per dose).
Adults – 1 to 2 mg intravenously. May repeat every 6 hours.

Side effects – Respiratory depression, dizziness, hallucinations, sedation, paradoxical excitement or irritability in young children.

Analgesic agents

Ketorolac (nonsteroidal antiinflammatory drug)

Dosing:
Children – 0.5 mg/kg intravenously every 6 to 8 hours, for 48 hours (up to a maximum of 30 mg per dose). Do not exceed a
maximum daily dose of 120 mg.
Adults ≥50 kg – 30 mg intravenously. May repeat every 6 hours (maximum of 120 mg per day).

Side effects – Gastrointestinal hemorrhage, hypersensitivity.

Contraindications – Avoid in patients with dehydration or renal insufficiency (can cause acute kidney injury in dehydrated patients).

Alternatives – Narcotics, intravenous morphine or hydromorphone by bolus or by patient-control infusion.

Treatment of specific signs and symptoms

Epigastric pain – Acid suppression by H 2 RAs or PPIs, (eg, intravenous famotidine, pantoprazole).

Diarrhea – Antidiarrheals (eg, loperamide).

Hypertension (if persistent and severe) – Short-acting ACE inhibitors (eg, enalapril) or beta-2 adrenergic blockers (eg, labetalol).

Treatment of specific complications

Dehydration and electrolyte deficit – Replace calculated deficits.

Metabolic acidosis – Determine cause and treat accordingly.

SIADH – Restrict free water intake.

Hematemesis – Intravenous H 2 RAs or PPIs.

Weight loss – Nasogastric or parenteral nutrition.

Abortive care
Sumatriptan ¶ (serotonin agonist)
 Start as soon as possible during the prodrome or within 1 hour of the onset of vomiting.

Dosing:
Age 5 to 11 years, or weight 20 to 39 kg – Intranasal dose 5 to 10 mg or subcutaneous dose 2 to 3 mg (by self-injection). Δ
Age 12 to 17 years, or weight 40 to 59 kg – Intranasal dose 10 to 20 mg or subcutaneous dose 3 to 6 mg. Δ
Age ≥18 years, or weight ≥60 kg – Intranasal dose 20 mg or subcutaneous dose 6 mg. If there is no response or partial response to
the first dose, the dose may be repeated after 2 hours for intranasal administration, or 1 hour for subcutaneous administration.
Maximum of 6 doses per week. [1]

Side effects – Neck pain/burning, tingling, numbness, dizziness.

Contraindications – Basilar artery migraine. Do not use in patients with underlying coronary artery disease, peripheral vascular disease,
hypertension, or stroke.

Alternatives – Zolmitriptan (intranasal) ◊

Aprepitant § [1,2] (neurokinin 1 receptor antagonist)

Administer during the prodrome (at least 30 minutes before onset of vomiting) and on days 2 and 3.

Dosing:
<15 kg body weight – 80 mg orally on day 1, then 40 mg on days 2 and 3.
≥15 to 20 kg body weight – 80 mg orally on day 1, then 80 mg on days 2 and 3.
>20 kg body weight and adults – 125 mg orally on day 1, then 80 mg on days 2 and 3.

Alternatives – Early administration of ondansetron may reduce the pace and amount of vomiting (refer to antiemetic agents above for
dosing).

Recovery and refeeding

Feed ad libitum when child declares episode is over.

SIADH: syndrome of inappropriate antidiuretic hormone; 5-HT 3 : 5-hydroxytryptamine; H 2 RAs: histamine-2 receptor antagonists; PPIs: proton pump
inhibitors; ACE: angiotensin-converting enzyme.
* For sedation of pediatric patients, we typically begin with diphenhydramine and switch to lorazepam if sedation is not adequate. Adult guidelines
suggest initiating treatment with lorazepam.
¶ Sumatriptan dosing is not well established, especially for young children. These doses are based on the authors' clinical experience, a few published
case series [3,4 ], and extrapolation from doses used for treatment of migraines in children. In children with both migraines and cyclic vomiting, the
vomiting symptoms sometimes respond to sumatriptan at lower doses compared with those needed to treat the migraines.
Δ For children 5 to 12 years of age, sumatriptan should be initiated at the lower dose initially, with a repeat dose in 2 hours for intranasal
administration and 1 hour for subcutaneous administration. If this dose achieves an inadequate response and the patient has no adverse effects, then
subsequent next treatment should be at the higher dose. For children age 12 to 18 years, the same approach should be used except for those who
have entered puberty (ie, exhibiting secondary sexual characteristics), in which case, the higher dose may be used first. Some clinicians also use
sumatriptan for children 3 to 5 years at lower doses (eg, 1 mg subcutaneously) [3 ].
◊ Suggested intranasal dosing for zolmitriptan is 2.5 mg for age 5 to 12 years, 2.5 to 5 mg for 12 to 18 years, and 5 mg for ≥18 years [5-7].
§ Aprepitant also may be used as a prophylactic therapy, given twice weekly (refer to UpToDate content and table on prophylactic therapy for cyclic
vomiting syndrome) [1,2].

