IRRITABLE BOWEL SYNDROME

Drug therapy should target main symptoms and possible psychiatric comorbidities

. Combinations of drugs may be required for maximal effectiveness. a. Antispasmodics: Used mostly for short-term relief of abdominal pain but may also treat diarrhea in patients with IBS-D. May be used on an as-needed or scheduled basis i. Dicyclomine (Bentyl): Anticholinergic adverse effects ii. Hyoscyamine (Levsin, Levsin SL), anticholinergic adverse effects iii. Peppermint oil: Use enteric-coated products; may worsen GERD b. Tricyclic antidepressants: Treat pain, improve global symptoms, and slow motility in patient with IBS-D. Can be used in IBS-C but may worsen constipation i. Amitriptyline, nortriptyline, and imipramine are the most studied. ii. Doses cannot be raised high enough to treat comorbid depression. iii. Potential for anticholinergic effects, sedation, CV effects, and drug interactions c. Selective serotonin reuptake inhibitors (SSRIs): Treat pain and improve global symptoms similar to tricyclic antidepressants. Used for both IBS-D and IBS-C i. Fluoxetine, sertraline, citalopram, and paroxetine are all viable options. ii. Tend to have a prokinetic effect, so may also improve constipation in IBS-C; however, can also use in IBS-D, especially if comorbid depression or anxiety exists iii. Adverse effects include insomnia, sexual dysfunction, and withdrawal. d. Laxatives: Used for IBS-C i. Psyllium has best evidence; however, it may cause bloating and gas formation. Calcium polycarbophil may be used as an alternative bulk-forming agent, Wheat or corn bran should not be used. ii. PEG-based laxatives (MiraLAX) may increase stool frequency, but they have fewer effects on reductions in abdominal pain. Minimal to no bloating iii. Avoid stimulant laxatives because they may worsen abdominal pain. e. Lubiprostone: FDA approved for IBS-C in women older than 18 years i. Chloride channel activator; improves motility and possibly pain ii. Dose is 8 mcg twice daily with meals for IBS-C. iii. Nausea and diarrhea are main adverse effects, costly as well f. Tegaserod (Zelnorm): 5HT4 partial agonist FDA approved for IBS-C i. Improves pain, global symptoms, and motility ii. Available on an emergency-use basis only because of its association with the development of CV events in women g. Alosetron (Lotronex): 5HT3 antagonist that is FDA approved for IBS-D i. Improves global symptoms and reduces motility ii. Associated with the development of colonic ischemia, so available only through manufacturer prescribing program h. Loperamide i. No effects on global symptoms or pain, but reduces motility and increases stool consistency. May be used as an adjunct to other therapies in IBS-D i. Probiotics: Some evidence to support improvement of global symptoms i. Lactobacilli given alone do not appear to be effective. ii. Bifidobacteria appears to be most efficacious. Combinations of bifidobacteria and other probiotic agents can also be used. j. Antibiotics: A short course (10-14 days) of nonabsorbable antibiotic may improve global symptoms of IBS, especially bloating. i. Rifaximin 400 mg 2 or 3 times/day for 10-14 days has shown some efficacy. This agent is expensive and does not have an FDA-approved indication for IBS. ii. Limited data with neomycin and metronidazole

Definition and Pathophysiology

1. IBS is considered a functional GI disorder. The ACG 2009 guidelines define it as "abdominal pain or discomfort that occurs in association with altered bowel habits over a period of at least 3 months." 2. Definition divides IBS into the following subtypes: a. Diarrhea predominant (IBS-D) b. Constipation predominant (IBS-C) c. Mixed IBS (IBS-M): Features of both IBS-D and IBS-C 3. The pathophysiology is thought to involve alterations in both CNS and intestinal pain perception, alterations in GI motility and secretion, and contributions from current or past psychosocial factors, gas retention, and possibly previous GI infection or bacterial overgrowth. a. IBS more common in women, in individuals in lower socioeconomic groups, and in patients younger than 50 years. b. Patients experience significant reductions in quality of life and use more health care resources. c. Comorbid psychiatric illnesses such as depression and anxiety may be present in a significant percentage of patients. 4. Symptoms: In addition to diarrhea or constipation, pain is often a component of all subtypes. Other symptoms such as bloating, distention, spasm, or urgency may be present as well.

