Medication Summary
Medications used to prevent, ameliorate, or abort vomiting episodes include cyproheptadine, amitriptyline, topiramate, zonisamide, levetiracetam, propranolol, phenobarbital, erythromycin, ondansetron, promethazine, and prochlorperazine.
Antiemetic Agents
Class Summary
The vomiting center (VC) of the central nervous system (CNS) may be stimulated directly by gastrointestinal (GI) irritation, motion sickness, or vestibular neuritis. Increased activity of central neurotransmitters, such as dopamine in the chemoreceptor trigger zone (CTZ) or acetylcholine in the VC, appear to be major mediators of vomiting.
An emetogenic episode may initiate the release of serotonin (5-HT) from enterochromaffin cells in the GI tract. 5-HT then binds to 5-HT3 receptors, which stimulate vagal neurons that transmit signals to the VC, resulting in nausea and vomiting. Pharmacologic agents are directed to the particular etiology or mechanism that stimulates the vomiting response.
Ondansetron (Zofran)
The 5-HT3 antagonist ondansetron directly acts at the CTZ and vagal afferents from the GI tract. It attenuates or, occasionally, aborts an active episode of CVS. High doses are more effective in patients with CVS.
Promethazine (Phenergan, Phenadoz)
Promethazine is a phenothiazine derivative that possesses antihistaminic, sedative, antimotion sickness, antiemetic, and anticholinergic effects.
Prochlorperazine (Compro)
Prochlorperazine may relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through its anticholinergic effects and depressing the reticular activating system.
Antihistamines, 1st Generation
Class Summary
Antihistamines may be used to prevent nausea rather than treating vomiting, though antihistamines appear to be the best of all classes in treating it once it has begun. Their effectiveness is likely due to their central anticholinergic properties that reduce activity in the vestibular nuclei. The nonsedating antihistamines (ie, those that do not cross the blood-brain barrier) do not appear to be effective in either preventing or treating nausea and vomiting. Common adverse effects can include dry mouth/nose/throat, drowsiness, and sensitivity to bright light (secondary to mydriasis). Less common adverse effects include palpitations, urinary retention, bloating, constipation, headache, and confusion. They should be taken 1 hour prior to departure.
Cyproheptadine
Cyproheptadine is a nonselective antihistamine effective against CVS and migraines. It is also an appetite stimulant. Therapeutic effects are observed within 1-2 weeks. This agent is an excellent choice for children younger than 5 years.
Diphenhydramine (Benadryl)
Diphenhydramine is used for treatment and prophylaxis of vestibular disorders that may cause nausea and vomiting. It provides mild sedation, as well as antinausea and antiemetic actions synergistic with those of 5-HT3 antagonists.
Antidepressants, TCAs
Class Summary
Tricyclic antidepressants are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects. They may block the active reuptake of norepinephrine and serotonin.
Amitriptyline
Tricyclic antidepressants (TCAs) such as amitriptyline are excellent first-line choices in children older than 5 years. Amitriptyline has anticholinergic and sedating side effects and thus is best administered at bedtime. Cardiac arrhythmia, especially in overdose, has been described; monitoring the QTc interval both before therapy is initiated and after the target level has been reached is advised. Up to 1 month may be needed for clinical effects to become evident.
Beta-Adrenergic Blocking Agents
Class Summary
Beta-blockers may reduce the frequency and severity of episodes. Propranolol is usually recommended because of its CNS penetration.
Propranolol (Inderal LA, InnoPran XL)
Propranolol is a beta-adrenergic blocker and an excellent first-line agent for prophylaxis when used at low doses. It has a 57% efficacy rate, with efficacy defined as a 50% reduction in the frequency and severity of episodes. It requires 1 week for efficacy and requires gradual withdrawal over 1 week. Dosing may be monitored on the basis of a fall in presleep resting pulse from baseline; a decline of less than 15-20 beats/min indicates that the dose may be further increased.
Anticonvulsants
Class Summary
Agents that inhibit brain glutamate decarboxylase, which causes a decrease in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), may help reduce the frequency and severity of episodes.
Phenobarbital
Phenobarbital may be used in patients with or without electroencephalographic (EEG) changes. A 79% response rate has been observed in patients with CVS.
