| |
Important Note: The following information
is provided for your education. It should not be relied upon for
personal diagnosis or treatment. If you believe that a
particular therapy applies to you or someone you care about, be
sure to consult a doctor before trying it.
Irritable Bowel Research:
2002-2006
Z Gastroenterol. 2006 Aug;44(8):651-656.
[Probiotic Drug Therapy with E. coli Strain Nissle 1917 (EcN):
Results of a Prospective Study of the Records of 3807 Patients.]
[Article in German]
Krammer HJ, Kamper H, von Bunau R, Zieseniss E, Stange C, Schlieger F, Clever I,
Schulze J.
Praxis fur Gastroenterologie am Enddarmzentrum Mannheim.
INTRODUCTION: Living microorganisms that enter the gut in an active state and
exert a positive influence on the host are called probiotics. Numerous
experimental and clinical studies were performed recently and confirm both the
efficacy and modes of action of probiotic drugs. PATIENTS AND METHODS: In a
post-marketing-surveillance study with the probiotic ESCHERICHIA COLI strain
Nissle 1917 (EcN) data on the range of indications as well as on efficacy and
tolerance were gathered prospectively in 446 centres. The intended treatment
duration was limited to a maximum of 12 weeks. RESULTS: EcN was used in 3807
patients with more than 20 different indications, n = 3511 of whom had
gastrointestinal complaints: Among others, 1067 patients presented with
chronically recurring (n = 728) or protracted diarrhoea (n = 339), 415 with
inflammatory bowel disease, 679 with irritable bowel syndrome, and 253 with
chronic constipation. The overall efficacy was assessed as good to very good by
an average of 81.4 % of the therapists. The stool frequency and consistency as
well as the symptoms of meteorism and abdominal pain were improved in very many
patients. Suspected cases of side effects were documented in only 2.8 % of the
patients. CONCLUSION: EcN is frequently used in practice for the treatment of
various, mostly gastrointestinal, complaints and is well tolerated.
-----
Nippon Rinsho. 2006 Aug;64(8):1495-500.
[Treatment for irritable bowel syndrome—psychotropic drugs,
antidepressants and so on]
[Article in Japanese]
Sato M, Murakami M.
First Department of Internal Medicine, Nihon University School of Medicine.
Irritable bowel syndrome (IBS) is a functional disease with good prognosis,
which is diagnosed by exclusion of possible causative organic diseases. However,
since the patients tend to have strong psychotic symptoms including anxiety,
tension, depression, irritation and insomnia, this syndrome has to be elucidated
as a psychosomatic disease. Although the symptoms are usually limited to
gastrointestinal symptoms such as abdominal pain and abnormal bowel movements,
many patients also manifest some kinds of psychiatric abnormalities such as
hypochondria, depression, hysteria, panic disorder and posttraumatic stress
disorder. Especially, the prevalence of depression is high. Therefore, use of
psychotropic drugs is efficient in treating IBS. Antidepressant agents including
tricyclic agents such as amitriptyline, trimipramine, imipramine, clomipramine,
amoxapine and nortriptyline; tetracyclic antidepressant; antidepressants such as
SSRI and SNRI; sulpiride; benzodiazepine class anxiolytic agents; tandospirone;
and Chinese herbal medicine are being used. IBS is a stress-related disease.
Therefore, in spite of the importance of pharmacotherapy, patients should also
be instructed to avoid the stress that aggravates the symptoms in all aspects of
daily life.
-----
Am J Gastroenterol. 2006 Jul;101(7):1581-90.
Efficacy of an encapsulated probiotic Bifidobacterium infantis
35624 in women with irritable bowel syndrome.
Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O'Mahony L, Kiely B,
Shanahan F, Quigley EM.
Department of Medicine, University of Manchester, Manchester, UK.
BACKGROUND: Probiotic bacteria exhibit a variety of properties, including
immunomodulatory activity, which are unique to a particular strain. Thus, not
all species will necessarily have the same therapeutic potential in a particular
condition. We have preliminary evidence that Bifidobacterium infantis 35624 may
have utility in irritable bowel syndrome (IBS). OBJECTIVES: This study was
designed to confirm the efficacy of the probiotic bacteria B. infantis 35624 in
a large-scale, multicenter, clinical trial of women with IBS. A second objective
of the study was to determine the optimal dosage of probiotic for administration
in an encapsulated formulation. METHODS: After a 2-wk baseline, 362 primary care
IBS patients, with any bowel habit subtype, were randomized to either placebo or
freeze-dried, encapsulated B. infantis at a dose of 1 x 10(6), 1 x 10(8), or 1 x
10(10), cfu/mL for 4 wk. IBS symptoms were monitored daily and scored on to a
6-point Likert scale with the primary outcome variable being abdominal pain or
discomfort. A composite symptom score, the subject's global assessment of IBS
symptom relief, and measures of quality of life (using the IBS-QOL instrument)
were also recorded. RESULTS: B. infantis 35624 at a dose of 1 x 10(8) cfu was
significantly superior to placebo and all other bifidobacterium doses for the
primary efficacy variable of abdominal pain as well as the composite score and
scores for bloating, bowel dysfunction, incomplete evacuation, straining, and
the passage of gas at the end of the 4-wk study. The improvement in global
symptom assessment exceeded placebo by more than 20% (p < 0.02). Two other doses
of probiotic (1 x 10(6) and 1 x 10(10)) were not significantly different from
placebo; of these, the 1 x 10(10) dose was associated with significant
formulation problems. No significant adverse events were recorded. CONCLUSIONS:
B. infantis 35624 is a probiotic that specifically relieves many of the symptoms
of IBS. At a dosage level of 1 x 10(8) cfu, it can be delivered by a capsule
making it stable, convenient to administer, and amenable to widespread use. The
lack of benefits observed with the other dosage levels of the probiotic
highlight the need for clinical data in the final dosage form and dose of
probiotic before these products should be used in practice.
