IBS

Irritable Bowel Syndrome

 

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During her visit to your office, Mary T. describes a number of symptoms which have been bothering her, including abdominal pain and discomfort, bloating, the need to rush to the toilet, straining to defecate, a feeling of incomplete bowel emptying, and alternating periods of diarrhea and constipation. She recounts that her abdominal pain starts or worsens after meals and is temporarily relieved by defecation. These symptoms suggest to you that Mary is suffering from irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common disorder that affects the colon, causing cramping, abdominal pain, bloating, gas, diarrhea or constipation. Despite these uncomfortable symptoms, IBS doesn’t cause permanent damage to the colon – it doesn’t cause changes in bowel tissue or increase the risk of colorectal cancer. This distinguishes it from more serious structural intestinal diseases such as ulcerative colitis and Crohn’s disease.

IBS often begins during the teen years or early adulthood, but it can occur at any age. It is the most common intestinal problem that requires referral to a gastroenterologist.  About 1 in 6 people in the U.S. have symptoms of IBS, and it occurs twice as often in women as in men.[1]

Causes

The exact cause of IBS is unknown. Sometimes it occurs following an infection of the intestines, a condition known as post-infectious IBS. Another possible cause takes into account the fact that there is a connection between the intestines and the brain. As neurological impulses travel back and forth between the bowel and brain, they affect bowel function and can give rise to symptoms. During times of stress, the nerves in this pathway can become more active and sensitive, increasing the awareness and intensifying the contraction of the intestines.[2]

A number of other factors may contribute to the development of IBS. For example, people with IBS may have abnormally high serotonin levels in the gut[3] Serotonin is a chemical messenger and neurotransmitter that, among things, plays a vital role in normal digestive system function. 95% of the body’s serotonin is found in the gut. It is probable that an imbalance between serotonin and the serotonin transport (SERT) involved in the digestive process is a factor in IBS.[1]

In IBS, the contractions of the intestinal muscles that move food through the digestive system may be stronger and last longer than normal. Food is thus forced through the intestines more rapidly, causing gas, bloating, and diarrhea. In other cases, the opposite occurs; food passage slows, causing stools to become hard and dry. In a study by Cann et al., the time taken for a solid meal to pass through the stomach, small intestine, and colon was measured in 61 patients with IBS and 53 healthy volunteers. In the patients with IBS, small bowel transit times were significantly shorter in those who complained primarily of diarrhea and significantly longer in those who complained primarily of constipation or pain and distension. Whole gut transit times were shorter in patients who complained of diarrhea and longer in patients with constipation.[4]

For reasons that remain unclear, people with IBS may have a pain reaction to stimuli that don’t bother other people. Additionally, in IBS patients experiencing diarrhea and abdominal pain, there are significantly more high-amplitude propagating contractions, which are of higher amplitude than those observed in healthy controls, and these high-amplitude propagating contractions are more likely to be associated with a sensation of pain.[5]

Triggers for IBS can include certain foods, medications, or emotions. Many people find that their symptoms become worse when they eat certain foods. Chocolate, milk, and alcohol might cause constipation or diarrhea. Carbonated beverages and some fruits and vegetables may lead to bloating and discomfort in some people.

Stress, conflict, or emotional turmoil exacerbates IBS symptoms. In addition, because women are more likely to have IBS, researchers believe that hormonal changes may be a contributing factor to this condition. Many women find that their symptoms are worse during or around their menstrual periods.[6]

Symptoms

Abdominal pain and bloating are the hallmark symptoms of IBS, but symptoms can vary from person to person. Some people have constipation, straining, and cramping when trying to have a bowel movement but cannot eliminate any stool. Others experience diarrhea, which is the passage of three or more frequent, loose, watery stools per day. People with diarrhea frequently feel an urgent and uncontrollable need to have a bowel movement. Some people with IBS alternate between constipation and diarrhea; their symptoms subside for a few months and then return, while others report a constant worsening of symptoms over time.

