From the Guidelines
Chlorpromazine is the most effective drug for treating intractable hiccups, as evidenced by its use in various clinical settings 1.
Treatment Options
When considering treatment for hiccups, it's essential to evaluate the severity and duration of the condition. For persistent hiccups, chlorpromazine is often the preferred choice due to its efficacy in targeting the central hiccup reflex arc. The typical dosage is 25-50 mg orally or intramuscularly, administered three to four times daily until the hiccups resolve 1.
Alternative Options
For less severe cases or when chlorpromazine is not suitable, alternative medications can be considered:
- Baclofen (5-10 mg three times daily) may be tried first due to its better side effect profile.
- Metoclopramide (10 mg three times daily) is another effective option.
- Gabapentin (300-900 mg daily in divided doses) or haloperidol (1-4 mg daily) can also be used.
Mechanism of Action
These medications work through different mechanisms:
- Chlorpromazine acts as a dopamine antagonist, affecting the central hiccup reflex arc.
- Baclofen is a GABA-B agonist that reduces neuronal excitability.
- Metoclopramide affects dopamine receptors and increases lower esophageal sphincter tone.
Initial Approach
Before starting pharmacological treatment, simple physical maneuvers should be attempted, such as:
- Breath holding
- Drinking cold water
- Stimulating the posterior pharynx It's also crucial to identify and address any underlying causes of hiccups, as medications treat symptoms rather than the root cause.
From the FDA Drug Label
Intractable Hiccups– 25 mg to 50 mg t.i.d. or q.i.d. If symptoms persist for 2 to 3 days, parenteral therapy is indicated. INTRACTABLE HICCUPS If symptoms persist for 2-3 days after trial with oral therapy, give 25 to 50 mg (1-2 mL) IM. Should symptoms persist, use slow IV infusion with patient flat in bed: 25 to 50 mg (1-2 mL) in 500 to 1000 mL of saline.
Chlorpromazine is the drug of choice for intractable hiccups. The recommended dosage is 25 mg to 50 mg orally t.i.d. or q.i.d. If symptoms persist, parenteral therapy with 25 to 50 mg IM or slow IV infusion may be indicated 2 3.
From the Research
Drug of Choice for Hiccup
- The US Food and Drug Administration has approved chlorpromazine for the treatment of hiccups 4.
- Other pharmacologic treatments that have been proposed for intractable and persistent hiccups include amitriptyline, baclofen, gabapentin, haloperidol, metoclopramide, midazolam, nifedipine, nimodipine, orphenadrine, and valproic acid 4.
- Metoclopramide is also widely employed for the treatment of intractable hiccups 5.
- Baclofen, gabapentin, and metoclopramide have been studied in a prospective manner, and only baclofen and metoclopramide have been studied in randomized controlled trials 4.
- Other treatment options for intractable hiccups include vagus nerve stimulation 6, olanzapine and baclofen combination therapy 7, and risperidone 8.
Treatment Selection
- Therapy selection should be specific to individual patients, their underlying comorbidities, etiology of hiccups, and take into account the individual properties of the drugs 4.
- No specific recommendations can be made for treating intractable and persistent hiccups with the evidence currently available in the literature 4.
Pharmacologic Agents
- Chlorpromazine and metoclopramide are two of the most widely employed agents for the treatment of intractable hiccups 5.
- Baclofen is a c-aminobutyric acid (GABA) analog that contains a phenylethylamine moiety, and it is hypothesized that having both GABA and phenylethylamine properties activates inhibitory neurotransmitters, which may in turn block the hiccup stimulus 7.
- Olanzapine is thought to be effective in patients with hiccups due to its serotonin augmenting phrenic motoneuronal activity on the reflex arcs involved in the generation of hiccups within the spinal cord, and its dopamine antagonist properties 7.
- Risperidone, a dopamine-serotonin antagonist, has been shown to be effective in abolishing intractable hiccups in some cases 8.