-----
Aliment Pharmacol Ther. 2006 Jul 15;24(2):207-36.
Systematic review: the safety and tolerability of pharmacological
agents for treatment of irritable bowel syndrome--a European perspective.
Heading R, Bardhan K, Hollerbach S, Lanas A, Fisher G.
Royal Infirmary, Glasgow, UK. rheading@dialstart.net
AIM: To use an evidence-based approach to evaluate the safety and tolerability
of the treatments available for irritable bowel syndrome (IBS), or in clinical
development, in Europe. A separate review appraises the evidence for the
efficacy of these therapies. METHODS: A literature search (for 1980 to 2005) was
completed for all relevant clinical trial data and other articles which included
safety information on the use of pharmacological IBS therapies. Clinical trials
were scored according to the level of safety information, and adverse event
incidence reported when possible. RESULTS: The tolerability of many of the
agents used to treat IBS in Europe is poorly understood. However, serotonergic
agents, such as tegaserod and alosetron, which are currently unavailable in
Europe, have undergone rigorous assessment in IBS and their benefits have been
established. Following initial marketing of alosetron for use in patients with
IBS with diarrhoea, concerns about severe constipation and ischaemic colitis
resulted in restriction of its use to women with severe IBS symptoms. This
highlights the importance of post-marketing surveillance and post-marketing
studies in refining the therapeutic indication of new IBS therapies, which will
help to identify appropriate recipients for the drug and establish the impact of
adverse reactions in clinical practice. CONCLUSIONS: There is a significant lack
of data on the safety and tolerability of the therapies currently used routinely
to treat IBS in Europe. The newer agents have undergone rigorous assessment,
such that their benefits and risks in treating IBS are established. Defining
their place among the spectrum of available therapies remains challenging when
the benefits and risks of the older treatments are so poorly characterized.
-----
Aliment Pharmacol Ther. 2006 Jul 15;24(2):183-205.
Systematic review: the efficacy of treatments for irritable bowel
syndrome--a European perspective.
Tack J, Fried M, Houghton LA, Spicak J, Fisher G.
University Hospital of Leuven, Leuven, Belgium. jan.tack@med.kuleuven.be
BACKGROUND: Irritable bowel syndrome (IBS) is a common, chronic disorder,
characterized by abdominal pain/discomfort, bloating and altered bowel habit.
AIM: To conduct a systematic evidence-based review of pharmacological therapies
currently used, or in clinical development, for the treatment of IBS in Europe.
The safety and tolerability of these therapies are the subject of an
accompanying review. METHODS: A literature search was completed for randomized
controlled studies which included adult patients with IBS and an active or
placebo control, assessed IBS symptoms, and were published in English between
January 1980 and June 2005. The level of evidence for efficacy was graded
according to the quality of the trial design and the study outcome. RESULTS:
There is some evidence for improvement of individual IBS symptoms with
antidiarrhoeals (diarrhoea), antispasmodics (abdominal pain/discomfort), bulking
agents (constipation), tricyclic antidepressants (abdominal pain/discomfort) and
behavioural therapy. In contrast, there is strong evidence for the improvement
of global IBS symptoms with two new serotonergic agents: the 5-HT4 selective
agonist tegaserod (IBS with constipation) and the 5-HT3 antagonist alosetron
(IBS with diarrhoea). Further data are required for the 5-HT3 antagonist,
cilansetron, and the mixed 5-HT3 antagonist/5-HT4 agonist renzapride before
their utility in IBS can be appraised. CONCLUSIONS: There is limited evidence
for the efficacy, safety and tolerability of therapies currently available in
Europe for the treatment of IBS. Overall, there is an absence of pharmacological
agents licensed specifically for the treatment of IBS subtypes, and new agents
are awaited in Europe that will allow changes in clinical practice to focus on
and improve global IBS symptoms.
