Irritable bowel syndrome and functional constipation management with integrative medicine: A systematic review

Table 1 General information of 30 clinical practice guidelines

Disease	No.	Title	Publication year	Academic organization	Category	Medical system
Irritable bowel syndrome	1	American Gastroenterological Association medical position statement: Irritable bowel syndrome	2002	American Gastroenterological Association (AGA)	EB	WM
	2	Guidelines on the irritable bowel syndrome: mechanisms and practical management	2007	British Society of Gastroenterology (BSG)	EB	WM
	3	Asian consensus on irritable bowel syndrome	2010	Asian Neurogastroenterology and Motility Association (ANMA)	EB	WM
	4	Diagnosis and treatment consensus on irritable bowel syndrome with traditional Chinese medicine	2010	China Society of Digestive Diseases in Chinese Medicine	CB	TCM
	5	Irritable bowel syndrome--the main recommendations	2011	German Society for Digestive and Metabolic Diseases (DGVS) German Society for Neurogastroenterology and Motility (DGNM)	EB	WM
	6	Consensus on irritable bowel syndrome by integrative medicine	2011	Speciality Committee of Digestive Diseases, Chinese Association of Integrative Medicine (CAIM)	CB-EB	IM
	7	American Gastroenterological Association Institute Guideline on the pharmacological management of irritable bowel syndrome	2014	American Gastroenterological Association (AGA)	EB	WM
	8	Evidence-based clinical practice guidelines for irritable bowel syndrome	2015	Japanese Society of Gastroenterology (JSGE)	EB	WM
	9	Irritable bowel syndrome: a global perspective	2015	World Gastroenterology Organisation (WGO)	CB-EB	WM
	10	Irritable bowel syndrome in adults: diagnosis and management	2015	National Collaborating Centre for Nursing and Supportive Care (NICE)	CB-EB	WM
	11	Expert consensus on irritable bowel syndrome in China	2016	Chinese Society of Gastroenterology (CSGE)	EB	WM
	12	Danish national guideline: Diagnosis and treatment of irritable bowel syndrome	2017	Danish Society for Gastroenterology and Hepatology (DSGH)	EB	WM
	13	Diagnosis and treatment consensus on irritable bowel syndrome with traditional Chinese medicine (2017)	2017	China Society of Digestive Diseases in Chinese Medicine	CB	TCM
	14	The current treatment landscape of irritable bowel syndrome in adults in Hong Kong: Consensus statements	2017	Multidisciplinary group of clinicians	CB-EB	WM
	15	Diagnosis and treatment consensus on irritable bowel syndrome with integrative medicine (2017)	2017	Speciality Committee of Digestive Diseases, Chinese Association of Integrative Medicine (CAIM)	CB	IM
	16	Clinical practice guidelines for irritable bowel syndrome in Korea, 2017 revised edition	2018	Korean Society of Neurogastroenterology and Motility (KSNM)	EB	WM
Functional constipation	1	Diagnosis and treatment consensus on functional constipation with traditional Chinese medicine	2011	China Society of Digestive Diseases in Chinese Medicine	CB	TCM
	2	World Gastroenterology Organisation global guideline constipation - a global perspective	2011	World Gastroenterology Organisation (WGO)	CB-EB	WM
	3	Consensus statement AIGO/SICCR: Diagnosis and treatment of chronic constipation and obstructed defecation	2012	Italian Association of Hospital Gastroenterologists (AIGO), Italian Society of Colo-Rectal Surgery (SICCR)	EB	WM
	4	American Gastroenterological Association medical position statement on constipation	2013	American Gastroenterological Association medical (AGA)	EB	WM
	5	Diagnosis and treatment guideline of chronic constipation in China	2013	Gastrointestinal Motility Group of Digestive Disease Branch and Colorecatal Group of Surgery Branch of Chinese Medical Association	CB-EB	WM
	6	Guideline for the diagnosis and treatment of chronic functional constipation in Korea, 2015 revised edition	2016	Korean Society of Neurogastroenterology and Motility (KSNM)	EB	WM
	7	Diagnosis and treatment expert consensus on chronic constipation with traditional Chinese medicine (2017)	2017	China Association of Chinese Medicine (CACM)	CB	TCM
	8	Diagnosis and treatment consensus on chronic constipation with integrative medicine	2018	Chinese Association of Integrative Medicine (CAIM)	CB	IM
	9	Clinical practice guidelines from the French National Society of Coloproctology in treating chronic constipation	2018	French National Society of Coloproctology (SNFCP)	EB	WM
	10	Indian consensus on chronic constipation in adults: A joint position statement of the Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology	2018	Indian Motility and Functional Diseases Association, Indian Society of Gastroenterology	EB	WM
Both	1	Recommendations on chronic constipation (including constipation associated with irritable bowel syndrome) treatment	2007	Canadian Association of Gastroenterology (CAG)	EB	WM
	2	Guidelines for diagnosis and treatment of common internal diseases in Chinese medicine: Diseases of modern medicine	2008	China Association of Chinese Medicine (CACM)	CB	TCM
	3	American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation	2014	American College of Gastroenterology (ACG)	EB	WM
	4	Clinical practice guideline: Irritable bowel syndrome with constipation and functional constipation in the adult	2016	Sociedad Española de Patología Digestiva (SEPD), Sociedad Española de Medicina de Familia y Comunitaria (semFYC), Sociedad Española de Médicos de Atención Primaria (SEMERGEN) and Sociedad Española de Médicos Generales y de Familia (SEMG)	EB	WM

