Chronic constipation: Let symptom type and severity direct treatment
How various therapies fit into the scheme of things; what is unlikely to help.
Novel therapies
Tegaserod
Tegaserod (Zelnorm) is FDA-approved for treatment of women with IBS whose primary bowel symptom is constipation, and for treatment of chronic idiopathic constipation in women and men aged <65.23 The ACG Task Force determined that tegaserod increases the frequency of complete spontaneous bowel movements (CSBM), decreases straining, and improves stool consistency in patients with chronic constipation (ACG grade: A).1 Tegaserod binds with high affinity at human 5-HT4 receptors and augments peristalsis, increases colonic motility along the entire GI tract, and promotes intestinal secretions.23,24 (For more information on tegaserod’s mode of activity, see www.jfponline.com.)
Adverse effects. The most noteworthy adverse effect of tegaserod was diarrhea, occurring as brief episodes that were generally mild (not requiring antidiarrheal drugs), transient (occurring early after initiation of treatment and resolving after a couple of days), and self-limiting.25,26 Results of a single-blind, uncontrolled extension study in which 842 patients were administered tegaserod 2 mg or 6 mg for up to 13 months (total exposure was up to 16 months) were similar to those of shorter term studies, indicating that long-term treatment is safe and well-tolerated.27
Important advice for patients. Although tegaserod is generally well tolerated, counsel patients regarding its potential risk. Ischemic colitis, a vascular disorder that results from reduced blood flow in the colon, appears as a precaution in the current package insert.23 No cases of this condition were reported during clinical trials. Although reports of transient ischemic colitis were reported during postmarketing surveillance, they were not associated with long-term consequences, and they occurred at the expected rate in the general population and lower than the rate observed in IBS patients.23,28 To date, no vascular mechanism has been found that links colonic ischemia with tegaserod use.29 Nevertheless, patients for whom tegaserod is prescribed should be counseled to promptly report any symptoms consistent with this condition, including worsening abdominal pain, rectal bleeding, or bloody diarrhea.23
Lubiprostone
Lubiprostone (Amitiza) is a chloride channel activator that increases secretion of intestinal fluid. This agent significantly increases stool frequency, improves stool form, and decreases straining,30-32 and was recently FDA-approved for the treatment of patients with chronic idiopathic constipation.33 To date, data from lubiprostone clinical trials have not been published in full. As more data become available, it will be interesting to evaluate where this agent fits into the growing treatment armamentarium for chronic constipation.
Drugs in the pipeline
Several additional pharmacologic classes with unique modes of action are under investigation for the treatment of chronic constipation, including opioid antagonists and neurotrophic factors.34
When to use which agent
In the absence of specific guidelines dictating an order of treatment options for patients with chronic constipation, base your decision on such factors as the degree to which symptoms affect a patient’s daily life, results achieved with agents in the past, patient preference, and your clinical judgment and experience ( FIGURE ). Lifestyle modifications and traditional (primarily over-the-counter) therapies are typically the initial approaches for patients with milder symptoms. Patients experiencing moderate to severe constipation-associated symptoms, those who have experienced adverse effects, and those who have not achieved satisfactory relief of constipation should be evaluated for other treatment options, including prescription laxatives, tegaserod, and lubiprostone.
Because of the heterogeneity of this disorder, successful management is patient specific. Positive outcomes may include increased stool frequency, less straining, sense of complete evacuation, resolution of abdominal bloating, and passage of soft, formed stool. Optimally, these positive symptom outcomes will translate into better overall quality of life and the ability to return to normal work and personal activities. Importantly, education and continual open dialogue with the patient are crucial to managing expectations, both for the physician and for the patient.
FIGURE
Chronic primary constipation: Let symptom type and severity direct treatment choices 
When referral is indicated
Though most patients with chronic constipation can be treated successfully in the primary care setting,35 a few may require referral to a gastroenterologist. Reasons may include the following:
- Suspicion of defecatory disorders (eg, pelvic floor dyssynergia)
- Lack of sufficient response to empiric treatment
- Worsening symptoms despite treatment
- Development of GI-associated alarm features requiring diagnostic procedures that may not be feasible to conduct in the primary care clinic setting (eg, balloon distension, anorectal manometry, defecography, colonic transit, barium enema, and colonoscopy).8