-----
Curr Treat Options Gastroenterol. 2006 Jul;9(4):314-23.
Current gut-directed therapies for irritable bowel syndrome.
Chang HY, Kelly EC, Lembo AJ.
Beth Israel Deaconess Medical Center/Harvard University Medical School, 330
Brookline Avenue, Dana 501, Boston, MA 02215, USA. alembo@bidmc.harvard.edu.
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that
can present with a wide array of symptoms that make treatment difficult. Current
therapies are directed at relieving symptoms of abdominal pain or discomfort,
bloating, constipation, and diarrhea. Pharmacologic agents used to treat
IBS-associated pain include myorelaxants, peppermint oil, and peripherally
acting opiates. Dicyclomine and hyoscyamine, the two myorelaxants available in
the United States, have not been proven effective in reducing abdominal pain in
patients with IBS. The efficacy of peppermint oil is debated, but methodological
problems with existing studies preclude definitive judgment. Loperamide is
ineffective for relief of abdominal pain. For IBS patients with excessive
abdominal bloating, a small number of studies suggest that bacterial eradication
with gut-directed antibiotics and bacterial reconstitution with nonpathogenic
probiotics may reduce flatulence. For constipation-predominant (C-IBS) symptoms,
current treatment options include fiber supplementation, polyethylene glycol,
and tegaserod. Soluble fibers (ispaghula, calcium polycarbophil, psyllium) are
more effective than insoluble fibers (wheat bran, corn fiber) in alleviating
global symptoms and relieving constipation, although fiber in general has
marginal benefit in treatment of overall IBS symptoms. Polyethylene glycol
increases bowel frequency in chronic constipation, but its overall efficacy
against IBS is unclear. Tegaserod, a 5-HT(4) agonist, demonstrates superiority
over placebo in improving bowel frequency and stool consistency and alleviating
abdominal pain and bloating in women with C-IBS. Overall global symptoms are
modestly improved with tegaserod when compared with placebo. Additional agents
under investigation for C-IBS include the ClC(2) chloride channel opener
lubiprostone, mu-opioid receptor antagonist alvimopan, and 5-HT(4) agonist
renzapride. For diarrhea-predominant (D-IBS) symptoms, available therapies
include loperamide, alosetron, and clonidine. Alosetron, a 5-HT(3) antagonist,
is superior to placebo for reducing bowel frequency, improving stool
consistency, and relieving abdominal pain in women with D-IBS. However,
alosetron is available under a restricted license because of concerns for
ischemic colitis and severe constipation necessitating colectomy. Clonidine may
be helpful in alleviating global symptoms for D-IBS patients.
-----
J Gastroenterol. 2006 May;41(5):408-17.
Acupuncture for functional gastrointestinal disorders.
Takahashi T.
Department of Surgery, Duke University Medical Center, Durham, NC 27705, USA.
Functional gastrointestinal (GI) symptoms are common in the general population.
Especially, motor dysfunction of the GI tract and visceral hypersensitivity are
important. Acupuncture has been used to treat GI symptoms in China for thousands
of years. It is conceivable that acupuncture may be effective in patients with
functional GI disorders because it has been shown to alter acid secretion, GI
motility, and visceral pain. Acupuncture at the lower limbs (ST-36) causes
muscle contractions via the somatoparasympathetic pathway, while at the upper
abdomen (CV-12) it causes muscle relaxation via the somatosympathetic pathway.
In some patients with gastroesophageal reflux disease (GERD) and functional
dyspepsia (FD), peristalsis and gastric motility are impaired. The stimulatory
effects of acupuncture at ST-36 on GI motility may be beneficial to patients
with GERD or FD, as well as to those with constipation-predominant irritable
bowel syndrome (IBS), who show delayed colonic transit. In contrast, the
inhibitory effects of acupuncture at CV-12 on GI motility may be beneficial to
patients with diarrhea-predominant IBS, because enhanced colonic motility and
accelerated colonic transit are reported in such patients. Acupuncture at CV-12
may inhibit gastric acid secretion via the somatosympathetic pathway. Thus,
acupuncture may be beneficial to GERD patients. The antiemetic effects of
acupuncture at PC-6 (wrist) may be beneficial to patients with FD, whereas the
antinociceptive effects of acupuncture at PC-6 and ST-36 may be beneficial to
patients with visceral hypersensitivity. In the future, it is expected that
acupuncture will be used in the treatment of patients with functional GI
disorders.
-----
Drugs. 2006;66(8):1073-88.
Irritable bowel syndrome: recent and novel therapeutic
approaches.
Andresen V, Camilleri M.
Clinical Enteric Neuroscience Translational and Epidemiological Research
(CENTER) Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905,
USA. Andresen.Viola@mayo.edu
Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal
disorder affecting up to 3-15% of the general population in Western countries.
