Este documento trata sobre el Síndrome de Intestino Irritable (SII). Define el SII y discute su epidemiología, fisiopatología, criterios diagnósticos, diagnósticos diferenciales y manejo. Aborda temas como la prevalencia del SII en diferentes regiones del mundo, los factores que contribuyen a su desarrollo, las comorbilidades psiquiátricas asociadas, y las opciones de tratamiento farmacológico y no farmacológico según los síntomas predominantes.
2. TEMAS A TRATAR
• Definición
• Epidemiología
• Fisiopatología
• Criterios diagnósticos
• Diagnósticos diferenciales
• Manejo
3. DEFINICIÓN
Trastornos digestivos funcionales: “Combinación variable de
síntomas gastrointestinales crónicos o recurrentes, dependientes
de la edad, que no pueden ser explicados por alteraciones
estructurales o bioquímicas”
Criterios Roma I, 1989
5. Camillieri et al. Al Pharmacol Ther, 1997
Muller – Lisner et al. Digestion 2001
Gentileza Dra. Ana María Madrid.
13%
10 – 20 %
18%
30 %
22 %
25 %
12 %
17 %
23 %
Santiago: 29%
Mapuches Carahue: 24%
Estudiantes de medicina: 26%
Región
Geográfi
ca
Nº
estudi
os
Prevalenc
ia %
Europa
del norte
21 12.0
Sudeste
asiático
19 7.0
América del
Norte
10 11.8
Europa del
Sur
9 15.0
Medioriente 8 7.5
Asia del sur 4 17.0
Sudaméric
a
4 21.0
Australia 3 14.0
Africa 2 19.0
EPIDEMIOLOGÍA SII EN EL MUNDO
6. EPIDEMIOLOGÍA
• Se estima que es entre el 25-50% de las
consultas al gastroenterólogo
• Sólo el 15% busca ayuda médica
• Es la segunda causa de mayor ausentismo
laboral después del resfrío
• Prevalencia por género:
• Mujeres: 14 % (> dolor y constipación)
• Hombres: 8.9 % (> diarrea)
• Prevalencia disminuye con la edad
Up to Date. Última actualización en octubre del 2014.
11. COMORBILIDAD PSIQUIÁTRICA
Cerca del 50% de los pacientes con SII, especialmente
aquellos de centros terciarios, tienen algún síntoma o
trastorno psiquiátrico
Surdea-Blaga T. World J Gastroenterol 2012; 18(7): 616-626
12. Mayores niveles de
ansiedad que controles
(moderada asociación)
en un reciente meta-
análisis
Henningsen et al. Psychosom Med
2003; 65:528-33
Ansiedad
Rasgos de personalidad Procesos cognitivos
y conductuales
SII
-Comportamiento de
enfermedad. Whitehead et al. Dig Dis
Sci 1982;27:2002-2008
-Hipervigilancia de síntomas.
Mayer et al. Am J Med 1999;107:15-45
-Interpretación de la causa de
los síntomas. Van der Horst et al. Gut
1997;41:669-674
-Mayor estrés por sucesos
vitales
-Más sucesos vitales
estresantes. Bennet et al. Gut
1997;42:414-420
-Estilos de afrontamiento
menos eficaces. Drossman et al.
Psychom Med 2000;62:309-317
Mayor grado de
neuroticismo
Talley et al. Gut 1998; 42:47-53
Extraído de Clase Trastornos funcionales GI 2012. Dra. Ana María Madrid. Facultad de Medicina,
Universidad de Chile. Gentileza Dra. Ana María Madrid.
COMORBILIDAD PSIQUIÁTRICA
13. Criterios Diagnósticos:
Criterios Roma III para SII
Longstreth GF, Grant WT, Chey WD, Houghton L, Mearin F, Spiller RC. Functional Bowel Disorders.
