Treating Patients with Chronic Constipation or IBS

Chicago—Between 25 million and 45 million people in the United States have irritable bowel syndrome (IBS), a disorder associated with abdominal pain and discomfort and an altered bowel habit. An additional 42 million people have chronic constipation, a condition characterized by bloating and impaired bowel movements.

During a satellite symposium at DDW, the speakers discussed IBS and chronic constipation and treatment options available for these diseases. The session was supported by educational grants from Forest Laboratories, Inc., Ironwood Pharmaceuticals, and Takeda Pharmaceuticals International, Inc.

IBS Overview

IBS affects individuals of all ages, although most are <50 years of age. There are 3 times more females than males with IBS, and the condition is more common in nonwhites than whites.

Each year, there are approximately 3.5 million physician visits related to IBS, according to William Chey, MD, director, gastrointestinal physiology laboratory, co-director, Michigan Bowel Control Program, University of Michigan Health System.

Dr. Chey added that a study found patients with IBS had 50% higher direct costs than a control group and were 3 times more likely to undergo cholecystectomy. There are also indirect costs: 3% to 5% of people with IBS are absent from work, while 26% to 31% have impaired productivity. Another study found scores on the Short Form 36 Health Survey (SF-36) for people with IBS were lower than for other chronic illnesses. The SF-36 measures health-related quality of life.

The Rome III Diagnostic Criteria for IBS includes recurrent abdominal pain or discomfort for at least 3 days per month in the last 3 months associated with ≥2 of the following: (1) improvement with defecation; (2) onset associated with a change in frequency of stool; and (3) onset associated with a change in the form of stool. Dr. Chey noted the criteria must be fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis of IBS.

The Bristol Stool Form Scale defines IBS as chronic, recurrent abdominal pain or discomfort that is not explained by structural or biochemical abnormalities. There are 7 types of IBS, and the condition is commonly referred to as IBS with constipation, IBS with diarrhea, and mixed type IBS.

When diagnosing IBS, physicians typically examine a person’s symptom severity and duration, family history, and psychosocial factors. Sometimes patients are given initial screening tests, such as a complete blood count or stool hemoccuit. If clinical evidence suggests people have organic disease, they undergo laboratory tests, colonoscopy, or sigmoidoscopy. Common laboratory tests include sedimentation rate, serum chemistry, thyroid function, stool ova, and parasites.

Chronic Constipation Overview

Dr. Chey said 2 million people with chronic constipation visit doctors each year, while an estimated 48,450 patients are hospitalized with the condition on an annual basis. Chronic constipation occurs in people of all ages, but the prevalence increases in people who are ≥65 years of age. Two times as many females as males have the disease. People with chronic constipation also have lower scores on the SF-36 compared with healthy people, according to Dr. Chey.

The Rome III Diagnostic Criteria for chronic constipation includes symptoms that are insufficient to satisfy the IBS criteria as well as ≥2 of the following: (1) <3 defecations per week; (2) straining; (3) lumpy or hard stools; (4) sensation of incomplete evacuation; or (5) facilitation by manual maneuvers during at least 25% of defecations. People with IBS rarely have loose stools present when they are not using laxatives for assistance, according to Dr. Chey.

Unlike with IBS, the Rome III Diagnostic Criteria for chronic constipation does not mention abdominal pain or discomfort. However, people with IBS with constipation and chronic constipation share symptoms such as bloating and pain. Dr. Chey noted that a study found patients with IBS with constipation had significantly greater frequency of abdominal pain and discomfort and more severe symptoms, although 44.8% of patients with chronic constipation had abdominal pain or discomfort within the past 3 months. He mentioned that some patients with chronic constipation have abdominal pain and discomfort without fulfilling the IBS criteria.

Although a large number of people have chronic constipation, Dr. Chey said there are common misconceptions associated with the condition, including with fiber intake, fluid intake, and stimulant laxatives. He noted that patients with more severe constipation may experience worsening conditions if they eat foods with fiber, while there is no evidence that drinking fluids is effective for constipation unless a person is dehydrated. In addition, he mentioned that there is no convincing evidence that chronic use of stimulant laxatives causes structural or functional impairment of enteric nerves or intestinal smooth muscle. There is also no reliable data linking the chronic use of stimulant laxatives to colorectal cancer and other tumors. People may misuse laxatives, according to Dr. Chey, although there is no potential for addiction.

