Irritable%20bowel%20syndrome Treatment

• 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 or 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)

A. Pharmacological Therapy for IBS with Constipation (IBS-C) 

Bulk-Producing Laxatives 

• Eg Ispaghula (Psyllium), Methylcellulose, Polycarbophil
• 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
  • A few small studies conducted in older adults showed similar effectiveness of Polycarbophil and Methylcellulose to Ispaghula
• Ispaghula husk is moderately effective for constipation and is associated with an overall improvement in patients with IBS
• 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
• Wheat/corn bran have not been found to improve global IBS symptoms compared to placebo

Osmotic Laxatives

• Eg Lactulose, 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 improves frequency and consistency of bowel movement but not pain and other symptoms of IBS
  • Is widely available and has lesser side effects compared with Lactulose or Milk of Magnesia

Guanylate Cyclase-C Receptor Agonists

Linaclotide

• Recommended for patients with moderate to severe IBS-C and also for overall symptom improvement
  • Randomized controlled trials showed improvement in global symptoms of IBS

Plecanatide

• Recommended for overall symptom improvement in patients with IBS-C
• Has comparable efficacy and safety as Linaclotide

Type 2 Chloride Channel Agonist 

Lubiprostone

• Improves stool consistency and abdominal pain in women at 1 month of use and is better than placebo in improving abdominal bloating at 3 months
  • Initial response may be delayed but improvement in global symptoms is maintained or increases over time

Serotonin 5-HT₄ Receptor Agonists

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

Tegaserod

• Has been shown to be more effective than placebo at relieving global IBS symptoms in women with IBS-C and IBS-M
• An alternative agent in women <65 years old with ≤1 risk factor for cardiovascular (CV) disease and without a history of ischemic CV disease who have inadequately responded to secretagogues

Sodium/Hydrogen Exchanger 3 (NHE3) Inhibitor 

Tenapanor

• Clinical trials showed improvement in spontaneous bowel movements and abdominal pain when compared with placebo in patients with IBS-C 

B. Pharmacological Therapy 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

Bile Acid Sequestrants 

• Eg Cholestyramine, Colesevelam, Colestipol 
• May be considered in a subgroup of IBS patients with diarrhea secondary to cholecystectomy or bile acid malabsorption

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 (US FDA) approval only for use in women with severe diarrhea-predominant IBS for 6 months and who have failed to respond to conventional IBS therapy
• Decreases gut transit in non-IBS and IBS patients, enhances basal sodium and fluid absorption, and 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 stool consistency, urgency, and frequency 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
• 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

Antibiotic 

• Rifaximin is a safe and effective agent 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

C. Pharmacological Therapy for Abdominal Pain and Bloating 

Antispasmodics

• May be used in patients of all IBS subtypes for the treatment of abdominal pain and spasms 
  • May be considered for pain/bloating especially when exacerbated by meals
• The smooth muscle relaxants, Cimetropium, Hyoscine, Hyoscyamine, Dicyclomine, Mebeverine, Octylonium bromide (Otilonium Br), Pinaverium bromide, Trimebutine, and Peppermint oil may be more effective than placebo in improving IBS symptoms
• 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

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
• 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

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

Behavioral Therapy  

• Identify signs of a psychological disorder as psychological disorders and IBS are often comorbid conditions
• Consider administering psychological treatments in cases wherein a significant association between stress and symptoms exist or in patients who are unresponsive after 3-6 months of treatment with 1st- or 2nd-line agents
• Psychological treatments that have been used include 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