It is characterised by unexplained abdominal pain, discomfort and bloating in
association with altered bowel habits. The pathophysiology of IBS is considered
to be multifactorial, involving disturbances of the brain-gut-axis: IBS has been
associated with abnormal gastrointestinal motor functions, visceral
hypersensitivity, psychosocial factors, autonomic dysfunction and mucosal
inflammation. Traditional IBS therapy is mainly symptom oriented and often
unsatisfactory. Hence, there is a need for new treatment strategies. Increasing
knowledge of brain-gut physiology, mechanisms, and neurotransmitters and
receptors involved in gastrointestinal motor and sensory function have led to
the development of several new therapeutic approaches. This article provides a
systematic overview of recently approved or novel medications that show promise
for the treatment of IBS; classification is based on the physiological systems
targeted by the medication. The article includes agents acting on the serotonin
receptor or serotonin transporter system, novel selective anticholinergics,
alpha-adrenergic agonists, opioid agents, cholecystokinin antagonists,
neurokinin antagonists, somatostatin receptor agonists, neurotrophin-3,
corticotropin releasing factor antagonists, chloride channel activators,
guanylate cyclase-c agonists, melatonin and atypical benzodiazepines. Finally,
the role of probiotics and antibacterials in the treatment of IBS is summarised.
-----
Phytother Res. 2006 Jun 12; [Epub ahead of print]
A review of the bioactivity and potential health benefits of
peppermint tea (Mentha piperita L.).
McKay DL, Blumberg JB.
USDA Human Nutrition Research Center on Aging at Tufts University, 711
Washington St., Boston, MA 02111, USA.
Peppermint (Mentha piperita L.) is one of the most widely consumed single
ingredient herbal teas, or tisanes. Peppermint tea, brewed from the plant
leaves, and the essential oil of peppermint are used in traditional medicines.
Evidence-based research regarding the bioactivity of this herb is reviewed. The
phenolic constituents of the leaves include rosmarinic acid and several
flavonoids, primarily eriocitrin, luteolin and hesperidin. The main volatile
components of the essential oil are menthol and menthone. In vitro, peppermint
has significant antimicrobial and antiviral activities, strong antioxidant and
antitumor actions, and some antiallergenic potential. Animal model studies
demonstrate a relaxation effect on gastrointestinal (GI) tissue, analgesic and
anesthetic effects in the central and peripheral nervous system,
immunomodulating actions and chemopreventive potential. Human studies on the GI,
respiratory tract and analgesic effects of peppermint oil and its constituents
have been reported. Several clinical trials examining the effects of peppermint
oil on irritable bowel syndrome (IBS) symptoms have been conducted. However,
human studies of peppermint leaf are limited and clinical trials of peppermint
tea are absent. Adverse reactions to peppermint tea have not been reported,
although caution has been urged for peppermint oil therapy in patients with GI
reflux, hiatal hernia or kidney stones. Copyright (c) 2006 John Wiley & Sons,
Ltd.
-----
Expert Opin Drug Saf. 2006 Mar;5(2):313-27.
The rationale, efficacy and safety evidence for tegaserod in the
treatment of irritable bowel syndrome.
McLaughlin J, Houghton LA.
Department of Gastroenterology, Hope Hospital, Salford, Manchester, M6 8HD, UK.
A growing body of evidence implicates abnormal serotonergic regulation of
gastrointestinal function in the pathogenesis of the irritable bowel syndrome
(IBS). Drugs targeting this system are therefore attractive concepts. The
partial 5-HT4 receptor agonist tegaserod might be predicted to have positive
therapeutic effects on a constipated and uncomfortable gut. However, IBS runs a
chronic, benign course and carries no associated mortality, so it is imperative
that the safety profile of new pharmacological agents made available to
physicians is exemplary. The authors review the evidence for 5-HT in the
aetiology of IBS and its symptoms, and the data available concerning the partial
5-HT4 receptor agonist tegaserod, in terms of rationale, efficacy and safety.
-----
Curr Opin Gastroenterol. 2006 Mar;22(2):128-35.
Irritable bowel syndrome: new and emerging therapies.
Harris LA, Chang L.
Mayo Clinic College of Medicine, Scottsdale, Arizona, USA.
PURPOSE OF REVIEW: Irritable bowel syndrome refers to abdominal discomfort
associated with altered bowel habits. Recent evidence suggests that the primary
pathophysiologic mechanism is brain-gut dysregulation. Many central and
peripheral factors are involved. This article will review important
pathophysiologic mechanisms with a focus on new and emerging therapies. RECENT
FINDINGS: Prior gastroenteritis and small intestinal bacterial overgrowth may be
important for treatment of irritable bowel syndrome. Understanding of
serotonergic receptors in gastrointestinal function has led to the development
of serotonergic agents such as alosetron and tegaserod. Novel agents targeting
other receptor sites include neurokinin and neurohormonal modulators, chloride
channels and opioid receptors. Other therapeutic approaches - behavioral
treatments, probiotics, antibiotics and alternative therapies - have developing
roles in the treatment of irritable bowel syndrome. SUMMARY: A better
understanding of pathophysiologic mechanisms has resulted in therapeutic
advances. Prokinetic therapies may have a role in nondiarrhea predominant
irritable bowel syndrome. Antidepressants are used to modulate pain and treat
comorbid psychological distress. Newer agents target various receptor sites.
