ABSTRACT: Better understanding of underlying brain-gut interactions provides a more rational approach to diagnosis and treatment of patients with irritable bowel syndrome.
CME OBJECTIVE: The reader will be aware of recent American College of Gastroenterology criteria for diagnosis of irritable bowel syndrome that encourage earlier, more focused therapy.
Mel Wilcox, MD, consultant and honoria: TAPP Pharmaceuticals.
As many as 58 million Americans live with the often embarrassing symptoms of irritable bowel syndrome (IBS) — chronic or recurrent abdominal discomfort or pain, diarrhea, constipation or alternating bouts of constipation and diarrhea. IBS can be disabling for patients and frustrating for physicians, who traditionally have established the diagnosis by excluding other problems with endoscopy, colonoscopy, or other costly, invasive procedures. Recent recommendations by the American College of Gastroenterology (ACG) suggest IBS should no longer be considered a diagnosis of exclusion. "IBS is an abnormality of intestinal muscle contractions, leading to abdominal discomfort associated with altered bowel patterns," says Director of UAB's Division of Gastroenterology and Hepatology Mel Wilcox, MD. "People with IBS have both altered motility and abnormal visceral sensation, leading to pain and bloating at much lower pressures than those without the disorder," he explains. "Although the exact cause of IBS remains undefined, newer studies indicate serotonin (a key mediator of gut motility), stress, genetics, and environmental factors may play a role. Scientific data increasingly support the theory that a dysregulation in brain-gut interactions, resulting in alterations in gastrointestinal motility, is the principal pathophysiologic mechanism."
Reducing Time to Treatment
A survey by the International Foundation for Functional Gastrointestinal Disorders found the average IBS patient is symptomatic for 3 years and sees three clinicians before diagnosis. The new ACG recommendations, coupled with public awareness campaigns, may help reduce the stigma of IBS symptoms and encourage patients and their physicians to seek effective treatments earlier.
Under current ACG guidelines, patients with a history consistent with IBS and no signs or symptoms of an underlying organic disease (such as unexplained weight loss, pyrexia, rectal bleeding, malnutrition, anemia, low albumin level, or elevated white blood count) may be assumed to have IBS and should progress to therapy. Nevertheless, Wilcox cautions, a more treatable diagnosis or life-threatening condition must be excluded. "Diagnostic test selection depends on risk factors specific to each patient. For example, lower abdominal cramps worsening over the last year in an 80-year-old woman might indicate a colon problem and require a barium enema or colonoscopy. In an adolescent with 6 months of cramps and diarrhea, evaluation of the small intestine and colon radiology studies should be performed," he says. "Clinicians can perform most workups for IBS. But, if a patient fails to respond to treatment, consider referral to a gastroenterologist who specializes in IBS."
Wilcox recommends patients keep a food diary to identify potential IBS symptom culprits, such as dairy or wheat products. "Caffeine, large quantities of alcohol, and foods that cause excessive gas should be avoided."
Stress and SSRIs
Numerous studies indicate patients with IBS experience more lifetime and daily stressful events, including anxiety and emotional, sexual, or physical abuse, compared with healthy individuals, and school and work absenteeism is three times higher in IBS patients.
"Some diseases seem to be more easily triggered by stress, which appears to play a significant role in the presentation of IBS. Even though stress universally affects gut function, IBS patients seem to react more severely to stress, compared with those who do not have the condition," Wilcox says.
Some evidence suggests tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) help control the dual physiological and psychological symptoms affecting the majority of those with the disorder. Antidepressants may be effective in smaller doses than those typically used to treat depression and also may modulate intestinal function and regulate psychological factors. The combination of psychotherapy and medical therapy also has produced encouraging results.
Diagnostic Criteria for IBSIn the absence of structural or metabolic abnormalities, continuous or recurrent symptoms of abdominal pain or discomfort that is:
- relieved with defecation; or
- associated with a change in consistency or frequency of stool.
Two or more of the following for at least a quarter of occasions or days: - altered stool frequency (>3 bowel movements/d or <3 bowel movements/wk);
- altered stool form (lumpy/hard or loose/watery stool);
- passage of mucus; or
- bloating or feeling of abdominal distension.
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Newer Treatments
A major challenge in treating IBS is the wide variety of presenting symptoms. Fiber supplements are often recommended to treat constipation-predominant IBS; for those who fail to respond, osmotic laxatives may be effective. For patients with diarrhea-predominant IBS, dietary measures and loperamide taken before meals may be beneficial. For IBS patients with severe abdominal discomfort, mild anticholinergic antispasmodic drugs, such as dicyclomine or hyoscyamine, help inhibit the gastrocolic reflex and reduce postprandial cramps. Herbal or alternative remedies, such as lactobacillus, have not been shown to alter colonic fermentation or to improve symptoms. "Treating IBS can be difficult and often requires juggling various medications to find an effective combination," he says.
The drug tegaserod maleate (Zelnorm), approved by the Food and Drug Administration (FDA) in 2002, provides short-term, multisymptom relief in roughly 60% of women with constipation-predominant IBS, and researchers are studying its effectiveness on chronic constipation and other dysmotility syndromes. Tegaserod stimulates the digestive tract, decreasing risk of developing constipation. Taken twice daily for 4 to 6 weeks, it can be continued for an additional 4 to 6 weeks in patients who respond. It is contraindicated in patients with a history of bowel obstruction, symptomatic gallbladder disease, abdominal adhesions, or suspected sphincter of Oddi dysfunction. Current labeling restricts the drug to short-term treatment for a maximum of 12 weeks.
"I recommend patients try simple things first, such as over-the-counter osmotic laxatives, before considering Zelnorm," Wilcox says.
Long-term tegaserod recently was studied in a multinational open-label trial in which 579 patients with constipation-predominant IBS received the drug for 1 year. Only one patient discontinued the drug due to acute abdominal pain (Aliment Pharmacol Ther. 2002;16[10]:1701-1708). However, further studies are needed to evaluate risks and benefits of extending tegaserod therapy, Wilcox advises, noting that in April 2004, the drug's labeling was revised to include warnings that serious consequences of diarrhea, including hypovolemia, hypotension, and syncope, had been reported in patients taking the drug. Intestinal ischemia has also been reported in patients receiving the medication, though a causal link has not been identified.
Lotronex
For selected patients with diarrhea-predominant IBS, potential relief was within sight when, in February 2000, alosetron (Lotronex) was approved by the FDA. However, the drug was pulled 4 months later after the agency received seven reports of serious complications of constipation, resulting in the hospitalization of six women; three required surgery. The FDA simultaneously received reports of ischemic colitis in alosetron patients who recovered when the medication was stopped, although three related deaths were reported.
Demand for the drug, with recommendations for stricter labeling, led to the reapproval of alosetron in 2002 — the first drug to include a medication guide, which pharmacists are required to distribute with products posing a serious risk. Alosetron is approved only for short-term treatment of women with severe, chronic, diarrhea-predominant IBS who fail to respond to conventional therapy. Patients are instructed to contact their doctors if they suffer severe constipation, increased abdominal discomfort, or symptoms of ischemic colitis.
Alosetron is not for everyone. Fewer than 5% of patients with IBS have the severe form of the disease, and only a fraction of those with severe IBS have the diarrhea-predominant type.
"Treating IBS requires a commitment from both patient and physician to find an optimal, individualized approach. There is no cure for IBS, but people need not suffer with the pain or embarrassment of living with this disorder when effective therapies to relieve the wide variety of symptoms can dramatically improve quality of life," Wilcox concludes.
For more information:
Dr. Mel Wilcox
1.800.UAB.MIST
mist@uabmc.edu