What is the best treatment for refractory constipation?

From the Guidelines

For refractory constipation, linaclotide (145-290mcg daily) is recommended as a prescription medication for patients not responding to first-line treatments, due to its strong recommendation by the American Gastroenterological Association and American College of Gastroenterology clinical practice guideline 1.

Treatment Approach

A step-wise approach is recommended, starting with lifestyle modifications and progressing to medications and procedures if needed.

• Begin with increased fluid intake (2-3 liters daily) and dietary fiber (25-30g daily), as well as regular physical activity.
• First-line medications include osmotic laxatives like polyethylene glycol (17-34g daily) or lactulose (15-30ml daily), which draw water into the bowel.
• If these are ineffective, add stimulant laxatives such as bisacodyl (5-10mg daily) or senna (8.6-17.2mg daily).

Prescription Medications

For patients not responding to these measures, prescription medications may be necessary, including:

• Linaclotide (145-290mcg daily), which increases intestinal secretions and motility 1.
• Lubiprostone (24mcg twice daily), which is a chloride channel activator resulting in increased intestinal fluid and accelerated GI transit 1.
• Plecanatide (3mg daily) or prucalopride (2mg daily), which also work by increasing intestinal secretions or motility.

Additional Considerations

• Biofeedback therapy can help patients with dyssynergic defecation.
• In severe cases unresponsive to medical management, surgical options like subtotal colectomy may be considered, but only after thorough evaluation.
• The underlying cause of constipation should be identified and addressed, as refractory constipation may result from medication side effects, metabolic disorders, neurological conditions, or structural abnormalities 1.

From the FDA Drug Label

Patients on placebo who were allocated to LINZESS had an increase in CSBM and SBM frequency similar to the levels observed in patients taking LINZESS during the treatment period. The response rates for the CSBM responder endpoint were 13% for LINZESS 72 mcg and 5% for placebo. The difference between LINZESS 72 mcg and placebo was 9% (95% CI: 4.8%, 12. 5%). The efficacy of LINZESS in the treatment of FC in pediatric patients 6 to 17 years of age was assessed using change-from-baseline endpoints. The primary efficacy endpoint was the 12-week change from baseline in SBM frequency rate. The results demonstrated that patients who received LINZESS had statistically significant improvements compared with placebo as shown in Table 7

The best treatment for refractory constipation is Linaclotide (LINZESS) 72 mcg once daily, as it has been shown to increase CSBM and SBM frequency in adult and pediatric patients with functional constipation 2.

• Key benefits of Linaclotide include:
  • Statistically significant improvements in SBM frequency rate compared to placebo
  • Increase in CSBM and SBM frequency similar to the levels observed in patients taking LINZESS during the treatment period
  • Effective in both adult and pediatric patients (6 to 17 years of age) with functional constipation

From the Research

Treatment Options for Refractory Constipation

The treatment of refractory constipation depends on the underlying subtype of constipation, as identified through specific diagnostic examinations 3. The following options are available:

• Slow transit constipation: stimulant laxatives, osmotic laxatives, enterokinetics (such as prucalopride), or secretagogues (such as lubiprostone or linaclotide) may be effective 3
• Obstructed defecation: biofeedback may be beneficial, although medical treatment is often less effective 3
• Refractory constipation with no response to medical treatment: sacral neuromodulation, local injection of botulinum toxin, or anterograde continence enemas may be attempted, although outcomes are unpredictable 3
• Surgical options: subtotal colectomy with ileorectal anastomosis or stapled transanal rectal resection may be considered in selected patients with refractory constipation 3, 4, 5

Evaluation of Refractory Constipation

A comprehensive evaluation algorithm is necessary for the management of patients with refractory constipation, including:

• Physiological assessment to identify the subtype of constipation 4
• Differentiation of subtypes of primary chronic idiopathic constipation 5
• Identification of associated diseases that may be contributing to refractory constipation 5
• Individualized treatment based on the subtype and underlying disease 5

Laxative Therapy

The choice of laxative therapy may depend on the specific characteristics of the patient and the subtype of constipation. For example:

• Senna, a stimulant laxative, may be effective in children with constipation related to anorectal malformation 6
• Polyethylene glycol, an osmotic laxative, may be used in patients with idiopathic constipation, although senna may be more effective in certain cases 6