Advances in psychological/behavioral treatments and alternative modalities hold
promise for the future.
-----
Nutrition. 2006 Mar;22(3):334-42. Epub 2006 Jan 18.
Role of partially hydrolyzed guar gum in the treatment of
irritable bowel syndrome.
Giannini EG, Mansi C, Dulbecco P, Savarino V.
Gastroenterology Unit, Department of Internal Medicine, University of Genoa,
Genoa, Italy.
Irritable bowel syndrome (IBS) is the world's most common gastrointestinal
functional disorder and is associated with several social and economic costs.
Health-related quality of life is often impaired in patients with IBS. The
pathophysiologic mechanisms underlying IBS remain poorly defined. The
therapeutic approach to patients with IBS is based on symptoms, and fibers may
play an important role in treatment. Among the various types of fiber,
water-soluble, non-gelling fibers seem to be a promising option for treatment of
IBS. Partially hydrolyzed guar gum (PHGG) is a water-soluble, non-gelling fiber
that has provided therapeutic benefits. In clinical trials, PHGG decreased
symptoms in constipation-predominant and diarrhea-predominant forms of IBS and
decreased abdominal pain. Further, an improvement in quality of life was
observed in patients with IBS during and after treatment with PHGG. Moreover,
PHGG seems to have prebiotic properties because it increases the colonic
contents of short-chain fatty acids, Lactobacilli, and Bifidobacteria.
-----
World J Gastroenterol. 2006 Feb 14;12(6):853-7.
Probiotics and the gastrointestinal tract: Where are we in 2005?
Chermesh I, Eliakim R.
Gastroenterology Department, Rambam Medical Center, P.O.B 9602, Haifa 31096,
Israel. r_eliakim@rambam.health.gov.il.
Probiotic agents are live microbes or components of microbes that have a
positive effect on the host. They exert their action through interplay with the
immune system of the host. Some of this effect is local and some is systemic.
The full story is yet to be discovered. Probiotics have a definite positive
effect on rotavirus diarrhea, post antibiotic diarrhea and pouchitis. Their
exact role in inflammatory bowel disease, irritable bowel syndrome, other forms
of infectious diarrhea, and prevention of cancer is yet to be determined. This
review summarizes the data about probiotics in these conditions.
-----
J Clin Gastroenterol. 2006 Feb;40(2):104-8.
The role of fiber in the treatment of irritable bowel syndrome:
therapeutic recommendations.
Zuckerman MJ.
Division of Gastroenterology, Texas Tech University Health Sciences Center, El
Paso, TX 79905, USA. Marc.Zuckerman@ttuhsc.edu
Irritable bowel syndrome is a common clinical condition that often presents a
therapeutic challenge. There is no standard therapy and a multilevel approach is
recommended. A high-fiber diet is often one of these components. Many
investigators have studied the effectiveness of either fiber supplementation or
bulking agents in patients with irritable bowel syndrome. The purpose of this
review is to summarize the current literature on the use of fiber in irritable
bowel syndrome and to provide some specific recommendations. Systematic reviews
of these trials have generally not found fiber to be significantly more
effective than placebo at relieving global irritable bowel syndrome symptoms.
There may be differences between results obtained with soluble and insoluble
fiber. Adverse effects of fiber use may include abdominal discomfort and
bloating. Although dietary fiber or bulking agents do not appear to be useful as
sole treatment of irritable bowel syndrome, they may have a limited role in
empiric therapy depending upon the patient's symptom complex, especially if
constipation is the most significant symptom. The basic principles for using
fiber therapy are to start with a low dose and increase slowly, to give an
adequate trial and to evaluate the results early and periodically.
-----
Aliment Pharmacol Ther. 2006 Feb 15;23(4):465-71.
Systematic review: Complementary and alternative medicine in the
irritable bowel syndrome.
Hussain Z, Quigley EM.
Department of Medicine, Alimentary Pharmabiotic Centre, Cork University
Hospital, Cork, Ireland.
