Irritable Bowel Syndrome Causes and Treatment

Symptoms

Irritable bowel syndrome is a functional bowel disorder that manifests itself in the following persistent or recurrent symptoms:

• Lower abdominal pain or cramping
• Diarrhea and/or constipation
• Flatulence
• Change in bowel habits, impaired defecation.
• Incontinence, urge to defecate, feeling of incomplete emptying.

The symptoms improve with defecation. Some patients suffer mainly from diarrhea, others from constipation. Also a change between diarrhea and constipation occurs, resp. a mixed type (IBS: Irritable Bowel Syndrome):

• IBS-D Diarrhea: predominantly diarrhea.
• IBS-C Constipation: predominantly constipation.
• IBS-M Mixed: diarrhea and constipation.
• IBS-A Alternating : diarrhea and constipation alternating.

The syndrome often begins in childhood and may disappear on its own after some time. Data on prevalence vary, but what is certain is that large segments of the population are affected. The symptoms can be a strong psychosocial burden in everyday life and professional life and lead to anxiety, depression and frustration.

Causes

Irritable bowel syndrome is referred to as “functional” because no organic (structural) causes can be identified. Visceral hypersensitivity and psychological factors are considered to be established mechanisms of development. Motility disorders also play a role. In some patients, viral or bacterial gastroenteritis precedes, for example, traveler’s diarrhea (so-called postinfectious irritable bowel syndrome).

Risk factors

• Women are more often affected, worsening during menstruation.
• Psychological stress
• Psychosocial factors, personality
• Heredity
• History of gastroenteritis
• Certain foods and stimulants such as caffeine, the FODMAP, citrus fruits, grains, wheat and gluten can trigger or worsen symptoms.

Diagnosis

The diagnosis can be made in medical treatment usually based on a thorough history, physical examination and with some laboratory tests. In the presence of alarm symptoms such as rectal bleeding, anemia, weight loss, fever, family history of colon cancer, or onset at an age older than 50 years, further testing is necessary to rule out other causes. Differential diagnoses are numerous, as many diseases, conditions, and medications can trigger constipation and diarrhea.

Nonpharmacologic treatment

Methods such as psychotherapy, hypnosis, cognitive behavioral therapy, psychodynamic therapy, relaxation techniques, and attending support groups can positively influence the course of the disease. Food: Possible triggers should be identified and avoided or reduced. Dietary fiber and bulking agents have a beneficial effect. FODMAP is the name given to a group of carbohydrates and sugar alcohols that can cause digestive disturbances such as a diarrhea, flatulence, abdominal pain and cramps in sensitive people. These include fructans, galactooligosaccharides, lactose, fructose and polyols such as sorbitol and mannitol. Diets low in FODMAPs can relieve IBS symptoms. It should be noted, however, that FODMAPs are not unhealthy per se and also exert beneficial effects in the intestine.

Drug treatment

Drug therapy is individualized to each patient. A single medication is usually not sufficient, and it is necessary to try what is most effective and tolerated. Antidiarrheal agents:

• Like loperamide help to treat diarrhea. Loperamide is approved to treat chronic diarrhea but should be used cautiously. It is also taken by patients as a preventive measure. Herbal remedies such as black tea (steep for 10 minutes), charcoal, blueberries, raspberry and blackberry leaves can also be tried. Eluxadoline (Truberzi) was newly approved in the EU in 2016 and in many countries in 2018.

Laxatives:

• Help with constipation. Since it is a chronic disorder, longer-term well-tolerated means should be selected, such as swelling agents (fiber such as psyllium, Indian psyllium, wheat bran) or osmotic laxatives.Stimulant laxatives such as Senna or bisacodyl are less well tolerated with prolonged use and should be used cautiously. Caution: some laxatives can cause flatulence as an adverse effect.

Anti-flatulent agents:

• Such as the antifoaming agents simeticone and dimeticone or various herbal remedies (peppermint, anise, fennel, caraway) are used against flatulence. They are usually well tolerated.

Digestive enzymes:

• Enzymes such as pancreatin, the lactase, the xylose isomerase and the alpha-galactosidase can increase the tolerance of foods that trigger or aggravate the symptoms.

Herbal medications:

• Peppermint oil capsules are effective against flatulence and pain according to small studies. Colpermin is approved in many countries in the indication of irritable bowel syndrome. Iberogast, which contains various herbal extracts, is also approved in the indication irritable stomach and irritable bowel. According to the manufacturer, it has an antispasmodic, prokinetic and analgesic effect.

Probiotics:

• Such as Lactobacillus plantarum 299v (Vitafor probi-intestis) support the intestinal flora and act against flatulence and abdominal pain.

Antispasmodic agents:

• Such as metixene, scopolamine butylbromide, or mebeverine can help with spasms and abdominal pain. Parasympatholytics may cause adverse effects such as fatigue, visual disturbances, and urinary retention.

Tricyclic antidepressants:

• Such as amitriptyline can improve pain symptoms and psychological comorbidities. They may also be effective against diarrhea because of their anticholinergic effects and have potentially numerous adverse effects. SSRIs such as fluoxetine, paroxetine, and citalopram are also used.

Prokinetics:

• Trimebutine acts on opioid receptors and is approved in many countries for the treatment of irritable bowel syndrome.

Other options

Alternative medicine:

• E.g. Traditional Chinese Medicine

5-HT3 antagonists:

• Are not commercially available in many countries. Alosetron is approved in the United States as a backup medication for women with IBS-D (diarrhea type) (Lotronex). Its use has been restricted because of adverse effects such as constipation and colonic ischemia. Other agents in this group include cilansetron and ramosetron.

Chloride channel activators:

• Lubiprostone (Amitiza) has been approved in the United States for the treatment of chronic constipation and IBS-C (constipation type). It acts on chloride channels at the mucosa, promoting secretion of electrolyte-rich fluid into the intestine and thus increasing motility. It was also approved in many countries in late 2009 for the treatment of chronic idiopathic constipation (but not irritable bowel syndrome).

Guanylate cyclase C agonists:

• Linaclotide is a guanylate cyclase-C agonist and also promotes the secretion of chloride and bicarbonate into the intestine.

NHE3 inhibitors:

• Such as tenapanor inhibit sodium/hydrogen exchanger 3 (NHE3) and retain sodium and water in the intestine. As a result, they soften stool and promote bowel motility. Tenapanor has additionally demonstrated antinociceptive properties.

5-HT4 agonists:

• Such as tegaserod (Zelmac, off label) have been used to treat IBS-C (constipation type). They have a prokinetic effect and stimulate intestinal secretion of water and chloride. Diarrhea may occur as an adverse effect. After an increased risk of ischemic cardiovascular events such as myocardial infarction and stroke was shown with tegaserod, Novartis withdrew the drug from the market in many countries on orders from Swissmedic.

Non-absorbable antibiotics:

• Such as rifaximin are used to treat flatulence, but are not commercially available in many countries.

Placebo:

• Many studies have shown high placebo effects, even when patients were informed that they were receiving placebo.

Numerous other agents are in clinical development and investigation but not yet commercially available or approved for this indication.