References:
1. Venkatesan T, Levinthal DJ, Tarbell SE et al. Guidelines on Management of Cyclic Vomiting Syndrome in Adults by the American Neurogastroenterology
and Motility Society and the Cyclic Vomiting Syndrome Association. Neurogastroenterol Motil 2019; Suppl 2:e13604.
2. Cristofori F, Thapar N, Saliakellis E, et al. Efficacy of the neurokinin-1 receptor antagonist aprepitant in children with cyclical vomiting syndrome.
Aliment Pharmacol Ther 2014; 40:309.
3. Hikita T, Kodama H, Kaneko S, et al. Sumatriptan as a treatment for cyclic vomiting syndrome: a clinical trial. Cephalalgia 2011; 31:504.
4. Duquesnoy C, Mamet JP, Sumner D, Fuseau E. Comparative clinical pharmacokinetics of single doses of sumatriptan following subcutaneous, oral, rectal
and intranasal administration. Eur J Pharmaceut Sci 1998; 6:99.
5. Zhou W, Li J, Birmingham B, Xu H, Lillieborg S, Zhou D, Al-Huniti N. Population pharmacokineteic analysis of zolmitriptan and its metabolite in adults
and adolescents to support dose selection in children with migraine. J Clin Pharmacol 2017; 57:1258.
6. McKeage K. Zolmitriptan nasal spray: a review in acute migraine in pediatric patients 12 years of age or older. Pediatr Drugs 2016; 18:75.
7. FG Freitag, Director of Headache Medicine, Medical College of Wisconsin, Personal communication, 2019.
Adapted from: Li BU, Lefevre F, Chelimsky GG, et al. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus statement on
the diagnosis and management of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr 2008; 47:379.

Graphic 78562 Version 20.0

Prophylactic or preventive medications* in cyclic vomiting syndrome

Children 2 to 5 years old

Antihistamines – Cyproheptadine (first choice)

Dosing – 0.25 to 0.5 mg/kg/day orally divided into 2 or 3 daily doses, or given once daily at night to reduce daytime sedation (maximum of
12 mg per 24 hours). Available in 4 mg tablets and a 2 mg/5 mL syrup.

Side effects – Increased appetite, weight gain, sedation, dry mouth, constipation, urinary retention; may also cause paradoxical excitation
in young children.

Alternatives – Pizotifen (available in United Kingdom and Canada).

Beta blockers – Propranolol (second choice)

Dosing – 0.25 to 1 mg/kg/day orally divided into 2 or 3 daily doses, most often 10 mg 2 or 3 times daily. Initiate at 0.25 mg/kg/day and
increase every 1 to 4 weeks in increments of 5 or 10 mg as needed and tolerated. Maximum daily dose: 120 mg/day. Available in tablet
and liquid forms in various strengths and concentrations.

Monitoring – Monitor and maintain resting heart rate ≥60 bpm.

Side effects – Lethargy, reduced exercise tolerance, hypoglycemia, bradycardia, bronchospasm, hypotension, night terrors.

Contraindications – Asthma, diabetes, heart disease.

Discontinuation – Do not stop abruptly, must be tapered over 1 to 2 weeks.

Children older than 5 years and adults

Tricyclic antidepressants – Amitriptyline (first choice)

Dosing:
Children – Initiate at 0.25 to 0.5 mg/kg/day orally at bedtime, may gradually increase dose based on response and tolerability in
weekly increments up to 1 to 1.5 mg/kg/day. For dose >1 mg/kg/day, may administer at bedtime or divide twice daily.
Adults – Initiate at 10 to 25 mg orally at night. May increase in increments of 5 to 10 mg as needed and tolerated at weekly intervals.
The mean effective dose for adults is 75 to 100 mg daily [1].

Monitoring – Check ECG QTc interval before starting, during titration and after the target dose is reached. QTc interval should be
maintained <460 msec for children, <470 msec for adult women, and <450 msec in adult men [1].