BACKGROUND: Complementary and alternative medical therapies and practices are
widely employed in the treatment of the irritable bowel syndrome. AIM: To review
the usage of complementary and alternative medicine in the irritable bowel
syndrome, and to assess critically the basis and evidence for its use. METHODS:
A systematic review of complementary and alternative medical therapies and
practices in the irritable bowel syndrome was performed based on literature
obtained through a Medline search. RESULTS: A wide variety of complementary and
alternative medical practices and therapies are commonly employed by irritable
bowel syndrome patients both in conjunction with and in lieu of conventional
therapies. As many of these therapies have not been subjected to controlled
clinical trials, some, at least, of their efficacy may reflect the high-placebo
response rate that is characteristic of irritable bowel syndrome. Of those that
have been subjected to clinical trials most have involved small poor quality
studies. There is, however, evidence to support efficacy for hypnotherapy, some
forms of herbal therapy and certain probiotics in irritable bowel syndrome.
CONCLUSIONS: Doctors caring for irritable bowel syndrome patients need to
recognize the near ubiquity of complementary and alternative medical use among
this population and the basis for its use. All complementary and alternative
medicine is not the same and some, such as hypnotherapy, forms of herbal
therapy, specific diets and probiotics, may well have efficacy in irritable
bowel syndrome. Above all, we need more science and more controlled studies; the
absence of truly randomized placebo-controlled trials for many of these
therapies has limited meaningful progress in this area.
-----
Digestion. 2006;73 Suppl 1:28-37. Epub 2006 Feb 8.
Pharmacological treatment of the irritable bowel syndrome and
other functional bowel disorders.
Mearin F.
Institute of Functional and Motor Digestive Disorders, Centro Medico Teknon,
Barcelona, Spain. mearin@dr.teknon.es
Functional digestive disorders constitute one of the main causes of consultation
in gastroenterology and primary health care. Is still unclear whether therapy
has to be aimed to the gut, to the neural pathways controlling bowel motility
and perception, or to the processing mechanisms of symptoms and disease
behaviour. It is conceivable that in the next future better understanding of
functional bowel disorders pathophysiology will help us to tailor treatment for
different patients. At the moment, subclassification of the diverse patterns of
symptomatology allows to adjust new treatments for irritable bowel syndrome
(IBS) according to the clinical predominance for each patient. The knowledge of
motor and sensorial response to different stimuli in IBS patients and the
pathways to the central nervous system is an important source of information for
the development of new molecules. Fiber-enriched diet is frequently given for
constipation-predominant IBS. Loperamide, antispasmodic drugs and tricyclic
antidepressants are nowadays the basis for pharmacological treatment of
diarrhea- predominant IBS. The scientific evidence supporting this therapeutical
approach is however limited. Visceral analgesics and serotonin agonists and
antagonists may play an important therapeutical role in the near future.
However, it is not likely that one single treatment will help every functional
bowel disorder patient and many of them will need a more complex approach with a
multidisciplinary therapy (diet, psychotherapy, medications). Copyright 2006 S.
Karger AG, Basel.
-----
Br J Gen Pract. 2006 Feb;56(523):115-21.
Gut-directed hypnotherapy for irritable bowel syndrome: piloting
a primary care-based randomised controlled trial.
Roberts L, Wilson S, Singh S, Roalfe A, Greenfield S.
Department of Primary Care and General Practice, Division of Primary Care,
Public and Occupational Health, University of Birmingham, Edgbaston, Birmingham
B15 2TT, UK. robertslz@adf.bham.ac.uk
BACKGROUND: In western populations irritable bowel syndrome (IBS) affects
between 10% and 30% of the population and has a significant effect on quality of
life. It generates a substantial workload in both primary and secondary care and
has significant cost implications. Gut-directed hypnotherapy has been
demonstrated to alleviate symptoms and improve quality of life but has not been
assessed outside of secondary and tertiary referral centres. AIM: To assess the
effectiveness of gut-directed hypnotherapy as a complementary therapy in the
management of IBS. DESIGN OF STUDY: Randomised controlled trial. SETTING:
Primary care patients aged 18-65 years inclusive, with a diagnosis of IBS of
greater than 6 weeks' duration and having failed conventional management,
located in South Staffordshire and North Birmingham, UK. METHOD: Intervention
patients received five sessions of hypnotherapy in addition to their usual
management. Control patients received usual management alone. Data regarding
symptoms and quality of life were collected at baseline and again 3, 6, and 12
months post-randomisation. RESULTS: Both groups demonstrated a significant
improvement in all symptom dimensions and quality of life over 12 months. At 3
months the intervention group had significantly greater improvements in pain,
diarrhoea and overall symptom scores (P<0.05). No significant differences
between groups in quality of life were identified. No differences were
maintained over time. Intervention patients, however, were significantly less
likely to require medication, and the majority described an improvement in their
condition. CONCLUSIONS: Gut-directed hypnotherapy benefits patients via symptom
reduction and reduced medication usage, although the lack of significant
difference between groups beyond 3 months prohibits its general introduction
without additional evidence. A large trial incorporating robust economic
analysis is, therefore, urgently recommended.
-----
Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004116.
Herbal medicines for treatment of irritable bowel syndrome.
Liu J, Yang M, Liu Y, Wei M, Grimsgaard S.
