What are the treatment options for medication-resistant constipation?

From the Guidelines

For medication-resistant constipation, I recommend starting with lifestyle modifications and escalating pharmacological interventions, prioritizing the use of polyethylene glycol (PEG) as the first-line treatment, as suggested by the most recent guideline from the American Gastroenterological Association and the American College of Gastroenterology 1. The management of medication-resistant constipation requires a multi-faceted approach, considering the patient's overall health, potential underlying causes, and the impact of constipation on their quality of life.

• Key lifestyle modifications include:
  • Increased fluid intake (2-3 liters daily)
  • Dietary fiber (25-30g daily)
  • Regular physical activity
• Pharmacological interventions should be escalated as needed, starting with:
  • Osmotic laxatives like polyethylene glycol (Miralax) 17g daily, which draws water into the bowel to soften stool, as recommended by 1
  • If ineffective, consider adding stimulant laxatives such as bisacodyl 5-10mg or senna 8.6-17.2mg daily
  • For persistent constipation, consider adding secretagogues like lubiprostone 24mcg twice daily or linaclotide 145-290mcg daily, which increase intestinal fluid secretion and motility, as mentioned in 1 and 1
  • Prucalopride 2mg daily is another option that enhances colonic motility
  • Enemas or suppositories like bisacodyl or glycerin can provide immediate relief for severe cases It is essential to address the specific underlying cause of medication-resistant constipation, which may include gut motility disorders, neurological issues, or medication side effects, as highlighted in 1 and 1.
• If these measures fail, testing for underlying conditions like pelvic floor dysfunction, which might require biofeedback therapy, should be considered. The goal of treatment is to alleviate symptoms, improve quality of life, and minimize the risk of complications, as emphasized in 1.

From the FDA Drug Label

The efficacy of prucalopride tablets for the treatment of CIC was evaluated in six double-blind, placebo-controlled, randomized, multicenter clinical trials in 2484 adult patients Eligible patients required a history of chronic constipation defined as having fewer than 3 spontaneous bowel movements (SBMs) per week that resulted in a feeling of complete evacuation Prucalopride tablets 1 or 2 mg once daily increased the number of high amplitude propagating contractions (HAPCs) during the first 12 hours as compared with an osmotic laxative treatment In the Intent-to-Treat [ITT] population in the 6 trials, 1237 received prucalopride tablets 1 or 2 mg and 1247 received placebo.

Medication Resistant Constipation Treatment with Prucalopride

• Prucalopride is effective in treating chronic idiopathic constipation (CIC), with a significant increase in the number of complete spontaneous bowel movements (CSBMs) per week.
• The medication has been shown to be effective in improving bowel motility and increasing the frequency of CSBMs.
• Prucalopride is a serotonin type 4 (5-HT4) receptor agonist, which stimulates colonic peristalsis and increases bowel motility.
• The recommended dose of prucalopride is 1-2 mg once daily, with the majority of patients responding to the 2 mg dose.
• Prucalopride has been evaluated in six double-blind, placebo-controlled clinical trials, demonstrating its efficacy and safety in treating CIC 2, 2, 2.

From the Research

Medication Resistant Constipation

• Constipation is a common gastrointestinal motility disorder that can be chronic and negatively affect patients' daily lives 3.
• Various treatment modalities are available, including nonpharmacologic and pharmacologic agents, but the clinical evidence supporting their use varies widely 3, 4.
• Traditional pharmacologic agents, such as laxatives and fiber supplements, may have limited efficacy in patients with chronic constipation, although some studies suggest benefit with psyllium, polyethylene glycol, and lactulose 3.
• Newer agents, such as tegaserod and lubiprostone, have been approved for the treatment of chronic constipation based on comprehensive clinical investigation programs 3.
• More recent studies have evaluated the efficacy and safety of over-the-counter (OTC) treatments for chronic constipation, including polyethylene glycol-based preparations, senna, and other agents 5, 6.
• The evidence suggests that polyethylene glycol and senna are effective as first-line laxatives, with good evidence supporting their use 5, 6.
• Other agents, such as fiber supplements, fruits, stimulant laxatives, and magnesium-based products, have moderate evidence supporting their use 5, 6.
• Senna has been shown to be effective in children with constipation related to anorectal malformation, with a randomized controlled trial demonstrating its superiority over polyethylene glycol 7.

Treatment Options

• Nonpharmacologic modalities, such as increased exercise or fluid intake and bowel habit training, are generally recommended as first-line approaches 3.
• Pharmacologic agents, including laxatives and fiber supplements, may be used in patients who do not respond to nonpharmacologic modalities 3, 4.
• Newer agents, such as prucalopride, have been evaluated in clinical trials and may be effective in patients with chronic constipation 4.
• OTC treatments, including polyethylene glycol-based preparations and senna, are available and may be effective in patients with chronic constipation 5, 6.

Efficacy and Safety

• The efficacy and safety of various treatment modalities for chronic constipation have been evaluated in clinical trials 3, 4, 5, 6, 7.
• Polyethylene glycol and senna have been shown to be effective and safe in patients with chronic constipation, with good evidence supporting their use 5, 6.
• Other agents, such as fiber supplements and stimulant laxatives, may have moderate evidence supporting their use, but may also be associated with adverse effects such as abdominal pain and diarrhea 5, 6.