Irritable bowel syndrome: Pathogenesis, diagnosis, treatment, and evidence-based medicine

Table 1 Summary of diagnostic criteria used to define irritable bowel syndrome

Diagnostic criteria	Symptoms, signs, and laboratory investigations included in criteria
Manning (1978)	IBS is defined as the symptoms given below with no duration of symptoms described. The number of symptoms that need to be present to diagnose IBS is not reported in the paper, but a threshold of three positive is the most commonly used:
	Abdominal pain relieved by defecation
	More frequent stools with onset of pain
	Looser stools with onset of pain
	Mucus per rectum
	Feeling of incomplete emptying
	Patient-reported visible abdominal distension
Kruis (1984)	IBS is defined by a logistic regression model that describes the probability of IBS. Symptoms need to be present for more than two years.
	Symptoms:
	Abdominal pain, flatulence, or bowel irregularity
	Description of character and severity of abdominal pain
	Alternating constipation and diarrhea
	Signs that exclude IBS (each determined by the physician):
	Abnormal physical findings and/or history pathognomonic for any diagnosis other than IBS
	Erythrocyte sedimentation rate > 20 mm/2 h
	Leukocytosis > 10000/cc
	Anemia (Hemoglobin < 12 for women or < 14 for men)
	Impression by the physician that the patient has rectal bleeding
Rome I (1990)	Abdominal pain or discomfort relieved with defecation, or associated with a change in stool frequency or consistency,
	PLUS two or more of the following on at least 25% of occasions or days for 3 mo:
	Altered stool frequency
	Altered stool form
	Altered stool passage
	Passage of mucus
	Bloating or distension
Rome II (1999)	Abdominal discomfort or pain that has two of three features for 12 wk (need not be consecutive) in the last one year:
	Relieved with defecation
	Onset associated with a change in frequency of stool
	Onset associated with a change in form of stool
Rome III (2006)	Recurrent abdominal pain or discomfort three days per month in the last 3 mo associated with two or more of:
	Improvement with defecation
	Onset associated with a change in frequency of stool
	Onset associated with a change in form of stool

IBS: Irritable bowel syndrome; 5-HT: 5-hydroxytryptamine.

Table 2 Emerging therapies for irritable bowel syndrome

Agent	Mechanism of action	Targeted disorder	Clinical status
Peripheral acting agents
Crofelemer	CFTR inhibitor	IBS-D	Phase 2b complete
Linaclotide (MD-1100)	Guanylatecyclase-c agonist	IBS-C	Approved by US FDA in 2012, 30th August
Arverapamil (AGI-003)	Calcium channel blocker	IBS-D	Phase 3
Verapamil	Kappa opioid agonist	IBS	Phase 2b complete
Mitemcinal	Motilin receptor agonist	IBS-C	Phase 2
Peripheral and central acting agents
Ramosetron	5-HT 3 antagonist	IBS-D	Phase 3
TD-5108	5-HT 4 agonist	IBS-C	Phase 2
DDP-773	5-HT 3 agonist	IBS-C	Phase 2
BMS-562086	Corticotropin-releasing hormone antagonist	IBS-D	Phase 2
GW876008	(319) Corticotropin-releasing hormone antagonist	IBS	Phase 2
DDP-225	5-HT 3 antagonist and NE reuptake inhibition	IBS-D	Phase 2
GTP-010	Glucagon-like peptide	IBS pain	Phase 2
AGN-203818	Alpha receptor agonist	IBS pain	Phase 2
Solabegron	Beta-3 receptor agonist	IBS	Phase 2
Espindolol (AGI-011)	Beta receptor antagonist	IBS (all subtypes)	Phase 2
Dextofisopam	2,3 benzodiazepine receptors	IBS-D and IBS-M	Phase 3

IBS-C: Irritable bowel syndrome with constipation; IBS-D: Irritable bowel syndrome with diarrhea; IBS-M: Mixed irritable bowel syndrome; CFTR: Cystic fibrosis transmembrane conductance regulator; US FDA: United States Food and Drug Administration.