Treatment Strategies

1. Treatment involves a mix of drug, diet, and psychosocial interventions. Cognitive behavioral therapy, dynamic psychotherapy, and hypnotherapy have all shown effectiveness in IBS. 2. Dietary intervention involves avoidance of foods that trigger symptoms. 3. Drug therapy should target main symptoms and possible psychiatric comorbidities. Combinations of drugs may be required for maximal effectiveness. a. Antispasmodics: Used mostly for short-term relief of abdominal pain but may also treat diarrhea in patients with IBS-D. May be used on an as-needed or scheduled basis i. Dicyclomine (Bentyl): Anticholinergic adverse effects ii. Hyoscyamine (Levsin, Levsin SL), anticholinergic adverse effects iii. Peppermint oil: Use enteric-coated products; may worsen GERD b. Tricyclic antidepressants: Treat pain, improve global symptoms, and slow motility in patient with IBS-D. Can be used in IBS-C but may worsen constipation i. Amitriptyline, nortriptyline, and imipramine are the most studied. ii. Doses cannot be raised high enough to treat comorbid depression. iii. Potential for anticholinergic effects, sedation, CV effects, and drug interactions c. Selective serotonin reuptake inhibitors (SSRIs): Treat pain and improve global symptoms similar to tricyclic antidepressants. Used for both IBS-D and IBS-C i. Fluoxetine, sertraline, citalopram, and paroxetine are all viable options. ii. Tend to have a prokinetic effect, so may also improve constipation in IBS-C; however, can also use in IBS-D, especially if comorbid depression or anxiety exists iii. Adverse effects include insomnia, sexual dysfunction, and withdrawal. d. Laxatives: Used for IBS-C i. Psyllium has best evidence; however, it may cause bloating and gas formation. Calcium polycarbophil may be used as an alternative bulk-forming agent, Wheat or corn bran should not be used. ii. PEG-based laxatives (MiraLAX) may increase stool frequency, but they have fewer effects on reductions in abdominal pain. Minimal to no bloating iii. Avoid stimulant laxatives because they may worsen abdominal pain. e. Lubiprostone: FDA approved for IBS-C in women older than 18 years i. Chloride channel activator; improves motility and possibly pain ii. Dose is 8 mcg twice daily with meals for IBS-C. iii. Nausea and diarrhea are main adverse effects, costly as well f. Tegaserod (Zelnorm): 5HT4 partial agonist FDA approved for IBS-C i. Improves pain, global symptoms, and motility ii. Available on an emergency-use basis only because of its association with the development of CV events in women g. Alosetron (Lotronex): 5HT3 antagonist that is FDA approved for IBS-D i. Improves global symptoms and reduces motility ii. Associated with the development of colonic ischemia, so available only through manufacturer prescribing program h. Loperamide i. No effects on global symptoms or pain, but reduces motility and increases stool consistency. May be used as an adjunct to other therapies in IBS-D i. Probiotics: Some evidence to support improvement of global symptoms i. Lactobacilli given alone do not appear to be effective. ii. Bifidobacteria appears to be most efficacious. Combinations of bifidobacteria and other probiotic agents can also be used. j. Antibiotics: A short course (10-14 days) of nonabsorbable antibiotic may improve global symptoms of IBS, especially bloating. i. Rifaximin 400 mg 2 or 3 times/day for 10-14 days has shown some efficacy. This agent is expensive and does not have an FDA-approved indication for IBS. ii. Limited data with neomycin and metronidazole

Diagnosis

1. Typically a diagnosis of exclusion. Need to rule out other GI causes with thorough work-up. Evaluation of patient's pattern of symptoms may provide insight regarding subtype, although patients may alternate between forms. 2. Several diagnostic criteria and scoring systems have been developed including the Kruis, Manning, and Rome criteria (see guidelines). These criteria are generally inaccurate and include different variables. They are used mainly in the research setting. a. Guidelines recommend if other GI diseases are excluded and no alarm features (weight loss, bleeding, anemia, etc.) are present, then diagnosis of IBS can be made with confidence b. The ACG guidelines also recommend: i. Screening for celiac disease in patients with IBS-D and IBS-M ii. No endoscopy if younger than 50 years and no alarm symptoms iii. No routine food allergy testing iv. No routine checking for small intestinal bacterial overgrowth unless lactose intolerance is a concern despite dietary intervention

Alosetron (Lotronex):

5HT3 antagonist that is FDA approved for IBS-D i. Improves global symptoms and reduces motility ii. Associated with the development of colonic ischemia, so available only through manufacturer prescribing program

Tegaserod (Zelnorm):

