irritable%20bowel%20syndrome
IRRITABLE BOWEL SYNDROME
Irritable bowel syndrome is a common chronic gastrointestinal condition characterized by abdominal pain and bloating with altered bowel habits.
There are no identifiable physical, radiologic or lab abnormalities indicative of organic disease.
Symptoms may be exacerbated by stress, alcohol or food.

Principles of Therapy

  • The cornerstone of IBS therapy is a strong physician-patient relationship, education and reassurance which may reduce the need for further consultation and may be therapeutic
Establishing Therapeutic Relationship
  • Listening to patient: Address concerns, identify and discuss patient’s beliefs
  • Explaining the disease state: Nature, causes, aggravating factors and prognosis
  • Reassuring patient of the benign nature of IBS

General Therapeutic Principles for Pharmacotherapy in IBS
  • Goal of therapy is to improve global IBS symptoms which include abdominal discomfort/bloating and altered bowel habits
    • Not only should therapy be directed at altered bowel habits (eg constipation, diarrhea, fecal urgency) but should also address abdominal discomfort
  • Therapy should be given to those in whom there is an impact on quality of life from IBS symptoms
Symptom-Based Descriptions
  • IBS symptoms may fluctuate over time and vary between individuals
    • IBS with constipation often changes to constipation alone or IBS alternating between constipation and diarrhea without any other functional GI disorders over time
  • Therefore, symptom-based descriptions may be used to guide management (eg IBS with diarrhea or IBS with constipation)

Pharmacotherapy

A. Pharmacotherapy for IBS with Constipation (IBS-C)

Bulk-Producing Laxatives
  • Eg Ispaghula (Psyllium), Methylcellulose, Polycarbophil
  • Ispaghula husk may increase frequency of bowel movements in IBS patients with constipation
  • Bulk-producing laxatives (wheat/corn bran) have not been found to improve global IBS symptoms compared to placebo
  • Patients with constipation should first attempt to increase fiber in their diet; if this does not improve symptoms, then addition of Ispaghula may be tried
    • Polycarbophil or Methylcellulose may be better tolerated if Ispaghula is not tolerated
  • Patients should be warned that bloating and abdominal distension may occur especially at the start of fiber therapy but may decrease over time or with a dose reduction
  • Fiber products are appropriate for treatment of constipation but may not be recommended for treatment of IBS because of the increase in bloating and abdominal discomfort they can cause

Guanylate Cyclase Receptor Agonists

Linaclotide

  • Recommended for patients with moderate to severe IBS-C and also for overall symptom improvement
  • Increases intracellular and extracellular cyclic guanosine monophosphate (cGMP) concentrations resulting in secretion of chloride and bicarbonate into the intestinal lumen increasing intestinal fluid and decreasing GI transit time, and modulates afferent pain sensors
  • Randomized controlled trials showed improvement in global symptoms of IBS

Plecanatide

  • Recommended for overall symptom improvement in patients with IBS-C
  • Stimulates electrolyte and fluid transport into the lumen
Osmotic Laxatives
  • Eg Milk of Magnesia, Sorbitol, Magnesium citrate, polyethylene glycol (PEG)
  • If dietary fiber and bulk-producing laxatives are not effective, then osmotic laxatives may be tried though there are no published studies with these laxatives in IBS-C patients and should not be given to patients with renal dysfunction
  • PEG is not recommended for overall symptom improvement in patients with IBS
    • Improves frequency of bowel movement but not pain and other symptoms of IBS
Other Laxatives
  • Eg Lubiprostone
  • Recent studies concluded that Lubiprostone is an effective C-2 chloride channel activator for relief of IBS symptoms in women (ie abdominal pain, straining, constipation severity)
Serotonin 5-HT4 Receptor Agonists

Tegaserod
  • Has been shown to be more effective than placebo at relieving global IBS symptoms in females with IBS-C and IBS-M
  • Withdrawn from the market due to cardiovascular side effects

Prucalopride

  • A prokinetic that has been shown in clinical trials to be effective for chronic constipation
    • An alternative to patients unresponsive to conventional laxatives
  • Further studies in patients with IBS-C are needed to confirm efficacy and safety
Other Drug for Constipation

Probiotic

  • Benefits patients with IBS via multiple mechanisms 
  • A meta-analysis showed benefits for global symptoms of IBS 
  • Bifidobacterium lactis, a probiotic strain, has shown to accelerate GI transit and increase stool frequency among IBS-C patients 
B. Pharmacotherapy for IBS with Diarrhea (IBS-D)