Gastroenterology 2006 Vol 130 (5): 1480-1491
• Recurrente al menos 3 días/mes
• Criterios de enfermedad en los últimos 3 meses con inicio de los síntomas
al menos 6 meses antes del diagnóstico
Malestar y /o
disconfort
abdominal
Mejoría con la
defecación
Asociado a
cambio en la
frecuencia
Asociado a
cambio en la
consistencia
14. 0
25
50
75
0 25 50 75 100
% Deposiciones sueltas o acuosas
SII-ind
SII-C
SII-M
SII-D
Roma III Subtipos de SII
100
%Deposicionesduras
%
Extraído de Clase Síndrome de Intestino Irritable
2012. Dra. Ana María Madrid. Facultad de Medicina,
Universidad de Chile. Gentileza Dra. Ana María
Madrid.
16. DIAGNÓSTICO
Adaptado de: Chey WD, Kurlander J, Eswaran S. Irritable Bowel Syndrome, A Clinical Review. JAMA 2015
Vol 313 (9): 949-958
Características Típicas
de SII
Deposiciones blandas/frecuentes
Constipación
Hinchazón
Cólicos abdominales, molestias o dolor
Síntomas desencadenados por
alimentos o sensibilidad específica
Síntomas dinámicos en el tiempo
(Cambia localización del dolor, etc)
Características de
enfermedad orgánica
Síntomas se presentan sobre los 50
años
Síntomas severos o empeoramiento
progresivo
Pérdida de peso inexplicable
Diarrea nocturna
Historia familiar de enf
gastroenterológica
Sangrado rectal o melena
Anemia ferropénica inexplicable
17. DIAGNÓSTICOS
DIFERENCIALES
Enfermedad
Celiaca
• 4 veces más
común en SII
• Se recomienda
screening en
prevalencia > 1%
(Chile 0.6-0.75%)
• Mantener bajo
umbral de
sospecha en SII-D
• Solicitar Ac ATG +
niveles IgA
Colitis
Microscópica
• Más probable
frente a
características de
enf. Orgánica.
• Si se solicita
colonoscopía,
pedirla con
biopsias
escalonada
EII
• 1/3 de los
pacientes cumplen
criterios de Roma
para SII
• <1% en pacientes
con SII sin
características de
enf. orgánica
• Biomarcadores no
invasivos:
Calciprotectina
fecal, PCR <0.5
mg/dL
Chey WD, Kurlander J, Eswaran S. Irritable Bowel Syndrome, A Clinical Review. JAMA 2015 Vol
313 (9): 949-958
ENS 2009-2010
18. DIAGNÓSTICOS
DIFERENCIALES
Malabsorción de
ácidos biliares
• 1/3 de pacientes con
síntomas de SII-D.
• Prueba empírica con
secuestrador de
ácidos biliares
Cáncer
Colorrectal
• Evidencia
contradictoria en
relación a Ca y
constipación.
• Ensayos prospectivos:
<1% en pacientes con
SII sin características
de enf. orgánica
• Recomendación:
Screening colorrectal
según edad si no hay
características de
organicidad.
Defecación
Dissinérgica
• Pacientes con SII-C
refractaria a
tratamiento: Referir a
especialista (examen
digital anal,
manometría anorectal,
test de expulsión de
balón, imagen ano-
rectal)
Chey WD, Kurlander J, Eswaran S. Irritable Bowel Syndrome, A Clinical Review. JAMA 2015 Vol
313 (9): 949-958
20. MANEJO DE PACIENTE
CON SII
Síntomas Compatibles con SII
Síntomas de Alarma
No Si
Derivar a Gastroenterologo
para colonoscopía/otros
exámenes
Enfoque
multifactorial de
tratamiento: MG
Hiperalgesia
Motilidad
Flora bacteriana
Psicosocial
Síntoma predominante: Fcos
Diarrea Dolor Estreñimiento
Normal Causa orgánica
Hemograma
22. CAMBIOS EN LA DIETA
Extraído de Clase Síndrome de Intestino Irritable 2012. Dra. Ana María Madrid. Facultad de
Medicina, Universidad de Chile. Gentileza Dra. Ana María Madrid.
