martes, 13 de agosto de 2019

Irritable Bowel Syndrome (IBS) Research

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By Dr. Ananya Mandal, MDReviewed by April Cashin-Garbutt, MA (Editor)

Most studies regarding Irritable Bowel Syndrome (IBS) have their limitations in having involved only a small number of patients and lacking complete understanding of factors that influence the disease outcome.

A better research into the following subjects is underway:

Definition of the disease natural history using large community based studies
Food intolerance in the IBS pathogenesis
Dietary manipulation in treatment of IBS
Assessment of psychological therapies for IBS and comparing the efficacy of tricyclic antidepressants (TCA) and selective serotonin uptake inhibitor (SSRI)
Studies to evaluate the benefits and cost effectiveness of behavioural interventions including patient education

Step-wise symptom based recommendation for positive diagnosis

A systematic approach to diagnosis has been devised after a thorough history and physical examination.

In the absence of other diseases (“red flags”), investigations are rarely required to confirm the diagnosis of IBS.

However, when red flags are suspected organic causes should be excluded with tests like colonoscopy, sigmoidoscopy, barium enema, and stool for blood etc.

Serotonergic agents in IBS

After the pathophysiology of IBS involving gut dysmotility, visceral hypersensitivity and intestinal secretion has been elucidated, pharmacological agents have been used to attenuate these mechanisms.

Serotonin (5-hydroxytryptamine, 5-HT) is one of the primary mediators affecting gut motility. Serotonergic agents are thus used for symptom management in IBS.

Tegaserod and Alosetron research

Tegaserod (Zelnorm), a 5-HT4 receptor agonist acquired FDA approval for treatment of constipation in women with IBS not very long ago.

Alosetron (Lotronex), 5-HT3 receptor antagonist is another drug with beneficial effects.

Studies involving these drugs have however shown comparable results with placebo as the chronic state of IBS have a waxing and waning characteristic over a period of time.

In 3 clinical trials evaluating the efficacy and safety of tegaserod in the treatment of patients with IBS with constipation, the number needed to treat (NNT) for tegaserod 6 mg twice daily was reported as 10. This meant that an average of 10 patients would need to be treated with tegaserod in order for 1 patient to achieve improvement over placebo.

An assessment of 6 alosetron clinical trials reported an overall NNT of 7.15, suggesting that on average 7 patients would need to be treated with alosetron in order for 1 patient to achieve improvement over placebo.

Renzapride research

Renzapride a 5-HT3 antagonist and 5-HT4 agonist has been found to have a positive outcome in IBS with constipation in phase 2 trials.

A study compared the efficacy and safety of renzapride 1 mg, 2 mg, or 4 mg versus placebo in 510 patients with constipation. Results demonstrated up to an 8.2% increase over placebo in patients’ weekly assessments of adequate relief of abdominal pain/discomfort as well as increased bowel movement frequency (2 mg and 4 mg) and improved stool consistency (softness, 4 mg). Side effects across all treatment groups occurred at a similar rate.

Cilansetron research

Cilansetron acts as a 5-HT3 receptor antagonist and has been found to control the symptoms of diarrhoea in IBS.

A study compared cilansetron 2mg thrice daily with placebo in patients of IBS with diarrhoea. 60% of patients reported an improvement after 6 months compared to 45% patients receiving placebo.

Constipation was the most common side effect (12% versus 3% in placebo group) and ischemic colitis the most severe adverse effect reported though resolving completely in 3 weeks.

Newer pharmacological agents

Newer pharmacological agents include neutrophins that act at the nerve muscle junction modulating synaptic transmission and tachykinin antagonists that mediate visceral and autonomic response to stress. Information regarding the potential benefits of these agents is limited.