5HT4 partial agonist FDA approved for IBS-C i. Improves pain, global symptoms, and motility ii. Available on an emergency-use basis only because of its association with the development of CV events in women

Lubiprostone

: FDA approved for IBS-C in women older than 18 years i. Chloride channel activator; improves motility and possibly pain ii. Dose is 8 mcg twice daily with meals for IBS-C. iii. Nausea and diarrhea are main adverse effects, costly as well

Antispasmodics

: Used mostly for short-term relief of abdominal pain but may also treat diarrhea in patients with IBS-D. May be used on an as-needed or scheduled basis i. Dicyclomine (Bentyl): Anticholinergic adverse effects ii. Hyoscyamine (Levsin, Levsin SL), anticholinergic adverse effects iii. Peppermint oil: Use enteric-coated products; may worsen GERD

Antibiotics:

A short course (10-14 days) of nonabsorbable antibiotic may improve global symptoms of IBS, especially bloating. i. Rifaximin 400 mg 2 or 3 times/day for 10-14 days has shown some efficacy. This agent is expensive and does not have an FDA-approved indication for IBS. ii. Limited data with neomycin and metronidazole

Probiotics:

Some evidence to support improvement of global symptoms i. Lactobacilli given alone do not appear to be effective. ii. Bifidobacteria appears to be most efficacious. Combinations of bifidobacteria and other probiotic agents can also be used. g. Alosetron (Lotronex): 5HT3 antagonist that is FDA approved for IBS-D i. Improves global symptoms and reduces motility ii. Associated with the development of colonic ischemia, so available only through manufacturer prescribing program

Selective serotonin reuptake inhibitors (SSRIs):

Treat pain and improve global symptoms similar to tricyclic antidepressants. Used for both IBS-D and IBS-C i. Fluoxetine, sertraline, citalopram, and paroxetine are all viable options. ii. Tend to have a prokinetic effect, so may also improve constipation in IBS-C; however, can also use in IBS-D, especially if comorbid depression or anxiety exists iii. Adverse effects include insomnia, sexual dysfunction, and withdrawal.

Tricyclic antidepressants:

Treat pain, improve global symptoms, and slow motility in patient with IBS-D. Can be used in IBS-C but may worsen constipation i. Amitriptyline, nortriptyline, and imipramine are the most studied. ii. Doses cannot be raised high enough to treat comorbid depression. iii. Potential for anticholinergic effects, sedation, CV effects, and drug interactions

Laxatives:

Used for IBS-C i. Psyllium has best evidence; however, it may cause bloating and gas formation. Calcium polycarbophil may be used as an alternative bulk-forming agent, Wheat or corn bran should not be used. ii. PEG-based laxatives (MiraLAX) may increase stool frequency, but they have fewer effects on reductions in abdominal pain. Minimal to no bloating iii. Avoid stimulant laxatives because they may worsen abdominal pain.

Definition divides IBS into the following subtypes:

a. Diarrhea predominant (IBS-D) b. Constipation predominant (IBS-C) c. Mixed IBS (IBS-M): Features of both IBS-D and IBS-C

Several diagnostic criteria and scoring systems

have been developed including the Kruis, Manning, and Rome criteria (see guidelines). These criteria are generally inaccurate and include different variables. They are used mainly in the research setting. a. Guidelines recommend if other GI diseases are excluded and no alarm features (weight loss, bleeding, anemia, etc.) are present, then diagnosis of IBS can be made with confidence b. The ACG guidelines also recommend: i. Screening for celiac disease in patients with IBS-D and IBS-M ii. No endoscopy if younger than 50 years and no alarm symptoms iii. No routine food allergy testing iv. No routine checking for small intestinal bacterial overgrowth unless lactose intolerance is a concern despite dietary intervention

The ACG guidelines also recommend:

i. Screening for celiac disease in patients with IBS-D and IBS-M ii. No endoscopy if younger than 50 years and no alarm symptoms iii. No routine food allergy testing iv. No routine checking for small intestinal bacterial overgrowth unless lactose intolerance is a concern despite dietary intervention

The pathophysiology

is thought to involve alterations in both CNS and intestinal pain perception, alterations in GI motility and secretion, and contributions from current or past psychosocial factors, gas retention, and possibly previous GI infection or bacterial overgrowth. a. IBS more common in women, in individuals in lower socioeconomic groups, and in patients younger than 50 years. b. Patients experience significant reductions in quality of life and use more health care resources. c. Comorbid psychiatric illnesses such as depression and anxiety may be present in a significant percentage of patients.