23. FODMAP Fructuosa Polioles Lactosa Fructanos y Galactanos
Alto contenido de
FODMAP
(Fermentables
Oligo- Di- y
Monosacaridos y
Polioles
No
recomendables
Manzanas,
cerezas ,
peras,
sandía,
espárragos,
alcachofas,
guisantes ,
miel y jarabe
de maíz
Manzanas, damascos,
cerezas, peras, duraznos
ciruelas, sandía, palta,
coliflor, champiñones
guisantes, edulcorantes
artificiales (sorbitol,
manitol, maltitol, y xilitol)
leche ,
yogur ,
helado,
crema,
natillas, y
quesos
cremosos
(ricota y
cotage)
alcachofas , espárragos ,
remolachas,repollos
Bruselas, brócoli , coliflor,
hinojo, ajos , puerros , ají
turco, cebollas ,
legumbres, trigo, centeno
, cebada , manzanas ,
melocotones, caqui, sandía
y los pistachos.
Alternativa con
bajo contenido
Recomendable
Naranja,
mandarina
limón, berries
(frutillas,
arandales,
frambuesa)
melón, kiwi,
mangos
edulcorantes, como el
azúcar, la glucosa, otros
edulcorantes artificiales
que no terminen en ol
(sucralosa, aspartame)
productos
lácteos libres
de lactosa,
como leche
de arroz,
quesos
duros
Almidones, como el arroz,
el maíz, papa, quinoa.
Vegetales: tales como la
zapallos, lechuga,
espinacas, pepinos,
pimientos, porotos verdes,
tomate, berenjena
Extraído de Clase Síndrome de Intestino Irritable 2012. Dra. Ana Maria Madrid. Facultad de Medicina,
Universidad de Chile. Gentileza Dra. Ana María Madrid.
CAMBIOS EN LA DIETA
24. TRATAMIENTO
FARMACOLÓGICO SII-D
• Loperamida (4-12 mg/día)
• Dismininuye frecuencia de deposiciones y aumenta su consistenciaAntidiarreicos
• Alosteron y Ondansetron (4-8 mg 1-3/día)
• Mejora consistencia deposiciones, síntomas generales, urgencia,
frecuencia deposiciones e hinchazón PERO NO EL DOLOR.
Antagonistas 5HT3
• Anticolinérgicos (Trimebutina) y bloq CC (Otilonio)
• Relajan musculatura intestinal. Dolor abd y sintomas grales.
• Otilonio: Colicos abd postprandiales y deposiciones blandas.
Antiespasmódicos
• Posee bloq CC
• 187-225 mg 3/día beneficiaría a algunos pacientes.
Aceite menta
piperita
Chey WD, Kurlander J, Eswaran S. Irritable Bowel Syndrome, A Clinical Review. JAMA 2015 Vol 313 (9): 949-958
Loperamida 2mg disponible en CESFAM
Ondansentron 8mg (15 comp) = 35000 cp
Alosteron no disponible en Chile
Trimebutina 300mg (15 comp) = 500 cp
Otilonio 40mg (30 comp)
Aceite menta piperita (100ml) = 5000 cp
Mebeverina 200mg = cp
(Cuando síntoma ppal
es dolor)
25. TRATAMIENTO
FARMACOLÓGICO SII-C
• Fibra soluble: Psyllum y cáscara de ispaghula
• Beneficios modestos en sintomas globales
• Iniciar con dosis baja (5g) y titular gradualmente hasta 20-
30 g.
Suplementos
con fibra
• Laxantes osmóticos: PEG iniciar 17 g en jugo o agua.
• Mejora frecuencia de deposiciones y consistencia pero no
dolor o hinchazón. Pueden empeorar estos síntomas.
• Sin estudios controlados randomizados para SII-C
Agentes
laxantes
• Lubiprostone 8-24 ug 2/día y Linaclotide 290 ug/d
• Mejora global, disminución dolor abdominal e hinchazón.
• RAMs: Nauses. Diarrea.
