What are non-sedative medications for treating hiccups?

Non-Sedative Medications for Hiccups

For persistent or intractable hiccups requiring pharmacologic treatment, baclofen (5-10 mg three times daily) and metoclopramide (10-20 mg every 4-6 hours) are the preferred non-sedative first-line agents, with baclofen particularly effective for central causes and metoclopramide for peripheral causes. 1, 2

Primary Non-Sedative Options

Baclofen

• Start with 5-10 mg three times daily as the most effective non-sedative option, particularly for centrally-mediated hiccups 1, 2
• Studied in randomized controlled trials with demonstrated efficacy 3
• Acts on the hiccup reflex arc through GABA-B receptor agonism 4
• Can be titrated upward based on response and tolerability 2

Metoclopramide

• Administer 10-20 mg orally or IV every 4-6 hours for peripheral causes of hiccups 1, 5
• Particularly effective when gastroesophageal reflux or gastric distension is the underlying cause 6, 4
• One of only two agents studied in randomized controlled trials 3
• Monitor for extrapyramidal symptoms, especially in elderly patients and those with liver disease 1
• Can treat with benztropine 50 mg IM if acute dystonic reactions occur 5

Haloperidol

• Use low doses of 0.5-2 mg as an alternative antipsychotic with antiemetic and anti-hiccup properties 1
• Non-sedating at these low doses compared to chlorpromazine 3
• Monitor for extrapyramidal symptoms and QT prolongation 1

Alternative Non-Sedative Agents

Gabapentin

• Studied prospectively with demonstrated efficacy 3
• Useful when neuropathic mechanisms are suspected 4
• Dosing typically starts low and is titrated to effect 3

Other Options

• Lansoprazole may be beneficial when gastritis or reflux esophagitis is present 7
• Nifedipine and nimodipine have case report evidence but limited data 3
• Valproic acid has been reported successful in case series 3

Agents to Avoid or Use Cautiously

Chlorpromazine

• FDA-approved for hiccups at 25-50 mg three to four times daily 8
• However, this is highly sedating and causes significant hypotension, particularly in elderly patients 1, 8
• Risk of QT prolongation and extrapyramidal symptoms 1
• Not truly a "non-sedative" option despite FDA approval 6

Benzodiazepines

• Lorazepam (0.5-2 mg every 4-6 hours) may help when anxiety contributes 1
• These are sedating agents and should not be considered non-sedative options 9

Clinical Algorithm

Step 1: Identify if hiccups are central (CNS lesions, stroke) vs peripheral (gastric distension, phrenic nerve irritation) 4, 2

Step 2: For central causes, initiate baclofen 5-10 mg three times daily 1, 2

Step 3: For peripheral causes (especially GI-related), initiate metoclopramide 10-20 mg every 4-6 hours 1, 2

Step 4: If monotherapy fails, consider haloperidol 0.5-2 mg as add-on therapy 1

Step 5: For refractory cases, consider gabapentin or combination therapy with lansoprazole if reflux is present 3, 7

Critical Pitfalls

• Avoid prochlorperazine in liver disease due to increased extrapyramidal symptom risk 1
• Do not overlook drug-induced hiccups (steroids, chemotherapy, anti-Parkinson drugs) that may require discontinuation of the offending agent 4
• Monitor for sedation even with "non-sedative" agents in elderly patients 1
• Check for QT prolongation when using haloperidol or other antipsychotics 1
• Have benztropine available to treat extrapyramidal reactions from metoclopramide or haloperidol 1, 5