Medication Summary
Various agents have been reported to cure hiccups. Chlorpromazine appears to be the drug of choice. Haloperidol and metoclopramide have been used successfully. Several anticonvulsant agents (eg, phenytoin, valproic acid, and carbamazepine) have effectively treated intractable hiccups in typical anticonvulsant doses. Gabapentin has been effective in patients with central nervous system (CNS) lesions and in some other groups.
Of the anesthetic agents, ketamine has been the most successful. Baclofen is particularly useful in patients for whom other agents are contraindicated. Lidocaine has cured patients after other agents were unsuccessful. Other reportedly beneficial agents include muscle relaxants, sedatives, analgesics, stimulants, and various miscellaneous agents (eg, edrophonium, dexamethasone, amantadine, and nifedipine). Benzodiazepines should be avoided.
Antiemetic Agents
Class Summary
Antiemetic agents are effective in treating hiccups.
Chlorpromazine
Chlorpromazine
Chlorpromazine is the drug of choice in this setting. It is an antidopaminergic agent that blocks postsynaptic mesolimbic dopamine receptors. Chlorpromazine has an anticholinergic effect, can depress the reticular activating system, blocks alpha-adrenergic receptors, and depresses the release of hypophyseal and hypothalamic hormones.
Metoclopramide (Reglan, Metozolv ODT)
Metoclopramide blocks dopamine receptors in the chemoreceptor trigger zone of the CNS.
Anticonvulsants/Antiarrhythmics
Class Summary
Anticonvulsants are used for severe muscle spasms.
Phenytoin (Dilantin, Phenytek)
Phenytoin inhibits the spread of motor activity by acting in the motor cortex.
Valproic acid (Depakote, Depakene, Depacon, Stavzor)
Although the mechanism by which valproic acid acts is not established, it may be related to increased brain levels of gamma-aminobutyric acid (GABA) or enhanced GABA action. This agent may also potentiate postsynaptic GABA responses, affect potassium channels, or exert a direct membrane-stabilizing effect.
Carbamazepine (Tegretol, Carbatrol, Equetro, Epitol)
Carbamazepine may block post-tetanic potentiation by reducing summation of temporal stimulation.
Anesthetics
Class Summary
Anesthetics that affect muscle contractions appear to be effective.
Ketamine (Ketalar)
Ketamine acts on the cortex and limbic system, decreasing muscle spasms.
Lidocaine (Xylocaine)
Lidocaine inhibits depolarization of type C sensory neurons by blocking sodium channels.
Muscle Relaxants
Class Summary
Muscle relaxants may reduce muscle contractions.
Orphenadrine (Norflex)
Although the exact mode of action is not well understood, orphenadrine has shown clinical effectiveness in treating hiccups.
Baclofen (Lioresal, Gablofen)
Baclofen may induce the hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at the spinal level. It is useful in patients for whom other agents are contraindicated (eg, those with renal impairment).
Analgesics
Class Summary
Sedative agents with effects in spastic muscles have shown effectiveness.
Morphine (Duramorph, Astramorph, Avinza, Kadian, MS Contin)
Morphine is the drug of choice for analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various IV doses are used; the dose is commonly titrated until the desired effect is obtained.
Antipsychotic Agents
Class Summary
These agents affect dopamine receptors but also affect serotonin receptors involved with frontal lobe functions.
Haloperidol (Haldol)
Haloperidol is useful in treatment of irregular spasmodic movements of muscles. It blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain. It also decreases hypothalamic and hypophyseal hormones.
Sedative/Hypnotics
Class Summary
Chloral hydrate from this drug category has been reported to be beneficial.
Chloral hydrate
Has central nervous system depressant effects. Mechanism unknown.
Antidepressants, Tricyclic Antidepressants
Class Summary
Tricyclic antidepressants are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects. They block the active reuptake of norepinephrine and serotonin.
Amitriptyline
Amitriptyline inhibits reuptake of serotonin and norepinephrine at the presynaptic neuronal membrane, which increases concentrations in the CNS. It may also have analgesic effects.
Stimulants
Class Summary
The mechanisms by which stimulants act in the treatment of hiccups are not well understood.
Ephedrine
Ephedrine stimulates release of epinephrine stores, producing alpha-adrenergic and beta-adrenergic effects.
Methylphenidate (Ritalin, Concerta, Metadate, Methylin, Daytrana)
Methylphenidate stimulates the cerebral cortex and subcortical structures.