Agentes
prosecretores
Chey WD, Kurlander J, Eswaran S. Irritable Bowel Syndrome, A Clinical Review. JAMA 2015 Vol 313 (9): 949-958
No disponibles en Chile
Fibrasol 100 g
Mebeverina 200mg = cp
26. OTRAS
INTERVENCIONES
Modificación de la microbiota:
• Probióticos: Mejoran dolor abdominal, hinchazón y flatulencia. Diferentes
preparaciones. No existe una recomendación específica. 2 probióticos tienen
mejor resultado que uno solo.
• Rifaximina: Mejora de síntomas generales e hinchazón en pacientes no
constipados. Dosis 550 mg 3/d x 14 d
Chey WD, Kurlander J, Eswaran S. Irritable Bowel Syndrome, A Clinical Review. JAMA 2015 Vol 313 (9): 949-958
Medicinas complementarias
• Escasez de estudios que las respalden
Intervenciones a nivel central:
• Antidepresivos: Efectivos para dolor abdominal en SII mod. A severo.
• ATC preferidos en SII-D, insomnio, anorexia o perdida de peso
• IRSS preferidos en SII-C, ansiedad.
Psicoterapia:
• Importancia de acceso y adherencia.
27. PROBIÓTICOS
Cáceres P, Gotteland M.
Alimentos Probióticos en
Chile: ¿Qué cepas y qué
propiedades
saludables?. Rev. chil.
nutr. Santiago, 2010,
37(1):97-109
28. PROBIÓTICOS
Cáceres P, Gotteland M. Alimentos Probióticos en Chile: ¿Qué cepas y qué propiedades saludables?. Rev.
chil. nutr. Santiago, 2010, 37(1):97-109
29. Chey WD, Kurlander J, Eswaran S. Irritable Bowel Syndrome, A Clinical Review. JAMA 2015 Vol 313 (9): 949-958
30. MANEJO DE PACIENTE
CON SII
Enfoque
multidisciplinario
Manejo del dolor
Antidepresivos
MEDIDAS GENERALES:
Educación, Actividad Física y
Modificación de la dieta FODMAP
+
+
Farmacoterapia
Antiespasmódicos
Antibióticos
Probioticos
Tratamiento sicológico
Síntomas infrecuentes y de baja
intensidad. Buena calidad de vida.
No busca atención médica
Mayor disconfort y persistencia
de síntomas. Afecta algunos
aspectos de la calidad de vida.
Consultan.
Síntomas más frec, más
persistentes y más
intensos. Marcado
compromiso de calidad
de vida, comorbilidades
psicosociales.
Los terminos de trastornos digestivos funcionales han sido descritos desde hace ya más de 200 años, cuando se hablaba del poder de digestion del intestino y los síntomas que este podía producir. Se empezarón a acuñar términos como colon espástico, colon irritable, síndrome de colon irritable y SII ya en 1966, pero a pesar de que ya se acuñaba el término estas molestias no estaban bien definidas. En los años 80 se comienza a sistematizar estas molestias GI en síndromes, concluyendo en un consenso en 1989 con los criterios de roma I publicados en la revista gastroenterology international, donde se plantean 25 patologías en total dejando el estima de que sólo existía el SII y la dispepcia funcional. El problema con estos criterios fue que eran demasiado estrictos por lo que realizar un diagnóstico positivo era más bien difícil y realizado a nivel de especialista. Esta problemática se intento de evitar con los criterios de roma sucesivos en 1999 y el último publicado el 2006 donde también se incluyen dg en pediatría
Los diagnósticos pueden variar de un trastorno a otro a lo largo del tiempo
Mecanismos fisiopatológicos posiblemente comunes
La fisiopatología del trastorno aún es incierta, no se ha encontrado una causa específica que se relacione con el trastorno, sino más bien hay un conjunto de procesos que explicarian, en su conjunto, la enfermedad.
El enfoque tradicional de la fisiopatología se ha relacionado con la perpeción altearada del dolor y la motilidad GI.