CB: Consensus-based; CB-EB: Consensus-based with no comprehensive consideration of evidence-based; EB: Evidence-based; IM: Integrative medicine; TCM: Traditional Chinese medicine; WM: Western medicine.

Table 2 Strengths of recommendations regarding pharmacological interventions for irritable bowel syndrome in 20 clinical practice guidelines

	Drugs	Recommendations by CPGs
Pain	Antispasmodics	Strongly recommended or recommended by 13 CPGs; weak evidence reported by 1 CPG
	Peppermint oil	Strongly recommended or recommended by 4 CPGs
	TCAs1	Strongly recommended or recommended by 10 CPGs; weak evidence reported by 3 CPG
	SSRIs	Strongly recommended or recommended by 10 CPGs; weak evidence reported by 3 CPG
Diarrhea	Loperamide	Recommended by 9 CPGs; weak evidence reported by 3 CPG
	Alosetron2	Strongly recommended or recommended by 7 CPGs
	Eluxadoline	Strongly recommended by 1 CPG; insufficient evidence reported by 1 CPG
Constipation	Mosapride	Recommended by 1 CPG
	Prucalopride	Insufficient evidence reported by 5 CPGs
	PEG	Recommended by 6 CPGs; weak evidence reported by 1 CPG; insufficient evidence reported by 7 CPGs3
	Linaclotide	Strongly recommended or recommended by 7 CPGs
	Lubiprostone	Strongly recommended by 6 CPGs; insufficient evidence reported by 1 CPG
Global symptoms	Probiotics	Strongly recommended or recommended by 6 CPGs; weak or insufficient evidence reported by 5 CPG
	Rifaximin	Recommended by 6 CPGs; weak or insufficient evidence reported by 5 CPG

¹TCAs should be avoided in irritable bowel syndrome-C patients;

²Alosetron should only be used in women with severe irritable bowel syndrome-D;

³PEG was considered to have insufficient evidence regarding global symptom improvement.

TCAs: Tricyclic antidepressants; PEG: Polyethylene glycol; CPG: Clinical practice guidelines.

Table 3 Strengths of recommendations regarding pharmacological interventions for functional constipation in 14 clinical practice guidelines

Category	Drugs	Recommendations by CPGs
Bulking agents	Psyllium	Strongly recommended or recommended by 10 CPGs
	Bran	Recommended by 2 CPGs, insufficient evidence reported by 6 CPGs
Stool softeners	Docusate sodium	Insufficient evidence reported by 4 CPGs
	Liquid paraffin	Insufficient evidence reported by 4 CPGs
	Glycerin	Insufficient evidence reported by 4 CPGs
Osmotic laxatives	PEG	Strongly recommended or recommended by 10 CPGs
	Lactulose	Recommended by 10 CPGs
	Magnesium salts	Recommended by 1 CPG, insufficient evidence reported by 2 CPGs
Stimulant laxatives	Bisacodyl	Recommended by 9 CPGs, weak evidence reported by 1 CPG, insufficient evidence reported by 1 CPG
	Sodium picosulfate	Recommended by 9 CPGs, weak evidence reported by 1 CPG, insufficient evidence reported by 1 CPG
	Senna	Insufficient evidence reported by 6 CPGs
Prosecretory agents	Lubiprostone	Strongly recommended or recommended by 7 CPGs
	Linaclotide	Strongly recommended or recommended by 7 CPGs
Others	Prucalopride	Strongly recommended or recommended by 9 CPGs
	Probiotics	Insufficient evidence reported by 6 CPGs
	Enema and suppositories	Weak evidence reported by 6 CPGs, Strongly recommended by 1 CPG (CO2-releasing suppositories for distal constipation)

PEG: Polyethylene glycol; CPG: Clinical practice guidelines.