Antidiarrheals

Synthetic Opiates
  • Eg Diphenoxylate/atropine, Eluxadoline and Loperamide
  • May be used in patients suffering from diarrhea as they can reduce loose stools, urgency and fecal soiling
  • Loperamide
    • Significantly improves diarrheal symptoms in patients with IBS but is not recommended for continuous use due to lack of significant overall symptom improvement in IBS patients 
  • Eluxadoline
    • Mu- and kappa-opioid receptor agonist, and delta-opioid receptor antagonist in the enteric nervous system
    • May be considered for overall symptom improvement in patients with IBS-D
    • Contraindicated in patients with history of alcohol abuse/addiction, biliary duct obstruction, pancreatitis, severe liver problems and patients who underwent cholecystectomy due to increased risk of pancreatitis
Cholestyramine
  • May be considered in a subgroup of IBS patients with diarrhea secondary to cholecystectomy or bile acid malabsorption
Antibiotic
  • Rifaximin may be used for the treatment of abdominal pain and diarrhea in patients with IBS-D
  • Consider evaluating for a severe infectious diarrhea eg C difficile enterocolitis, if diarrhea does not improve or worsens following treatment with Rifaximin
Serotonin 5-HT3 Receptor Antagonists

Alosetron
  • Has been shown to be more effective than placebo at relieving global IBS symptoms in female IBS patients with diarrhea
  • United States Food and Drug Administration (USFDA) approval only for use in women with severe diarrhea-predominant IBS who have failed to respond to conventional IBS therapy
  • Action: Decreases gut transit in non-IBS and IBS patients
    • Enhances basal sodium and fluid absorption
    • Relaxes the left colon thereby reducing the perception of fluid distension in patients with IBS
  • Cases of ischemic colitis and serious constipation complications have occurred with the use of Alosetron; therefore, the patient and physician need to carefully consider risk/benefit profile before deciding to use

Ondansetron

  • Found to be helpful in improving urgency, diarrhea and bloating in IBS-D
Ramosetron
  • A promising therapeutic agent for patients with IBS-D; a study demonstrated higher rates of relief of overall IBS symptoms in male patients with IBS-D than placebo
  • Action: Inhibits 5-HT3 receptor antagonism in the vagal afferent neurons and myenteric plexus
  • Trials show incidence of constipation is lower among patients treated with Ramosetron and no ischemic colitis was reported
C. Pharmacotherapy for Abdominal Pain, Bloating

Antibiotics
  • Some clinical trials have shown that a nonabsorbable antibiotic, Rifaximin, is more effective for global improvement of IBS and bloating as compared to placebo
  • No studies are available to support long-term use of antibiotics for the management of IBS
  • There are not enough available evidence to support the use of Neomycin, Metronidazole, and Clarithromycin for improvement of symptoms of IBS
Antispasmodics
  • May be considered for pain/bloating especially when exacerbated by meals
  • The smooth muscle relaxants, Cimetropium, Hyoscine, Mebeverine, Octylonium bromide (Otilonium Br), Pinaverium bromide, Trimebutine, and Peppermint oil may be more effective than placebo
  • Best used on a short-term, as-needed basis, up to 3x/day for acute attacks of pain or before meals if there are postprandial symptoms
  • Adverse effects may limit their usefulness
Tricyclic Antidepressants (TCAs)
  • Though not an approved indication, low-dose TCAs may be considered for severe IBS in which pain is more constant or disabling
  • TCAs have been shown to significantly improve abdominal pain and symptoms in IBS patients compared with placebo
    • Relieve abdominal pain associated with IBS independent of their effect on mood
    • May be more effective in IBS-D
  • Action: Effect may be due to a reduction in the sensitivity of peripheral nerves or to alterations in the brain
Selective Serotonin Reuptake Inhibitors (SSRIs)
  • SSRIs have been shown to be more effective than placebo at relieving global IBS symptoms
  • Also proven to reduce abdominal pain greatly in IBS-C
  • Recommended only when there is treatment failure after TCA therapy
  • Advise patients to strictly follow up after 4 weeks and every 6-12 months while on SSRI therapy

Non-Pharmacological Therapy

Behavioral Therapy
  • Identify signs of a psychological disorder as psychological disorders and IBS are often comorbid conditions
  • Psychological treatments that have been used:
    • Relaxation therapy, biofeedback, hypnotherapy, cognitive therapy and psychotherapy
  • Various clinical trials have shown that cognitive behavioral therapy, dynamic psychotherapy and hypnotherapy are beneficial for IBS patients except relaxation therapy
  • Cognitive behavioral therapy has been found to be more effective than placebo in relieving individual IBS symptoms
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