-Percepción alterada del dolor: hay un aumento de la sensibilidad colónica que no se sabe muy bien si es por una alteracion del SNE o del SNC
-Motilidad GI: hay una motilidad aberrante en el tracto GI, afectado la frecuencia e intensidad de las ondas lentas y el complejo motor migratorio dependiendo del predominio sindromático, que se cree que se deberia una hipersensiblidad del músculo liso GI
Sin embrag, hoy se sabe que existen otros procesos involucrados en la fisiopatología del proceso, como lo son los factores de inflamación, disbiosis (alteración de la microflora GI), y el sobrecreciemiento bacteriano, todos procesos que estan involucrados con el eje microbiota-sne-snc
Existe un cambio en la microbiota GI (hay una mor diversidad), ya sea por una infección, uso de antibióticos, stress –y con ello una activación del sistema inmune GI y aumento de la permebailidad-. La alteracion de la microbiota GI afecta el sistema inmune GI y el sistema nervioso entérico. Esto se transmite al SNC, activando el eje hipotalamo-hipofisis-gl suprarrenal. Se libera cortisol, que a su vez estable feedback negativo sobre la hipofisis, hipotalamo, pero tambien la amigadala, el hipocampo y la corteza prefrontal para que apaguen el eje HHA.
Escala de heces de bristol para evaluar la dureza de las deposiciones. En chile la prevalencia es mayor para el subtipo constipado, luego mixto y luego subtipo diarrea (al igual que en europa), a diferencia de USA donde no hay una predomino de prevalencia en los distintos subtipos
It is important to consider all prescription and over-the-counter medications and supplements that could affect IBS symptoms.
La evidencia sugiere que un diagnóstico de SII se puede realizar con confianza en para los pacientes que cumplan los criterios basados en síntomas y no tienen características de referencia debido a que el rendimiento de extensas pruebas de diagnóstico es baja. No obstante, la mayoría de los profesionales de la salud consideran SII como un diagnóstico de exclusión y se sienten incómodos confiar únicamente en los síntomas para diagnosticar que
Enf celiaca: Un meta-análisis de 5 estudios encontró un 4 veces mayor probabilidad de enfermedad celíaca demostrada por biopsia en pacientes con síntomas de SII. El análisis de decisiones sugiere que el cribado de rutina para la enfermedad celíaca en pacientes con SII se convierte en rentable con una prevalencia del mayor o igual a 1%. Dadas las posibles consecuencias a largo plazo de la falta enfermedad celíaca, los médicos que atienden a pacientes con SII debe tener un bajo umbral para la detección de ella, sobre todo en personas con SII-D
Recent literature has identified that a small subset of patients with suspected IBS-D have microscopic colitis. A recent case control study found that age older than 50 years, nocturnal stools, weight loss, shorter duration of diarrhea, recent introduction of new drugs, and comorbid autoimmune diseases were associated with an increased risk of microscopic colitis. When colonoscopy is performed in patients with suspected IBS-D, random colon biopsies should be performed to rule out microscopic colitis.
Inflammatory bowel diseases: Even low grade inflammation could alter permeability and sensitize visceral afferent neurons, leading to alterations in motility and visceral sensation. Studies suggest that more than a third of patients with inflammatory bowel disease fulfill the Rome criteria for IBS. A prospective US study that included more than 900 non constipated IBS patients and healthy controls undergoing colonoscopy found inflammatory bowel disease in less than 1% of IBS patients and none of the controls. These data argue against routine colonoscopy in patients with typical IBS symptoms and no concerning features. Noninvasive biomarkers may provide a more cost effective means by which to screen for inflammatory bowel disease than colonoscopy. A recent systematic review and metaanalysis suggested that fecal calprotectin, a biochemical assay for intestinal inflammation, was effective and cost-effective in identifying inflammatory bowel disease. Another systematic review and meta-analysis found that a C-reactive protein level of less than 0.5 mg/dL or fecal calprotectin level of less than 40 μg/g conferred a less than 1% risk of inflammatory bowel disease in patients with typical IBS symptoms.
