Evaluation of drug treatment in irritable bowel syndrome

Abstract

The irritable bowel syndrome (IBS) remains a therapeutic challenge in part because of the limited understanding of the pathophysiology. The placebo response rate varies in randomized controlled trials from 20 to 70%, and can persist for up to at least 1 year. It is contentious whether dietary fibre and bulking agents relieve the symptoms of IBS; constipation probably improves. Anticholinergic and antispasmodic agents are of questionable benefit in IBS despite positive meta-analyses of poor quality trials. A meta-analysis concluded that the tricyclic antidepressants were superior to placebo in IBS, although the individual trial results were variable. Selective serotonin reuptake inhibitors are of uncertain benefit. Laxatives are used for constipation but probably poorly control the IBS symptom complex. Loperamide is superior to placebo in improvement of diarrhoea but not abdominal pain in IBS. Tegaserod is a well-tolerated aminoguanidine indole derivative of serotonin that is a partial 5HT 4 -receptor agonist with prokinetic properties; a therapeutic gain over placebo of 5% to 15% has been observed in constipation-predominant IBS in females. Alosetron is a 5HT 3 -receptor antagonist that is efficacious in females with diarrhoea-predominant IBS, with a 12% to 17% therapeutic gain; the risk of ischaemic colitis is 1 in 350, with very severe constipation occurring in about 1 in 1000. Optimizing study design remains a challenge in IBS. New visceral analgesic and motility modifying agents, as well as anti-inflammatory agents are in trials, and hopefully additional efficacious therapeutic options for patients with IBS will soon emerge.

Evidence-based clinical practice guidelines for irritable bowel syndrome

“…With regard to dopamine D 2 blocking agents, a smallscale RCT and meta-analysis investigated the efficacy of domperidone in IBS patients and showed the beneficial effect of this agent on gastrointestinal symptoms. No studies have yet investigated the utility of metoclopramide and its extrapyramidal side effects have been recognized [108,109]. Furthermore, no clinical evidence on the efficacy of neostigmine [110] or itopride in IBS patients is available.…”

Review article: modulation of the brain–gut axis as a therapeutic approach in gastrointestinal disease

“…The fact that drugs acting at the brain-gut axis make up an important aspect of every recent review published on the pharmacologic treatment of IBS indicates the firm support of the field for this treatment approach. 4,5,[8][9][10][11][12][13][14] Afferent signals arising from the lumen of the gut are transmitted via various visceral afferent pathways (enteric, spinal and vagal) to the CNS. 15 physiological as well as pathological visceral stimuli, occur at the level of the ENS, the spinal cord and the pontomedullary nuclei and limbic regions.…”

Effects of Itopride Hydrochloride on Plasma Gut-Regulatory Peptide and Stress-Related Hormone Levels in Healthy Human Subjects

“…On the other hand, some FD or IBS patients do not meet the diagnostic criterion of depression. These are usually treated with histamine H 2 receptor antagonists and serotonin 5-HT 4 receptor agonists [36,37] . Itopride is expected to provide equal or more effective actions, from the viewpoint of gastrointestinal peptide changes.…”