Medications for Gallstone Dissolution
Yes, ursodeoxycholic acid (ursodiol) can dissolve cholesterol gallstones, but it works in only about 30% of carefully selected patients and requires 6-24 months of treatment. 1
Mechanism and Efficacy
Ursodiol works by suppressing hepatic cholesterol synthesis and secretion, inhibiting intestinal cholesterol absorption, and changing bile composition from cholesterol-precipitating to cholesterol-solubilizing. 1 The drug disperses cholesterol as liquid crystals in aqueous media, effectively solubilizing cholesterol even when ursodiol comprises only 60% of the total bile acid pool. 1
The optimal dose is 8-10 mg/kg/day, which achieves complete stone dissolution in approximately 30% of unselected patients with uncalcified gallstones <20 mm in diameter treated for up to 2 years. 1
Patient Selection Criteria
You should only consider ursodiol for patients who meet ALL of the following strict criteria:
- Stone characteristics: Radiolucent (cholesterol) stones on plain film, <20 mm in maximal diameter 1
- Gallbladder function: Visualizing gallbladder on oral cholecystogram (functioning gallbladder required to concentrate ursodiol-enriched bile) 1, 2
- Stone composition: Uncalcified stones (calcified stones rarely dissolve) 1
- No contraindications: No pregnancy, acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-GI fistula 1, 2
Success Rates by Stone Size
The dissolution rate is inversely related to stone size: 1
- Stones ≤5 mm: 81% complete dissolution
- Floating/floatable stones (high cholesterol content): Up to 50% dissolution rate
- Stones >20 mm: Rarely dissolve
Treatment Monitoring and Duration
Begin with baseline ultrasound and oral cholecystogram, then perform serial ultrasonographic examinations every 6 months. 1
- Partial dissolution within 6 months: >70% chance of eventual complete dissolution with continued therapy 1
- Partial dissolution within 12 months: 40% probability of complete dissolution 1
- Gallbladder nonvisualization developing during treatment: Predicts failure; discontinue therapy 1
Bile ursodeoxycholic acid concentrations reach steady-state in approximately 3 weeks. 1
Critical Limitations and Pitfalls
Stone recurrence occurs in 30-50% of patients within 2-5 years after complete dissolution. 1 After stopping ursodiol, bile acid concentration falls exponentially to 5-10% of steady-state levels within 1 week. 1
Ursodiol will NOT dissolve: 1
- Calcified cholesterol stones
- Radiopaque stones
- Radiolucent bile pigment stones
- Stones in cystic fibrosis patients (cholesterol is not the main component) 3
Comparison with Alternative Therapies
The 1993 American College of Physicians guideline notes that ursodiol is limited to only 20% of cholecystectomy candidates and requires daily dosing for up to 2 years. 4 Surgical cholecystectomy prevents future pain, complications, stone recurrence, and gallbladder cancer—outcomes that medical dissolution therapy cannot achieve. 4
Ursodiol monotherapy (10 mg/kg/day) is equally effective as combination therapy with chenodeoxycholic acid (5 mg/kg each) but has fewer side effects. 5 Ursodiol is significantly more effective than chenodeoxycholic acid at both high and low doses, particularly in the first 6 months of treatment. 6
Practical Recommendation
For most patients with symptomatic gallstones, cholecystectomy remains the definitive treatment. 4 Reserve ursodiol for highly selected patients with small (<20 mm), radiolucent, uncalcified stones in a functioning gallbladder who are poor surgical candidates or refuse surgery, understanding that treatment requires 6-24 months and recurrence rates are high. 1, 4