Topiramate (Topamax)
Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of antiepileptic activity; it may have state-dependent sodium channel blocking action. It potentiates the inhibitory activity of the neurotransmitter GABA. In addition, topiramate may block glutamate activity and, in turn, help reduce the frequency and severity of episodes.
Zonisamide (Zonegran)
Zonegran blocks T-type calcium channels, prolongs sodium channel inactivation, and is a carbonic anhydrase inhibitor.
Levetiracetam (Keppra, Keppra XR)
Levetiracetam may facilitate GABAergic inhibitory transmission through displacement of negative modulators.
Antibiotics
Class Summary
Antibiotics with prokinetic activity in the stomach may be used.
Erythromycin (E.E.S., Ery-Tab, Erythrocin)
Erythromycin is a gastric prokinetic that stimulates coordinated gastric emptying. A 75% response rate has been demonstrated in patients with CVS.
Sumatriptan (Imitrex, Sumavel DosePro)
The 5-HT1B/1D agonist sumatriptan may effectively terminate an episode of CVS by constricting the cerebral vasculature. High doses are more effective in patients with CVS.
Anxiolytics, Benzodiazepines
Class Summary
Some agents in this class may be used for the treatment of nausea.
Lorazepam (Ativan)
Because of both their sedative properties and their antinausea effects, sedatives may be helpful. Lorazepam induces sedation and anxiolysis through central inhibition of gamma-aminobutyric acid (GABA). Its effects appear to be synergistic with the antinausea and antiemetic effects of 5-HT3 antagonists. Concomitant sedation and induction of sleep provide sustained relief from intractable nausea.
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Cyclic versus chronic temporal patterns of recurrent vomiting. Number of emeses is plotted over 2-month period. Chronic pattern, represented by thin dashed line, has low grade on nearly daily basis (eg, gastroesophageal reflux). Cyclic pattern, represented by heavy solid line, involves high-intensity episodes intermittently once every several weeks (eg, cyclic vomiting syndrome).
Tables
Characteristic |
Adults (n = 104) |
Children (n = 147) |
Number of ED visits per patient with CVS (median) |
15 (range, 1-200) |
10 (range, 1-175) |
Number of ED visits before diagnosis of CVS (median) |
7 (range, 1-150) |
5 (range, 0-65) |
Diagnosis not made in ED |
89 (93%) |
119 (93%) |
Diagnosis not recognized in ED in patients with established diagnosis of CVS |
84 (88%) |
97 (80%) |
Number of different EDs visited (mean ± SD) |
4.69 ± 4.72 |
2.6 ± 2.42 |
CVS = cyclic vomiting syndrome; ED = emergency department; SD = standard deviation. |
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Feature |
Children |
Adults |
Age of onset |
4.8 years (earliest, 6 days) |
35 years (latest, 73 years) |
Delay in diagnosis |
2.6 years |
8 years |
Female-to-male ratio |
57:43 |
17:24 |
Frequency |
Every 2-4 weeks |
Every 3 months |
Duration (mean) |
1-2 days (range, 1-10 days) |
6 days (range, 1-21 days) |
Periodicity |
49% |
Not reported |
Early morning onset |
42% |
50% |
Stereotypical episodes |
99% |
85% |
Prodrome |
72%, 1.5 hours |
93% |
Symptoms |
Nausea, anorexia, pallor |
Nausea, epigastric pain |
Recovery to oral feeding |
6 hours |
24 hours |
Relieving factors |
Deep sleep |
Hot bath or shower (56%) |
Precipitating factors |
Stress (47%), infection (31%) |
Menses (57%), anxiety |
Comorbid conditions |
Anxiety |
Not reported |
Inter episodic nausea |
< 6% |
63% |
Coalescence of episodes |
Few |
50% |
Vomiting |
6 episodes/hr at peak, bile (81%) |
8.5 episodes/hr |
Systemic symptoms |
Pallor, salivation, listlessness |
Intense thirst (33%) |
GI symptoms |
Anorexia, nausea, diarrhea, abdominal pain |
Abdominal pain, diarrhea |
Neurologic symptoms |
Headache, photophobia, phonophobia, abdominal pain |
Irritability, confusion |
Natural history |
=28% progress to migraine |
Not reported |
Family history |
82% |
57% |
Complications |
Dehydration, esophagitis |
Dehydration, esophagitis, laparotomy (18%) |
Morbidity |
14-25 days of missed school per year |
32% completely disabled |