BACKGROUND: Traditional herbal therapies have been used for a long time to treat
gastrointestinal disorders including irritable bowel syndrome, and their
effectiveness from clinical research evidence needs to be systematically
reviewed. OBJECTIVES: To assess the effectiveness and safety of herbal medicines
in patients with irritable bowel syndrome. SEARCH STRATEGY: We searched the
following electronic databases till July 2004: The Cochrane Library (CENTRAL),
MEDLINE, EMBASE, AMED, LILACS, the Chinese Biomedical Database, combined with
hand searches of Chinese journals and conference proceedings till end of 2003.
No language restriction was used. SELECTION CRITERIA: Randomised controlled
trials of herbal medicines compared with no treatment, placebo, pharmacological
interventions were included. DATA COLLECTION AND ANALYSIS: Data were extracted
independently by two authors. The methodological quality of trials was evaluated
using the components of randomisation, allocation concealment, double blinding,
and inclusion of randomised participants. MAIN RESULTS: Seventy-five randomised
trials, involving 7957 participants with irritable bowel syndrome, met the
inclusion criteria. The methodological quality of three double-blind,
placebo-controlled trials was high, but the quality of remaining trials was
generally low. Seventy-one different herbal medicines were tested in the
included trials, in which herbal medicines were compared with placebo or
conventional pharmacologic therapy. Herbal medicines were also combined with
conventional therapy and compared to conventional therapy alone.Compared with
placebo, a Standard Chinese herbal formula, individualised Chinese herbal
medicine, STW 5 and STW 5-II, Tibetan herbal medicine Padma Lax, traditional
Chinese formula Tongxie Yaofang, and Ayurvedic preparation showed significantly
improvement of global symptoms. Compared with conventional therapy in 65 trials
testing 51 different herbal medicines, 22 herbal medicines demonstrated a
statistically significant benefit for symptom improvement, and 29 herbal
medicines were not significantly different than conventional therapy. In nine
trials that evaluated herbal medicine combined with conventional therapy, six
tested herbal preparations showed additional benefit from the combination
therapy compared with conventional monotherapy. No serious adverse events from
the herbal medicines were reported. AUTHORS' CONCLUSIONS: Some herbal medicines
may improve the symptoms of irritable bowel syndrome. However, positive findings
from less rigorous trials should be interpreted with caution due to inadequate
methodology, small sample sizes, and lack of confirming data. Some herbal
medicines deserve further examination in high-quality trials.
-----
Gut. 2006 Jan 9; [Epub ahead of print]
A controlled cross-over study of the selective serotonin reuptake
inhibitor citalopram in irritable bowel syndrome.
Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers A, Janssens J.
University Hospital Gasthuisberg, Belgium.
INTRODUCTION: Selective Serotonin Reuptake Inhibitors (SSRIs) are frequently
used in the treatment of irritable bowel syndrome (IBS), although evidence of
their efficacy is scarce. AIM: Twenty three non-depressed IBS patients were
recruited from a tertiary care center and included in a crossover trial
comparing 6 weeks treatment with the SSRI citalopram (3 weeks 20 mg, 3 weeks 40
mg) with placebo. IBS symptom severity was the primary outcome measure, and
depression and anxiety scores were also measured. The effect of acute
administration of citalopram on colonic sensitivity and on colonic response to
feeding was investigated as a putative predictor of symptomatic response to the
drug. RESULTS: After 3 and 6 weeks treatment, citalopram significantly improved
abdominal pain, bloating, impact of symptoms on daily life and overall
well-being, compared to placebo. There was only a modest effect on stool
pattern. Changes in depression or anxiety scores were not related to symptom
improvement. The effect of acute administration of citalopram during a colonic
barostat study did not predict clinical outcome. Analysis of the first treatment
period as a double-blind parallel- arm study confirmed the benefit of citalopram
over placebo. CONCLUSIONS: The SSRI citalopram significantly improves IBS
symptoms including abdominal pain, compared to placebo. The therapeutic effect
is independent of effects on anxiety, depression and colonic sensorimotor
funciton.
-----
Curr Opin Gastroenterol. 2006 Jan;22(1):13-7
Post-infectious irritable bowel syndrome.
Spiller R, Campbell E.
Wolfson Digestive Diseases Centre, University Hospital, Nottingham, UK.
PURPOSE OF REVIEW: Irritable bowel syndrome patients form a heterogeneous group
with a variable contribution of central and peripheral components. The
peripheral component is prominent in irritable bowel syndrome developing after
infection (post-infectious irritable bowel syndrome) and this has proved a
profitable area of research. RECENT FINDINGS: Recent studies have overthrown the
dogma that irritable bowel syndrome is characterized by no abnormality of
structure by demonstrating low-grade lymphocytic infiltration in the gut mucosa,
increased permeability and increases in other inflammatory components including
enterochromaffin and mast cells. Furthermore, increased inflammatory cytokines
in both mucosa and blood have been demonstrated in irritable bowel syndrome.
