For hiccups, would you use a combination of Reglan (metoclopramide) and baclofen?

Combination of Reglan (Metoclopramide) and Baclofen for Hiccups

For intractable hiccups, a combination of metoclopramide and baclofen is recommended as an effective treatment approach that targets multiple mechanisms of the hiccup reflex. 1

Mechanism of Action

• Metoclopramide acts as a prokinetic agent that increases lower esophageal sphincter tone and accelerates gastric emptying, addressing potential gastroesophageal reflux that may trigger hiccups 2
• Baclofen is a GABA analog with phenylethylamine properties that activates inhibitory neurotransmitters, blocking the hiccup stimulus at the central level 3
• The combination provides a synergistic effect by targeting both central (neurological) and peripheral (gastrointestinal) mechanisms of hiccups 4

Evidence Supporting This Combination

• Systematic reviews have identified both metoclopramide and baclofen as effective agents for persistent hiccups, with baclofen having the strongest evidence from randomized controlled trials 1, 4
• Case reports demonstrate that baclofen monotherapy can successfully treat intractable hiccups that have persisted for years 5
• When hiccups persist despite monotherapy, combination treatment has shown success in difficult cases 3
• Metoclopramide is specifically mentioned in guidelines as a prokinetic agent that can be considered for persistent hiccups 2

Dosing Recommendations

• Baclofen: Start with 5-10 mg three times daily, can be titrated up as needed 6
• Metoclopramide: 10 mg orally three to four times daily 2
• Begin with these moderate doses and adjust based on response and tolerability 4

Monitoring and Precautions

• Monitor for extrapyramidal symptoms with metoclopramide, including dystonic reactions, akathisia, and tardive dyskinesia 2
• Baclofen may cause drowsiness, dizziness, and weakness; start at lower doses in elderly patients or those with renal impairment 1
• Metoclopramide should be used with caution in patients with seizure disorders, GI bleeding, or GI obstruction 2
• Consider diphenhydramine availability for potential dystonic reactions from metoclopramide 2
• Limit metoclopramide use to short duration when possible due to risk of tardive dyskinesia with prolonged use 2

Alternative Options if Combination Fails

• Gabapentin (100-300 mg 2-3 times daily) has shown efficacy in case reports with minimal side effects and drug interactions 6
• Chlorpromazine is the only FDA-approved medication for hiccups but has more significant side effects 4
• Olanzapine in low doses may be effective when added to baclofen for refractory cases 3
• For hiccups related to gastroesophageal reflux, consider adding proton pump inhibitors to the regimen 2

Clinical Pearls

• Persistent hiccups (>48 hours) and intractable hiccups (>1 month) require pharmacological intervention as they significantly impact quality of life 1
• Always assess for and treat underlying causes of hiccups before initiating symptomatic therapy 4
• The combination approach is particularly valuable when monotherapy has failed 3
• Response to therapy may be rapid (within 24 hours) or may take several days to develop 6