Evidence of bile acid malabsorption may be present in up to a third of patients with IBS-D symptoms. At present, clinicians can assess for bile acid malabsorption by instituting an empirical trial with a bile acid sequestrant. Several tests have been developed to identify such malabsorption, including the SeHCAT (tauroselcholic [selenium 75] acid) retention test, serum C4 measurement, and fecal bile acid measurement. However, these tests are not widely available in the United States. It is hoped that eventually bile acid malabsorption testing will identify IBS-D patients more likely to benefit from a bile acid sequestrant.
Colorectal cancer: A meta-analysis that included cross-sectional surveys found that constipation was actually associated with a lower prevalence of colorectal cancer (odds ratio,0.56;95%CI,0.36 0.89). This analysis also found no significant increase in colorectal cancer risk among constipated patients vs non constipated controls in 3 cohort studies (odds ratio,0.80;95%CI,0.61-1.04). However, a more recent case control study found that patients with chronic constipation have a significantly higher prevalence and incidence of colorectal cancer and benign colorectal neoplasms. The limited prospective literature suggests that the risk of colorectal cancer is less than 1% in patient with typical IBS symptoms and no concerning features and not increased compared with that in healthy controls. As such, in patients with typical IBS symptoms and no concerning features, age appropriate colorectal cancer screening is the most logical recommendation.
Dyssynergic defecation: A constipation-associated condition that arises from the inability to coordinate the abdominal wall, anal sphincter, and pelvic floor muscles in a way that enables normal defecation. Although a sense of incomplete evacuation after a bowel movement or the need for digital maneuvers to facilitate defecation may increase the likelihood of dyssynergia, symptoms generally do not accurately identify affected patients. Dyssynergia can cause abdominal symptoms such as pain, discomfort, and bloating, which are relevant to IBS-C. Preliminary data suggest that correction of dyssynergia with biofeedback can improve both bowel and abdominal symptoms. Thus, patients with medically refractory IBS-C symptoms should be referred to a specialist for evaluation of dyssynergia with a digital rectal examination, anorectal manometry, balloon expulsion testing, or anorectal imaging.
Physically active individuals move their bowels more often and have more rapid colon transit than sedentary individuals. A simple recommendation is to take a 20-minute walk (roughly 1 mile) each day. Distance and pace can be gradually increased as tolerated.
Up to 90% of IBS patients restrict their diet to prevent or improve their symptoms. At present, there is emerging evidence that supports diets for IBS patients that are gluten free and low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP). The effect of gluten was assessed by a randomized, double blind, placebo-controlled, rechallenge trial in 34 IBS patients with a history of gluten sensitivity. Gluten worsened pain, bloating, and stool consistency, as well as “tiredness.”. It is also likely that widespread negative media reports about gluten have increased the chance of a “nocebo” response, contributing to the perceived negative effects of eating gluten containing foods.
Short-chain, poorly absorbed, highly fermentable carbohydrates are collectively known as FODMAPs and are found in such foods as wheat, onions, some fruits and vegetables, sorbitol, and some dairy. FODMAPs lead to increased small intestinal and colonic water secretion and fermentation, which causes increased production of short-chain fatty acids and gas. Aside from increased flatulence, FODMAPs do not cause gastrointestinal symptoms in healthy adults. Conversely, FODMAPs are an important trigger of meal-related symptoms in IBS patients, possibly as a consequence of underlying abnormalities in gut physiology and visceral sensation. Responders to full FODMAP exclusion should gradually reintroduce FODMAP containing foods to identify the level of dietary restriction needed to maintain symptom benefit. There are currently few long-term efficacy or safety data for the low-FODMAP diet.
Antidiarrheals like loperamide inhibit peristalsis, prolong gut transit, reduce fecal volume, and are often used as first-line agents in patients with IBS-D. Two randomized trials enrolling IBS-D and IBS-M patients found no benefit of loperamide over placebo for overall IBS symptoms. However, loperamide reduces stool frequency, increases stool consistency, and can be used prophylactically when a patient anticipates diarrhea.