Table 4 Patterns listed in three traditional Chinese medicine clinical practice guidelines and two integrative medicine clinical practice guidelines for irritable bowel syndrome

Title	IBS-D						IBS-C					IBS-M
	A	B	C	D	E	F	G	H	I	J	K	L
Guidelines for diagnosis and treatment of common internal diseases in Chinese medicine: diseases of modern medicine: irritable bowel disease
	*	*	*				*	*				*
Diagnosis and treatment consensus on irritable bowel syndrome with traditional Chinese medicine
	*	*	*	*			*		*
Consensus on irritable bowel syndrome by integrative medicine
	*				*		*		*			*
Diagnosis and treatment consensus on irritable bowel syndrome with traditional Chinese medicine (2017)
	*	*	*	*		*	*	*	*	*	*
Diagnosis and treatment consensus on irritable bowel syndrome with integrative medicine (2017)
	*		*	*	*		*		*			*

A: Pattern of liver depression and spleen deficiency: diarrhea right after abdominal pain onset, pain relieving after diarrhea, symptoms onset related to emotions, impatience and irritability, frequent sighing, distention and fullness in chest and hypochondrium, pale red tongue, thin and white fur, string-like pulse or string-like and fine pulse; B: Pattern of spleen deficiency with dampness encumbrance: abdominal pain or discomfort, sloppy stool or diarrhea, onset or exacerbation after overworking and/or cold attacking, pale and enlarged tongue or with teeth-marked, white and slimy fur, weak pulse; C: Pattern of spleen-kidney yang deficiency: diarrhea right after abdominal pain onset when getting-up, cold pain in abdomen, pain relieving after warming, cold body and limbs, soreness and weakness of waist and knees, pale and enlarged tongue, white and slimy fur, sunken and fine pulse; D: Pattern of spleen-stomach dampness-heat: diarrhea combined with abdominal pain, urgent or ungratifying diarrhea, burning pain in anus, bitter taste in the mouth, red tongue, yellow and slimy fur, slippery and rapid pulse; E: Pattern of spleen-stomach weakness: diarrhea after diet, sloppy stool or diarrhea with mucus, torpid intake, abdominal distention after diet, gastric stuffiness, pale and enlarged tongue with teeth-marked, white fur, fine and weak pulse; F: Pattern of cold-heat complex: loose stool or diarrhea at times, abdominal pain before defecation and alleviation after defecation, abdominal distension or borborygmus, bitter taste or bad breath, intolerance of cold, easily attack after cold, pale tongue, thin yellow fur, string-like and thin pulse or string-like and slippery pulse; G: Pattern of liver depression and qi stagnation: constipation, hard bound stool, difficult evacuation, abdominal pain and distention, exacerbation when emotional disorder, distention and fullness in chest and hypochondrium, frequent sighing, red tongue, thin, white or yellow, and slimy fur, string-like pulse; H: Pattern of deficiency of blood and yin: abdominal pain and discomfort, dry stool like globule, difficult evacuation, dizziness and palpitation, insomnia with dreaminess, pale complexion, lips and nails, pale red or red tongue, thin and white fur, fine and weak pulse; I: Pattern of dryness-heat of intestines: dry stool like globule with mucus outside, difficult evacuation, lump in the lower abdomen, distending pain when pressing, red tongue, yellow and dry fur, fine and rapid pulse; J: Pattern of spleen-kidney yang deficiency: dry or less dry stool, difficult defecation, cold pain in abdomen and alleviation after warm, clear and abundant urine, lack of warm in limbs, bright pale complexion, pale tongue, white fur, sunken and slow pulse; K: Pattern of lung-spleen qi deficiency: less dry and hard stool, difficult defecation but with desire, abdominal pain before defecation, tiredness and short of breath, laziness of speech, lack of strength after defecation, pale tongue, white fur, weak pulse; L: Pattern of cold-heat complex: alternative diarrhea and constipation, abdominal pain and discomfort, stuffiness and fullness in abdomen, bitter taste in the mouth, dark red tongue, thin yellow fur or white slimy fur, string-like and fine pulse or string-like and slippery pulse. IBS: Irritable bowel syndrome.