Diagnosis

A diagnosis of IBS is based on identifying positive symptoms consistent with the condition and excluding other conditions with similar clinical presentations, which may include organic or other functional disorders.

There is no specific test that enables you to diagnose IBS. Because there are usually no physical signs to definitively diagnose IBS, diagnosis is often a process of elimination. A complete medical history and physical exam are essential in an effort to establish a diagnosis. In the diagnostic process, differential diagnoses must be done to eliminate conditions with similar symptoms.

Lactose intolerance, for example, can mimic IBS with symptoms including abdominal pain, gas, and diarrhea. Celiac disease which is caused by a reaction to gliadin, a prolamin (gluten protein), a sensitivity to wheat protein, may also cause signs and symptoms similar to those of irritable bowel syndrome. Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, can also have some of the symptoms associated with IBS. Other common illnesses that may be confused with IBS include drug-induced diarrhea, post-cholecystectomy diarrhea, laxative abuse, parasitic diseases (eg, giardiasis), eosinophilic gastritis or enteritis, microscopic colitis, and early inflammatory bowel disease.[7]

The nature of bowel patterns, the timing and distinctive features of pain, and the exclusion of other diseases through physical examination and routine diagnostic tests are all part of the diagnostic process. Ischemic colitis should be considered in patients older than 60 years who present with pain after eating. If malabsorption is suspected, tropical sprue, celiac disease, and Whipple’s disease should be considered. The work-up might include stool sample analysis, blood tests, x-rays, and sigmoidoscopy or colonoscopy depending on the differential diagnosis.[8]

To aid in the diagnostic process, researchers have developed criteria known as Rome criteria. According to these criteria, a person must have certain signs and symptoms before a doctor can diagnose IBS. The most current are the Rome III Diagnostic Criteria for IBS:

Diagnostic Criteria*[9]

Recurrent abdominal pain or discomfort** at least 3 days a month in the last 3 months associated with two or more of the following:

  1. Improvement with defecation
  2. Onset associated with a change in frequency of stool
  3. Onset associated with a change in form (appearance) of stool

*Criterion fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis

** “Discomfort” means an uncomfortable sensation not described as pain. In pathophysiology research and clinical trials, a pain/discomfort frequency of at least 2 days a week during screening evaluation is recommended for subject eligibility.

Treatment Approaches

The exact cause of IBS is uncertain; therefore treatment focuses on the relief of symptoms. In most cases, your patients can successfully control mild signs and symptoms by learning to manage stress, identifying and avoiding the foods that cause problems, and making changes in their lifestyle. If your patient’s problems are moderate to severe, you may suggest the following, which are specific clinical practice recommendations for improving IBS symptoms (Table 1):


After the above recommendations are reviewed, the following can be considered:

  • Over-the-counter medications, such as loperamide (Imodium), can help control diarrhea. Loperamide is the only antidiarrheal agent sufficiently investigated for use in IBS that results in a reduction in stool frequency and improvement in stool consistency. Loperamide has not been shown to reduce pain, bloating, or global symptoms of IBS.
  • Some patients may need anticholinergic medications to relieve painful bowel spasms. These may be helpful for people who have bouts of diarrhea, but can make constipation worse.[11]
  • Over the counter enteric-coated peppermint oil (0.2 ml TID PRN) has been shown in small studies to help those with gas pains and bloating. Side effects include increased heartburn and it should be avoided in those sensitive to menthol.[12]

Medication for Treating IBS

Three medications are currently approved for treating the symptoms of IBS.