Some medications may contribute to chronic constipation, according to Brian Lacy, MD, professor of medicine, division of gastroenterology and hepatology, Dartmouth-Hitchcock Medical Center; he mentioned nonprescription drugs, such as antacids, calcium supplements, iron supplements, antidiarrheal agents, and nonsteroidal anti-inflammatory drugs. He also noted prescription drugs, such as opioids, anticholinergic agents, calcium channel blockers, statins, antipsychotics, diuretics, and antihistamines.

Treatment Options

Lin Chang, MD, co-director, Oppenheimer Family Center for Neurobiology of Stress, division of digestive diseases, University of California, Los Angeles School of Medicine, provided an overview of the treatment options for IBS. She mentioned the choices for IBS vary depending on symptoms.

For instance, people with diarrhea take loperamide, alosetron, or antibiotics; people with bloating or distension take probiotics, antibiotics, linaclotide, or lubiprostone; people with constipation take psyllium, osmotic laxatives, linaclotide, or lubiprostone; and people with abdominal pain or discomfort take antispasmodics, antidepressants, alosetron, antibiotics, linaclotide, or lubiprostone. For chronic constipation, treatment options include fiber, osmotic laxatives, stool softeners, stimulant laxatives, lubricants, lubiprostone, and linaclotide.

Dr. Chang mentioned the American College of Gastroenterology IBS task force that performed systematic reviews and developed evidence-based recommendations. The group found fiber is appropriate to treat stool frequency and stool consistency; laxatives are appropriate for stool frequency; lubiprostone is appropriate for global symptoms, pain, and stool consistency; and linaclotide is appropriate for global symptoms, pain, bloating, stool frequency, and stool consistency. However, the recommendation and evidence for fiber and laxatives were both deemed weak. The recommendations for lubiprostone and linaclotide were considered strong, according to the task force.

Lubiprostone, an oral chloride channel activator, is FDA-approved to treat chronic idiopathic constipation in adults, opioid-induced constipation in adults with chronic, noncancer pain, and IBS with constipation in women who are ≥18 years of age. Dr. Chang cited data from 2 phase 3 trials that evaluated treatment with lubiprostone for 12 weeks. Of the patients who received lubiprostone twice daily, 17.9% had a response to the treatment compared with 10.1% of patients in the placebo group. The authors defined a response as at least 2 to 4 weeks of moderate relief per month or significant relief for more than 2 to 4 weeks per month. The relief must have lasted at least 2 months.

In a multicenter, parallel group, double-blind, controlled trial of patients with chronic constipation, the mean number of spontaneous bowel movements was 5.69 in patients who receive lubiprostone and 3.46 in the placebo group.

Linaclotide, a guanylate cyclase-C agonist, is FDA-approved to treat IBS with constipation and chronic idiopathic constipation. Dr. Chang discussed a trial that found 33.8% of patients who received linaclotide had a response to treatment after 12 weeks compared with 18.2% of patients in a placebo group. Another study found that 36.7% of patients who received linaclotide had a response after 12 weeks and 33.2% had a response after 26 weeks, while 15.6% of patients who received placebo had a response after 12 weeks and 14.1% had a response after 26 weeks. Dr. Chang also said studies have shown linaclotide led to significantly more spontaneous bowel movements and improvements in quality of life.

In trials, the most common adverse events associated with lubiprostone were nausea (31.1% of patients), diarrhea (13.2%), headache (13.2%), and abdominal pain (6.7%). The most common adverse events among patients who received linaclotide were diarrhea (18%), nausea (4%), and abdominal pain (4%). Dr. Chang said most of the adverse events were mild to moderate in severity. She added that patients who received linaclotide had a significantly higher incidence of diarrhea than a placebo group, while lubiprostone may rarely cause dyspnea. She recommended starting treatment with the lowest effective doses because linaclotide and lubiprostone may cause dose-dependent adverse events.

For IBS, there are also psychological treatment options, such as hypnotherapy, stress management, dynamic psychotherapy, and cognitive behavioral therapy. Some people are also prescribed antidepressants, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors.

To manage IBS with constipation, Dr. Chang suggested individualizing treatment based on patients’ symptoms. She said linaclotide and lubiprostone are effective at addressing multiple symptoms, including abdominal pain.