Side effects – Constipation, sedation, weight gain, dry mouth, arrhythmia, behavioral changes (especially in young children).

Discontinuation – Gradually taper dose to minimize the incidence of withdrawal.

Alternatives – Nortriptyline ¶ (available in 10 mg/5 mL liquid).

Beta blockers – Propranolol (second choice for children; not generally used for cyclic vomiting syndrome in adults) – Refer to section
on younger children above for dosing

Formulation consideration – For adolescents, may use the extended-release form of propranolol (for once-daily dosing), after titration to a
minimum daily dose of 60 mg.

NK1 receptor antagonist – Aprepitant [1,2]

Dosing for prophylaxis Δ:

For <40 kg body weight – 40 mg orally twice weekly.
For 40 to 60 kg body weight – 80 mg orally twice weekly.
For >60 kg body weight – 125 mg orally twice weekly.

Side effects – Hiccups, lethargy/fatigue, headache.

Drug-drug interactions – Significant inhibitors and inducers of CYP3A4 increase and decrease levels of aprepitant, respectively, and should
be avoided if possible.

Other agents – For children older than 5 years and adults

Anticonvulsants – Phenobarbital ¶ (used primarily for children)

Dosing – 2 mg/kg/day orally, administered at bedtime. Maximum dose 80 mg per 24 hours.

Side effects – Sedation, cognitive impairment.

Alternative anticonvulsants

Topiramate

Dosing:
Children – 2 mg/kg/day divided in 2 daily doses. Titrate weekly as tolerated from a beginning dose of 15 or 25 mg once a day.
Consult a pediatric neurologist for drug selection and dose adjustment.
Adults – Initiate at 25 mg orally once a day. Titrate dose by 25 mg weekly as tolerated to a target dose of 100 mg daily.

Others – Levetiracetam and zonisamide (primarily in adults).

Supplements ¶ ◊ (used primarily in children, but also suggested as a consideration for adults [1])

Coenzyme Q 10

Dosing:
 Children – 10 mg/kg/day orally divided into 2 or 3 daily doses.
Adults – 200 mg orally 2 times daily.

Side effects: diarrhea.

L-carnitine

Dosing:
Children – 50 to 100 mg/kg/day orally divided into 2 or 3 daily doses.
Adults – 1 g orally 3 times daily.

Side effects: diarrhea, fishy body odor.

Riboflavin

Dosing:
Children – 10 mg/kg/day orally divided in 2 daily doses.
Adults – 200 mg orally 2 times daily.

ECG: electrocardiogram; NK1: neurokinin 1.

* All medication recommendations are made for off-label use.
¶ Limited or no published experience regarding efficacy.
Δ Aprepitant has also been used for abortive therapy. For abortive dosing, refer to UpToDate table on supportive and abortive therapy for cyclic
vomiting syndrome.
◊ For children with cyclic vomiting syndrome, UpToDate authors suggest a trial of adjunctive treatment with coenzyme Q 10 and/or L-carnitine and
riboflavin, in addition to the first- or second-line therapies described above.

References:
1. Venkatesan T, Levinthal DJ, Tarbell SE et al. Guidelines on Management of Cyclic Vomiting Syndrome in Adults by the American Neurogastroenterology
and Motility Society and the Cyclic Vomiting Syndrome Association. Neurogastroenterol Motil 2019; Suppl 2:e13604.
2. Cristofori F, Thapar N, Saliakellis E, et al. Efficacy of the neurokinin-1 receptor antagonist aprepitant in children with cyclical vomiting syndrome.
Aliment Pharmacol Ther 2014; 40:309.
Adapted from: Li BU, Lefevre F, Chelimsky GG, et al. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus statement on
the diagnosis and management of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr 2008; 47:379.

Graphic 68579 Version 14.0

Management of cyclic vomiting syndrome in adults

CVS: cyclic vomiting syndrome; ED: emergency department.

From: Venkatesan T, Levinthal DJ, Tarbell SE, et al. Guidelines on Management of Cyclic Vomiting Syndrome in
Adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association.
Neurogastroenterol Motil 2019; 31:e13604. https://onlinelibrary.wiley.com/doi/full/10.1111/nmo.13604. Copyright
© 2019 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd. Reproduced with
permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is
needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's
permissions department either via email: permissions@wiley.com or use the RightsLink service by clicking on the
'Request Permission' link accompanying this article on Wiley Online Library (https://onlinelibrary.wiley.com/).