Alosetron (Lotronex) is a serotonin specifically a 5-HT3 receptor antagonist which relaxes the colon and slows the movement of waste through the colon. Alosetron 1 mg twice daily provides relief of IBS pain and discomfort, and improves stool consistency in men and women with diarrhea-predominant IBS.[13,14] It was withdrawn from the U.S. market in 2000 due to its association with ischemic bowel and complications of severe constipation including surgery and even death. It was re-instated in 2002 under a restricted use policy and should only be used if other therapies have failed and should only be prescribed by those who have completed the prescribed mandated training because of the potential side effects. The most common side effect is constipation, although ischemic colitis, obstruction, ileus, impaction, toxic megacolon, and secondary bowel ischemia have been reported.[15,16]

Lubiprostone (Amitiza). Lubiprostone is approved for adult men and women who have IBS with severe constipation. It is a chloride channel activator that is taken twice a day, and increases fluid secretion in the small intestine to help with the passage of stool. Common side effects include nausea, diarrhea, and abdominal pain. The drug is generally prescribed only for those for whom other treatments have failed[17,18]

Tegaserod (Zelnorm) (4 or 12 mg/day for 12 weeks), is mostly of historical importance as an another drug that acting on the gut serotonin receptor, this time as a 5-HT4 agonist that stimulates smooth muscle in the gastrointestinal tract, produces some benefit over placebo when used to treat IBS where constipation is a major symptom. Patients taking tegaserod experience an overall improvement in their IBS symptoms, an increase in number of bowel movements per day, and a reduction in number of days without bowel movements. It was withdrawn from the market in 2007 due to a possible increase risk of cardiovascular events. The FDA will only authorize tegaserod in emergency situations. Requests for tegaserod for this purpose may be made to the FDA which in turn authorizes shipment of the drug by the manufacturer.[19]

Linaclotide (Linzess) is a novel intestinal secretagogue approved by the FDA in August, 2012 to treat chronic idiopathic constipation and to treat irritable bowel syndrome with constipation (IBS-C) in adults. Linzess is a capsule taken once daily on an empty stomach, at least 30 minutes before the first meal of the day. Linzess helps relieve constipation by helping bowel movements occur more often. In IBS-C, it may also help ease abdominal pain.

Linzess is approved with a Boxed Warning to alert patients and health care professionals that the drug should not be used in patients 17 years of age and younger. The most common side effect reported during the clinical studies was diarrhea.[28]

Antidepressants

Several antidepressants are prescribed for the treatment of IBS. These include tricyclic’s (TCAs) such as amitriptyline, desipramine, imipramine, and doxepin, as well as SSRIs such as fluoxetine, sertraline, paroxetine, and citalopram, or less frequently, novel antidepressants such as venlafaxine and mirtazapine. The rationale for use of these medications to treat IBS includes (1) reduction of central pain perception arising from afferent signals in the gut,[20] (2) modification of GI physiology such as visceral sensitivity, motility, and secretion,[21] and (3) treatment of psychiatric comorbidities such as major depression and/or anxiety disorders usually associated with IBS.[22]

TCAs generally have proven to be more effective than SSRIs. Antidepressants are used on a continual, rather than an “as needed” basis, therefore they are usually prescribed for patients who have chronic or frequently recurring symptoms. Low doses of TCAs (10–50 mg/day) are effective for treating pain and sleep difficulties associated with IBS, probably because of their multiple receptor blocking effects (anticholinergic, antihistaminergic), in addition to their nonselective monoamine uptake inhibition (serotonin, noradrenaline). Lower doses of TCAs also result in a more rapid onset of action than full doses used for treating major depression and they don’t pose the risk of the potentially serious cardiovascular side effects associated with full antidepressant doses.[23] Significant side effects of high-dose TCAs include increased risk of suicidality in children, adolescents, and young adults, sedation, hypotension, ventricular arrhythmias, and constipation, thus there is a greater need for dosage adjustments and a greater risk for overdose. If used in higher doses, physicians should be aware of these risks and monitor their patient carefully.

SSRIs are often prescribed for older patients because of their lower side effect profile. They also are superior in treating associated emotional symptoms of anxiety, panic, obsessional behaviors, and constipation-predominant IBS. Specific agents may be considered for particular circumstances. Fluoxetine has a long half-life and may be selected when poor compliance is an issue; citalopram has a low side effect profile and may prove beneficial because of peripheral effects on colonic tone and sensitivity in IBS[24]; and paroxetine, because of its greater anticholinergic effect, may be selected for patients with diarrhea.