Serotonin Agents: 5-HT3 Receptor Antagonists. The gut hormone serotonin influences gastrointestinal motility and visceral sensation. Alosetron is a 5-HT antagonist approved in the United States for treating women with severe, disabling IBS-D that has not responded to traditional medical therapies. Ondansetron, a 5-HT3 antagonist that is less potent than alosetron, has been shown to benefit IBS-D in a recent randomized, double-blind, placebo-controlled, crossover study. Ondansetron (4-8 mg 1-3 times per day) significantly improved stool consistency, global IBS symptoms, urgency, stool frequency, and bloating but not pain.
Antispasmodics include drugs with anticholinergic (ej:trimebutina) or calcium channel blocking (ej: otilonio) properties that may improve IBS symptoms by relaxing gut smooth muscle. A 2011 Cochrane review reported benefits of antispasmodics over placebo for abdominal pain and global assessment. The American College of Gastroenterology Functional Bowel Disorders Task Force recently concluded that “certain antispasmodics (otilonium, hyoscine, cimetropium, pinaverium, and dicyclomine) provide symptomatic short-term relief in IBS.” Because some IBS patients have an exaggerated gastrocolonic reflex that is in part cholinergically mediated,these drugs may be best suited for postprandial abdominal cramping and loose stools. Dose-dependent adverse events, including constipation, fatigue, dry mouth, dizziness, and blurred vision, may occur. Anticholinergics should be avoided in the elderly.
Peppermint oil, which is available over the counter, possesses calcium-channel blocking properties and thus is classified as an antispasmodic.A number of small clinical trials suggest that enteric peppermint oil (187-225 mg 3 times daily) benefits some IBS patients. Although peppermint oil is typically well tolerated, some patients may experience reflux symptoms.
Fiber Supplements: The most recent meta-analysis reported modest benefits with fiber for global IBS symptoms (relative risk, 0.86; 95% CI, 0.80-0.94; number needed to treat, 10). In a subgroup analysis, soluble fiber (psyllium and ispaghula husk; relative risk, 0.84; 95% CI, 0.73-0.94) but not insoluble fiber (wheat bran) was associated with improved IBS symptoms. Fiber, which is often usedas a first-line therapy, should be started at a nominal dose and gradually titrated upward during weeks to a total daily intake of 20 to 30 g.
Laxative Agents: Osmotic laxatives such as polyethylene glycol are frequently recommended as first-line therapy for IBS-C patients. Clinical trials have demonstrated that it improves bowel complaints, includings tool frequency and consistency, but does not reliably improve abdominal pain or bloating. The usual starting dose is 17 g in juice or water, with dose escalation dictated by clinical response. Polyethylene glycol is typically well tolerated but can cause dose-dependent bloating, gas, and loose stools. Stimulant laxatives are also commonly used in IBS-C patients. Although efficacy has been demonstrated in patients with chronic constipation, to our knowledge there are no randomized, controlled trials in IBS-C patients. Relevant to IBS, the most common adverse effects are abdominal pain and cramping.
Prosecretory Agents: Luminally acting prosecretory agents have been evaluated in IBS-C patients. Lubiprostone is a chloride-channel (ClC-2) activator that stimulates intestinal fluid secretion and improves global, bowel, and abdominal symptoms in IBS-C patients. In phase trials(1711IBS-C patients), a significantly higher percentage of patients treated with lubiprostone 8 μg twice daily responded compared with those treated with placebo (17.9% vs 10.1%; P = .001). A higher dosage of 24 μg has proven effective in patients with chronic idiopathic constipation. To limit dose-dependent nausea (8% with an 8-μg dose and 33% with a 24-μg dose), lubiprostone should be received with food. Linaclotide is a guanylate cyclase-C agonist that increases production of cyclic guanosine monophosphate. Intracellularly, cyclic guanosine monophosphate increases intestinal chloride secretion via the cystic fibrosis transmembrane regulator, whereas extracellularly it reduces firing of visceral afferent pain fibers. A 2013 meta-analysis that included 3 rigorous randomized clinical trials in IBS-C patients reported a relative risk for response to linaclotide (290 μg once daily) vs placebo of 1.95 (95% CI, 1.3-2.9) and a number needed to treat of 7 (95% CI, 5-11).80 The maximum benefit for stool frequency occurs within a week of treatment initiation, whereas abdominal pain and bloating may take 8 to 12 weeks to maximally improve.