Graphic 128378 Version 1.0

Family support and informational resources for cyclic vomiting syndrome

Cyclic Vomiting Syndrome Association (CVSA)

PO Box 270341, Milwaukee, WI 53227

Phone: 414-342-7880
Email: cvsaonline@gmail.com
www.cvsaonline.org

International Foundation for Gastrointestinal Disorders (IFFGD)

PO Box 170864, Milwaukee, WI 53217

Phone: 414-964-1799
For children: www.aboutKidsGI.org
For adults: www.iffgd.org

National Migraine Association (MAGNUM)

100 N Union St, Suite B, Alexandria, VA 22314

Phone: 703-349-1929
www.migraines.org

National Organization for Rare Disorders (NORD)

55 Kenosia Ave, Danbury, CT 06810

Phone: 203-744-0100
Fax: 203-263-9938
www.rarediseases.org

United Mitochondrial Disease Foundation (UMDF)

8085 Saltsburg Rd, Suite 201, Pittsburgh, PA 15239

Phone: 412-793-8077
Fax: 412-793-6477
Email: info@umdf.org
www.umdf.org

Adapted with permission from: Li BU, Lefevre F, Chelimsky GG, et al. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
consensus statement on the diagnosis and management of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr 2008; 47:379. Copyright © 2008 Lippincott
Williams & Wilkins. Contact information current as of February 2018.

Graphic 74868 Version 18.0

Contributor Disclosures
B UK Li, MD Consultant/Advisory Boards: Takeda, GLG Consulting [Antiemetics]. Nicholas J Talley, MD, PhD Equity
Ownership/Stock Options (Spouse): APA Group [Natural gas/electricity]. Patent Holder: Biomarkers of irritable bowel
syndrome [Irritable bowel syndrome]; Mayo Clinic [Dysphagia questionnaire]; Mayo Clinic [Bowel Disease
questionnaire]; Nestec [Irritable bowel syndrome]; Singapore Provisional Patent [BDNF Tissue Repair Pathway].
Grant/Research/Clinical Trial Support: Allakos [Gastric eosinophilic disease]. Consultant/Advisory Boards: Allakos
[Gastric eosinophilic disease]; Anatara Life Sciences, Brisbane [IBS/IBD]; ARENA Pharmaceuticals [Abdominal pain];
Aviro Health [Digestive health]; Bayer [Inflammatory bowel syndrome]; Cadila Pharmaceuticals [CME]; Censa
[Diabetic gastroparesis]; Danone [Probiotic]; Dr. Falk Pharma [Eosinophilia]; Glutagen [Celiac disease]; International
Foundation for Functional Gastrointestinal Disorders [Advisory board, functional GI disorders]; IsoThrive [Esophageal
microbiome]; Planet Innovation [Gas capsule, inflammatory bowel syndrome]; Progenity Inc. [Intestinal capsule];
Sanofi-Aventis [Probiotic]; Takeda [Gastroparesis]; twoXAR [Inflammatory bowel syndrome drugs]; Viscera Labs
[Inflammatory bowel syndrome, diarrhea]. Marc C Patterson, MD, FRACP Equity Ownership/Stock Options: IntraBio
[General lysosomal diseases and ataxic disorders]. Grant/Research/Clinical Trial Support: Orphazyme [Niemann-Pick
disease, type C]; Shire [Metachromatic leukodystrophy]; Amicus [Late-onset Pompe disease]; Glycomine [Congenital
disorders of glycosylation]. Consultant/Advisory Boards: Actelion [Niemann-Pick C]; Amicus [Fabry, Gaucher, Pompe];
Cerecor [Congenital disorders of glycosylation]; IntraBio [General lysosomal diseases and ataxic disorders]; Novartis
[Multiple sclerosis]; Orphazyme [Niemann-Pick disease, type C]; Shire [Metachromatic leukodystrophy]. Other
Financial Interest: Sage [Child neurology]; Wiley [JIMD]. Melvin B Heyman, MD, MPH Equity Ownership/Stock
Options: Amgen. Grant/Research/Clinical Trial Support: Jannsen, Genentech, AbbVie, Lilly, Takeda, and Shire [IBD];
Pfizer [Tofacitinib]. Consultant/Advisory Boards: Genentech and Certara [IBD]; Mahana [GI conditions]; Kate Farms
[Plant-based nutrition]. Alison G Hoppin, MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed
by vetting through a multi-level review process, and through requirements for references to be provided to support
the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of
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