The pharmacological agents that were approved for the treatment of IBS and then withdrawn have left a therapeutic vacuum for patients suffering from IBS. There is an opportunity to review and critically evaluate current knowledge of lactic acid bacteria (LAB) used to treat symptoms of IBS. A multistrain probiotic preparation in a double blind placebo controlled study of 60 patients who met Rome III criteria showed a greater improvement in the symptom severity score of IBS, severity and frequency of pain or discomfort, abdominal distention and satisfaction with bowel habits.[25] A review of 42 trials of lactic acid bacteria for IBS indicates that it can be a promising candidate for IBS therapy.[26] Probiotics should be considered, selecting one product at a time and monitoring their effects. There is no harm associated with probiotics for individuals with IBS. More studies are warranted.[9]

Lifestyle Changes

In many cases, simple dietary and lifestyle changes can provide relief from IBS. Advise your patients that although their body may not respond immediately to these changes, the goal is to find long-term solutions.

Incorporate dietary fiber. Although dietary fiber helps reduce constipation, it can also make gas and cramping worse. The best approach is to very gradually increase it over a period of weeks. Foods that contain fiber include whole grains, fruits, vegetables and beans, fiber supplements, such as psyllium (Metamucil) or methylcellulose (Citrucel), may help relieve constipation. Advise your patient that if they take a fiber supplement such as Metamucil or Citrucel, they should be sure to introduce it gradually and drink plenty of water every day to minimize gas, bloating, and constipation. Wheat bran should be avoided.

Avoid problem foods. Caution your patient to avoid foods that make their symptoms worse. Food that often aggravate IBS include alcohol, chocolate, caffeinated beverages such as coffee and sodas, dairy products, and sugar-free sweeteners (sugar alcohols may have a laxative effect as even low doses). Foods that cause excessive gas include beans, cabbage, cauliflower, and broccoli. Fatty foods can also cause problems in some people.

Use caution with dairy products. If your patient is lactose intolerant, suggest substituting yogurt for milk or using lactose-free milk. In some cases patients may need to eliminate dairy foods completely, but in these cases they need to get enough protein and calcium from other sources.

Drink plenty of liquids. Emphasize the importance of drinking plenty of fluids every day. Water is best. Alcohol and caffeinated beverages stimulate the intestines and can make diarrhea worse, and carbonated drinks can produce gas.

Exercise regularly. Exercise stimulates normal contractions of the intestines. If the patient has been inactive, advise them to start slowly and gradually increase the amount of exercise time. A recent study showed substantial increased physical activity improves GI symptoms in IBS. The study concluded that physical activity should be used as a primary treatment modality in IBS.[27]

Stress Management and Biofeedback. For patients where there is a link between their stress and the symptoms, techniques to reduce stress including biofeedback may help.

 

Gerald W. Keister
Published on August 28, 2012
Updated on August 31, 2012

 