Table 5 Patterns listed in three traditional Chinese medicine clinical practice guidelines and one integrative medicine clinical practice guidelines for functional constipation

Title	FC
	A	B	C	D	E	F	G
Guidelines for diagnosis and treatment of common internal diseases in Chinese medicine: diseases of modern medicine: functional constipation	*	*	*	*	*
Diagnosis and treatment consensus on functional constipation with traditional Chinese medicine	*	*	*	*		*
Diagnosis and treatment expert consensus on chronic constipation with traditional Chinese medicine (2017)	*	*	*	*	*	*	*
Diagnosis and treatment consensus on chronic constipation with integrative medicine	*	*	*	*	*	*	*

A: Pattern of intestinal excess heat: Dry bound stool, abdominal pain and/or distention, dry and bitter taste in the mouth, scant reddish urine, reddened complexion, vexation and inability to sleep, red tongue, yellow and dry fur, slippery and rapid pulse; B: Pattern of intestinal qi stagnation: Inhibited defecation, dry or non-dry stool, abdominal pain and distention, borborigmus and frequent fecal qi, frequent belching, agitation or depression, pale red tongue, thin and slimy fur, string-like pulse; C: Pattern of dual deficiency of the lung-spleen: Difficult defecation but with desire, sweating and short of breath after exerting strength, lack of strength after defecation, lassitude of spirit and laziness of speech, pale tongue, white fur, weak pulse; D: Pattern of spleen-kidney yang deficiency: Difficult defecation, clear and abundant urine, cold pain in abdomen, lack of warm in limbs, bright pale complexion, pale tongue, white fur, sunken and slow pulse; E: Pattern of yin deficiency and intestinal dryness: Dry bound stool like globule, dry mouth and less fluid, vexation and insomnia, tidal fever and night sweating, red tongue, scanty fur, thin and rapid pulse; F: Pattern of fluid depletion and blood deficiency: Dry bound stool like globule, dry mouth and less fluid, dizziness and tinnitus, soreness and weakness of waist and knees, palpitations and fearful throbbing, pale or red tongue, white or scanty fur, weak pulse; G: Pattern of cold accumulation: Difficult defecation, urgent and cold pain in abdomen with relief by warmth, lack of warm in limbs, light and dark tongue, white and greasy fur, string-like and tight pulse. FC: Functional constipation.

Table 6 Chinese formulas listed in three traditional Chinese medicine clinical practice guidelines and two integrative medicine clinical practice guidelines for irritable bowel syndrome

	Pattern	Formula	Patent medicine
IBS-D	A	Tongxieyao formula and Sini powder	-
	B	Shenlingbaizhu powder	Shenlingbaizhu granules
	C	Fuzilizhong decoction and Sishen pills	Gubenyichang tablets, Bupiyichang pills and Sishen pills
	D	Gegengqinlian decoction	Gegengqinlian micro pills
	E	Shenlingbaizhu powder	Shenlingbaizhu granules
	F	Wumei pills	-
IBS-C	G	Sini powder, Wumo decoction and Liumo decoction	Simo decoction oral liquid and Liuweinengxiao capsules
	H	Siwu decoction and Zengye decoction	Ziyinrunchang oral liquid
	I	Maziren pills	Marenrunchang pills
	J	Jichuan decoction	Qirongrunchang oral liquid
	K	Huangqi decoction	-
IBS-M	L	Banxiaxiexin decoction Wumei pills	Wumei pills

A: Pattern of liver depression and spleen deficiency; B: Pattern of spleen deficiency with dampness encumbrance; C: Pattern of spleen-kidney yang deficiency; D: Pattern of spleen-stomach dampness-heat; E: Pattern of spleen-stomach weakness; F: Pattern of cold-heat complex; G: Pattern of liver depression and qi stagnation; H: Pattern of deficiency of blood and yin; I: Pattern of dryness-heat of intestines; J: Pattern of spleen-kidney yang deficiency; K: Pattern of lung-spleen qi deficiency; L: Pattern of cold-heat complex. IBS: Irritable bowel syndrome.

Table 7 Chinese formulas listed in three traditional Chinese medicine clinical practice guidelines and one integrative medicine clinical practice guidelines for functional constipation

Pattern	Decoction	Patent medicine
A	Maziren pills	Marenrunchang pills, Maren pills and Huanglianshangqing pills
B	Liumo decoction	Muxiangliqi tablets, Zhishidaozhi pills, Muxiangbinlang pills and Simotang oral liquid
C	Huangqi decoction	Bianmitong oral liquid and Qirongrunchang oral liquid
D	Jichuan decoction	Banliu pills and Congrongtongbian oral liquid
E	Zenye decoction	Tongle granules
F	Runchang pills	Wurenrunchang pills

A: Pattern of intestinal excess heat; B: Pattern of intestinal qi stagnation; C: Pattern of deficiency of spleen and qi; D: Pattern of spleen-kidney yang deficiency; E: Pattern of yin deficiency and intestinal dryness; F: Pattern of fluid depletion and blood deficiency.