US Pharm. 2023;48(4):21-23.

Irritable bowel syndrome (IBS) is a common disorder affecting the stomach and intestines and is characterized by recurrent abdominal pain or discomfort and altered bowel habits. IBS is generally a long-term condition, with a significant disease burden and symptoms severe enough to impact daily living and social activities. IBS is a functional, nonstructural bowel disorder, and patients should be assessed to ensure that their symptoms are not part of a life-threatening illness.^1,2

IBS presents in distinct subtypes: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), IBS with mixed stool patterns (IBS-M), and IBS without abnormal stool patterns (IBS-U or unsubtyped). IBS is more common in women than in men, and it is more often diagnosed in persons aged 15 to 45 years. The American Gastroenterology Association (AGA) has updated its guideline recommendations for the treatment of IBS with all of the subtypes.^1,3

The prevalence of IBS among adults is estimated to be 4.1% to 10% globally, with IBS-C accounting for more than one-third of cases. Only a small number of people with IBS have severe symptoms; milder symptoms can be controlled by managing diet, lifestyle, and stress. More severe symptoms can be treated with medication and counseling.^2,3

IBS negatively impacts daily functioning, including increased absenteeism and inability to participate in social gatherings. Approximately 40% to 60% of patients with IBS have a comorbid psychological disorder (e.g., depression or anxiety) or comorbid insomnia.^1,4

IBS places a significant economic burden on the healthcare system, with high resource utilization resulting in direct medical costs of approximately $1.5 billion to $10 billion per year.⁵

Symptoms

Symptoms of IBS vary but are usually present for a long time. The most common symptoms include cramping, abdominal pain, bloating, gas, diarrhea or constipation, changes in appearance of bowel movement, and changes in how often patients have bowel movements. Other symptoms that are often related include sensation of incomplete evacuation and increased gas or mucus in the stool.^1,6

Symptoms of IBS can be triggered by food. The role of food allergy or intolerance in IBS is not fully understood. A true food allergy rarely causes IBS, but many people have worse IBS symptoms when they eat or drink certain foods or beverages. These include wheat, dairy products, citrus fruits, beans, cabbage, milk, and carbonated drinks. Most people with IBS experience worse or more frequent symptoms during periods of increased stress.^2,6

If patients have a persistent change in bowel habits or symptoms other than IBS, such as weight loss, diarrhea at night, rectal bleeding, iron deficiency anemia, unexplained vomiting, and pain that is not relieved by passing gas or a bowel movement, they should see a clinician as soon as possible to evaluate for an alternative condition.^2,6

Causes

The exact mechanism underlying IBS pathogenesis is not fully understood, but IBS is proposed to be a multifactorial disorder of the gut-brain axis. The gut-brain axis is described as bidirectional communication between the enteric nervous system and the central nervous system through neurohormonal, immune, and neuroendocrine pathways. Factors that appear to play a role in IBS include muscle contractions in the intestine, issues with the nerves in the nervous system, severe infection, early adulthood life stress, and changes in the gut microbiome.^1,2

Risk Factors

Many people have occasional symptoms of IBS. These may be due to some risk factors for IBS: people aged younger than 50 years, females especially in the United States, women with estrogen therapy before or after menopause, prior gastroenteritis, stress, and people with a family history of IBS or a predisposition to IBS.^1,7

IBS is also associated with poor quality of life and mood disorders. Experiencing the symptoms of IBS can lead to depression or anxiety. Depression and anxiety, in turn, can also worsen IBS.⁷

Diagnosis

There is no gold standard or test to definitively diagnose IBS. The healthcare provider is likely to start with a complete medical history, physical examination, and tests to rule out other conditions, such as celiac disease or inflammatory bowel disease.⁸ After other conditions have been ruled out, the provider will use the following set of diagnostic criteria for IBS.

Rome Criteria

The Rome criteria are a set of criteria used by clinicians to classify a diagnosis of a patient with functional gastrointestinal disorders (FGIDs). FGIDs account for at least 40% of all referrals to gastroenterologists. Of the 33 recognized adult FGIDs, IBS is the most prevalent, with a worldwide prevalence estimated at 12%. The Rome criteria are updated every 6 to 10 years. These criteria include belly pain and discomfort averaging at least 1 day a week within the past 3 months. This must also occur with at least two of the following: pain and discomfort related to defecation, a change in the frequency of defecation, or a change in stool consistency.^8,9

Treatment

For many years, the treatment of IBS has taken an approach involving the use of agents that regulate bowel function, such as laxatives or antidiarrheals, in addition to drugs that relieve symptomatic pain of visceral hypersensitivity (i.e., antispasmodics, antidepressants).^1,2 New advances in drug therapy have expanded the therapeutic spectrum for IBS to medications that target global symptom improvement. In 2022, the AGA updated its clinical practice guidelines on the pharmacologic treatment of IBS-C and IBS-D and incorporated some novel agents for management. As of now, no approved therapies are available for IBS-M or IBS-U.^1,10