References

    1. MPR, Monthly Prescribing Reference. Irritable Bowel Syndrome (IBS) Treatments. Accessed at: http://www.empr.com/irritable-bowel-syndrome-ibs-treatments/article/166496
    2. Merat S, Khalili S, Mostajabi P, et al. The effect of enteric-coated, delayed-release peppermint oil on irritable bowel syndrome. Dig Dis Sci. 2010 May;55(5):1385-1390.
    3. Chang L, Ameen VZ, Dukes GE, et al. A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS. Am J Gastroenterol. 2005 Jan;100(1):115-123.
    4. Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: a meta-analysis of eight randomized, placebo-controlled, 12-week trials. Clin Ther. 2008 May;30(5):884-901.
    5. Camilleri, M, Chey WY, Mayer, EA et al. A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome. Arch Intern Med. 2001;161(14):1733-1740.
    6. Boxed Warning and Medication Guide, for LOTRONEX®.  https://www.lotronex.com/
    7. Videlock EJ, Chang L. Irritable bowel syndrome: current approach to symptoms, evaluation, and treatment. Gastroenterol Clin North Am. 2007 Sep;36(3):665-685.
    8. Camilleri M, Tack JF. Current medical treatments of dyspepsia and irritable bowel syndrome. Gastroenterol Clin North Am. 2010 Sep;39(3):481-493.
    9. FDA. Zelnorm ((tegaserod maleate)/ Postmarket drug safety information for patients and providers http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm103223.htm
    10. Olden KW. The use of antidepressants in functional gastrointestinal disorders – new uses for old drugs. CNS Spectr. 2005;10(11):891-897.
    11. Gorard DA, Libby GW, Farthing MJG. Effect of a tricyclic antidepressant on small intestinal motility in health and diarrhea-predominant irritable bowel syndrome. Dig Dis Sci. 1995;40:86–95.
    12. Clouse RE. Antidepressants for irritable bowel syndrome. Gut. 2003 April; 52(4): 598–599.
    13. Greenbaum DS, Mayle JE, Vanegeren LE, et al. The effects of desipramine on IBS compared with atropine and placebo. Dig Dis Sci. 1987;32:257–266.
    14. Broekaert D, Vos R, Gevers AM, et al. A double-blind randomised placebo-controlled crossover trial of citalopram, a selective 5-hydroxytryptamine reuptake inhibitor, in irritable bowel syndrome). Gastroenterology. 2001;120:A641.
    15. Cui S, Hu Y. Multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Int J Clin Exp Med. 2012;5(3):238-244.
    16. Clarke G, Cryan JF, Dinan TG, Quigley EM. Review article: probiotics for the treatment of irritable bowel syndrome–focus on lactic acid bacteria. Aliment Pharmacol Ther. 2012 Feb;35(4):403-413.
    17. Johannesson E, Simrén M, Strid H, et al. Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2011 May;106(5):915-922.
    18. Camilleri M, Tack JF. Current medical treatments of dyspepsia and irritable bowel syndrome. Gastroenterol Clin North Am. 2010 Sep;39(3):481-493.
    19. FDA. Zelnorm ((tegaserod maleate)/ Postmarket drug safety information for patients and providers http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm103223.htm
    20. Olden KW. The use of antidepressants in functional gastrointestinal disorders – new uses for old drugs. CNS Spectr. 2005;10(11):891-897.
    21. Gorard DA, Libby GW, Farthing MJG. Effect of a tricyclic antidepressant on small intestinal motility in health and diarrhea-predominant irritable bowel syndrome. Dig Dis Sci. 1995;40:86–95.
    22. Clouse RE. Antidepressants for irritable bowel syndrome. Gut. 2003 April; 52(4): 598–599.
    23. Greenbaum DS, Mayle JE, Vanegeren LE, et al. The effects of desipramine on IBS compared with atropine and placebo. Dig Dis Sci. 1987;32:257–266.
    24. Broekaert D, Vos R, Gevers AM, et al. A double-blind randomised placebo-controlled crossover trial of citalopram, a selective 5-hydroxytryptamine reuptake inhibitor, in irritable bowel syndrome). Gastroenterology. 2001;120:A641.
    25. Cui S, Hu Y. Multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Int J Clin Exp Med. 2012;5(3):238-244.
    26. Clarke G, Cryan JF, Dinan TG, Quigley EM. Review article: probiotics for the treatment of irritable bowel syndrome–focus on lactic acid bacteria. Aliment Pharmacol Ther. 2012 Feb;35(4):403-413.
    27. Johannesson E, Simrén M, Strid H, et al. Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2011 May;106(5):915-922.
    28. FDA. FDA approves Linzess to treat certain cases of irritable bowel syndrome and constipation.  August 30, 2012. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm317505.htm