Modification of the Microbiota: The most robust data have evaluated the role of probiotics for IBS. Rifaximin is a poorly absorbed, broad-spectrum antibiotic that has been evaluated in IBS patients. A recent meta-analysis that included 5 randomized clinical trials that enrolled predominantly non constipated IBS patients demonstrated therapeutic gains of 9% to 10% for global symptoms (odds ratio, 1.57; 95% CI, 1.22-2.01) and bloating (odds ratio, 1.55; 95% CI, 1.23-1.96).The 2 phase 3 trials in non constipated IBS patients used rifaximin 550 mg 3 times daily for 14 days. Clinical experience suggests that many rifaximin responders will eventually develop recurrent IBS symptoms. Recently released data from a large re-treatment trial suggest that second and third courses yield efficacy similar to that of the first course of rifaximin.
Centrally Acting Interventions. Antidepressants: Because of their effects on pain perception, mood, and motility, antidepressants have become a widespread treatment option for patients with moderate to severe IBS. The efficacy of tricyclic antidepressants, selective serotonin-reuptake inhibitors, and, to a lesser extent, selective norepinephrine reuptake inhibitors has been evaluated in IBS patients. Collectively, antidepressants were effective for abdominal pain, with a relative risk of remaining symptomatic of 0.62 (95% CI, 0.43-0.88) and a number needed to treat of 4 (95% CI, 3-6). A subgroup analysis reported a number needed to treat of 4 for both tricyclic antidepressants and selective serotonin reuptake inhibitors. Adverse events occurred more often in patients receiving an antidepressant (number needed to harm, 9; 95% CI, 5-111). Tricyclic antidepressants can cause dose-dependent constipation, dry mouth and eyes, drowsiness, weight gain, and QTinterval prolongation. Selective serotonin-reuptake inhibitors can cause sexual dysfunction, agitation, nausea, drowsiness, and diarrhea. Although selective norepinephrine-reuptake inhibitors offer benefits for anxiety, depression, and somatic pain,there are few data addressing their efficacy for IBS. The adverse event profiles of different antidepressants can be leveraged to address different IBS subtypes. For example, because tricyclic antidepressants can cause constipation, they may be best suited to IBS-D patients, whereas the prokinetic effects of selective serotonin-reuptake inhibitors might make them a better choice for IBS-C patients. Similarly, tricyclic antidepressants might be a better choice for patients with insomnia, anorexia, or weight loss.On the other hand,selective serotonin-reuptake inhibitors might be a better choice for patients with significant anxiety. When a tricyclic antidepressant is selected to treat IBS, low doses (10-25 mg) should be started at bedtime and gradually titrated upward according to symptom response and tolerability. Selective serotoninreuptake inhibitors are typically started at the lower range of standard dosing
Psychological Therapies: provide an alternative or adjunctive therapy for IBS patients. In a recent meta-analysis, 32 separate trials of highly variable quality, involving more than 2000 patients, evaluated 10 different “psychological therapies,” which were more effective than control therapies, with a number needed to treat of 4 (95% CI, 3-5). In a subgroup analysis, similar numbers needed to treat were reported for cognitive behavioral therapy, hypnotherapy, multicomponent psychotherapy, and dynamic psychotherapy but not other techniques. Despite these encouraging results, variable third party reimbursement, a lack of clinicians, and poor patient and clinician acceptance have limited widespread adoption of these therapies in clinical practice. Access to behavioral therapy may improve with the development of book-, Internet-, or application-based behavioral programs.
In When IBS is “severe,” the symptoms are more frequent, even persistent, and of greater intensity, and associ- ated with marked function impairment, psychosocial comorbidi- ties, and health-care referrals to specialists