IBS-C

To date, five pharmacologic agents have been FDA approved for IBS-C: linaclotide, plecanatide, lubiprostone, tegaserod, and tenapanor. Linaclotide works by two different mechanisms: reducing visceral hypersensitivity and increasing GI motility. The AGA guideline strongly recommends the use of linaclotide and conditionally recommends the use of plecanatide, tegaserod, lubiprostone, and tenapanor. With these, symptomatic therapy with antidepressants, laxatives, and antispasmodics may also be considered. The treatment guidelines emphasize the importance of tailoring treatment to patient-specific factors such as cost, adherence, and potential for side effects.^2-10

IBS-D

Symptomatic Treatment of IBS-D: Due to the limited number of drugs marketed specifically for IBS-D, other medications are often used to treat symptoms. They include loperamide, bile acid binders (e.g., cholestyramine), antidepressants, and probiotics.^10,11

Eluxadoline: This agent is a mixed mu– and kappa–opioid receptor agonist that reduces gastric peristalsis and delays transit time. Its limited systemic absorption restricts its effects selectively to the GI tract.^1,11

Rifaximin: Rifaximin is a nonabsorbable oral antibiotic whose mechanism for IBS-D remains incompletely understood, but its benefit is thought to derive from modulation of the gut microbiome and reduction of intestinal inflammation.¹¹

Alosetron: This selective 5-HT3 antagonist modulates central and peripheral neurotransmission to block visceral pain sensations and reduce gastric motility. Alosetron was originally FDA approved in 2000; however, it was voluntarily withdrawn from the market based on reports of ischemic colitis and serious constipation requiring hospitalization or surgery.¹¹ The drug was reintroduced in 2002 with a black box warning for ischemic colitis, and its use is limited to women with severe IBS-D after failure of conventional therapies.¹¹

Type of IBS

For the purpose of treatment, IBS can be divided into four types, based on the symptoms: constipation-predominant, diarrhea-predominant, mixed, or unclassified.¹

If an initial treatment for IBS fails, the provider will recommend additional tests, including stool studies to check for infection and malnutrition. Additional imaging and laboratory tests may be recommended, such as a colonoscopy, CT scan, and upper endoscopy to rule out other causes. Laboratory tests include lactose intolerance tests, breath tests for bacterial overgrowth, and stool tests.^1,2

As the root cause of IBS remains unknown, the ultimate goal is to gain a deeper understanding of the underlying mechanisms that trigger the syndrome. The hope is that this knowledge will lead to the development of more effective treatment options for individuals diagnosed with IBS, although progress toward this goal has been limited thus far.

Pharmacists’ Role in IBS Management

Pharmacists can play an integral role by educating patients about the importance of lifestyle and dietary modifications. Patients who are prescribed pharmacologic agents for IBS should be counseled on how to monitor for drug-related adverse effects. If extreme changes in bowel movements occur with IBS-D and IBS-C, patients should contact their physician immediately.

Patient adherence to treatment is critical for improving IBS symptoms, and pharmacists can assist in patients’ treatment based on cost, adherence, and treatment-related adverse effects. Pharmacists can also screen patients for contraindications or drug interactions related to IBS therapy. Pharmacists have a major role as healthcare providers for optimizing care and improving outcomes in patients with IBS.

REFERENCES

1. Barlow B. Update on the management of irritable bowel syndrome. US Pharm. 2022;47(12):48-55.
2. Mayo Clinic. Current and future treatments for irritable bowel syndrome associated with di-arrhea. September 5, 2015. www.mayoclinic.org/medical-professionals/digestive-diseases/news/current-and-future-treatments-for-ibs-d/mac-20429499. Accessed March 9, 2023.
3. Enck P, Aziz Q, Barbara G, et al. Irritable bowel syndrome. Nat Rev Dis Primers. 2016;2:16014.
4. Hu Z, Li M, Yao L, et al. The level and prevalence of depression and anxiety among patients with different subtypes of irritable bowel syndrome: a network meta-analysis. BMC Gastroen-terol. 2021;21(1):23-28.
5. Canavan C, West J, Card T. Review article: the economic impact of the irritable bowel syn-drome. Aliment Pharmacol Ther. 2014;40(9):1023-1034.
6. Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: management of irritable bowel syndrome. Am J Gastroenterol. 2021;116(1):17-44.
7. Saha L. Irritable bowel syndrome: pathogenesis, diagnosis, treatment, and evidence-based medicine. World J Gastroenterol. 2014;20(22):6759-6773.
8. Lacy BE, Patel NK. Rome criteria and a diagnostic approach to irritable bowel syndrome. J Clin Med. 2017;6(11):99.
9. Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide prevalence and burden of func-tional gastrointestinal disorders, results of Rome Foundation global study. Gastroenterolo-gy. 2021;160(1):99-114.e3.
10. Chang L, Sultan S, Lembo A, et al. AGA clinical practice guideline on the pharmacological management of irritable bowel syndrome with constipation. Gastroenterology. 2022;163(1):118-136.
11. Lembo A, Sultan S, Chang L, et al. AGA clinical practice guideline on the pharmacological management of irritable bowel syndrome with diarrhea. Gastroenterology. 2022;163(1):137-151.

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