While steroid treatment has proved ineffective, preliminary studies with
probiotics exerting an anti-inflammatory effect have shown benefit. SUMMARY: The
study of post-infectious irritable bowel syndrome has revealed the importance of
low-grade inflammation in causing irritable bowel syndrome symptoms. It has
suggested novel approaches to irritable bowel syndrome including studies of
serotonin and histamine metabolism which may be relevant to other subtypes of of
the disease.
-----
Int J Clin Exp Hypn. 2006 Jan;54(1):85-99.
Hypnosis home treatment for irritable bowel syndrome: a pilot
study.
Palsson OS, Turner MJ, Whitehead WE.
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Hypnosis treatment often improves irritable bowel syndrome (IBS), but the costs
and reliance on specialized therapists limit its availability. A 3-month
home-treatment version of a scripted hypnosis protocol previously shown to
improve all central IBS symptoms was completed by 19 IBS patients. Outcomes were
compared to those of 57 matched IBS patients from a separate study receiving
only standard medical care. Ten of the hypnosis subjects (53%) responded to
treatment by 3-month follow-up (response defined as more than 50% reduction in
IBS severity) vs. 15 (26%) of controls. Hypnosis subjects improved more in
quality of life scores compared to controls. Anxiety predicted poor treatment
response. Hypnosis responders remained improved at 6-month follow-up. Although
response rate was lower than previously observed in therapist-delivered
treatment, hypnosis home treatment may double the proportion of IBS patients
improving significantly across 6 months.
-----
Int J Clin Exp Hypn. 2006 Jan;54(1):51-64.
Standardized hypnosis treatment for irritable bowel syndrome: the
north Carolina protocol.
Palsson OS.
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
The North Carolina protocol is a seven-session hypnosis-treatment approach for
irritable bowel syndrome that is unique in that the entire course of treatment
is designed for verbatim delivery. The protocol has been tested in two published
research studies and found to benefit more than 80% of patients. This article
describes the development, content, and testing of the protocol, and how it is
used in clinical practice.
-----
Int J Clin Exp Hypn. 2006 Jan;54(1):7-20.
Hypnosis for irritable bowel syndrome: the empirical evidence of
therapeutic effects.
Whitehead WE.
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Irritable bowel syndrome (IBS) is a complex and prevalent functional
gastrointestinal disorder that is treated with limited effectiveness by standard
medical care. Hypnosis treatment is, along with cognitive-behavioral therapy,
the psychological therapy best researched as an intervention for IBS. Eleven
studies, including 5 controlled studies, have assessed the therapeutic effects
of hypnosis for IBS. Although this literature has significant limitations, such
as small sample sizes and lack of parallel comparisons with other treatments,
this body of research consistently shows hypnosis to have a substantial
therapeutic impact on IBS, even for patients unresponsive to standard medical
interventions. The median response rate to hypnosis treatment is 87%, bowel
symptoms can generally be expected to improve by about half, psychological
symptoms and life functioning improve after treatment, and therapeutic gains are
well maintained for most patients for years after the end of treatment.
-----
Curr Opin Pharmacol. 2005 Dec;5(6):596-603. Epub 2005 Oct 7.
Probiotics and nutraceuticals: non-medicinal treatments of
gastrointestinal diseases.
Penner R, Fedorak RN, Madsen KL.
Division of Gastroenterology, University of Alberta, 6146 Dentistry Pharmacy,
Edmonton, Alberta T6G 2N8, Canada.
The demonstration that immune and epithelial cells can discriminate between
different microbial and bioactive plant species has extended the known
mechanism(s) of action of nutraceuticals and probiotics beyond simple nutrition
and/or antimicrobial effects. The progressive unravelling of these plant and
bacterial effects on systemic immune and intestinal epithelial cell function has
led to new credence for the use of probiotics and nutraceuticals in clinical
medicine. Level I evidence now exists for the therapeutic use of probiotics in
infectious diarrhea in children, recurrent Clostridium difficile-induced
infections and post-operative pouchitis. Additional evidence is being acquired
for the use of probiotics in other gastrointestinal infections, irritable bowel
syndrome and inflammatory bowel disease. Not all individual probiotic strains
have the same efficacy, and future clinical trials may focus on multistrain
preparations agents with known efficacy. The use of nutraceuticals and
probiotics as therapeutic agents for gastrointestinal disorders is rapidly
moving into clinical usage. Scientific studies are providing mechanisms of
action to explain the therapeutic effects, and randomized controlled trials are
providing the necessary evidence for their incorporation into the therapeutic
armamentarium.
-----
CNS Spectr. 2005 Nov;10(11):883-90.
Cognitive-behavioral treatment of irritable bowel syndrome.
Toner BB.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
There is increasing evidence that supports the view that irritable bowel
disorder (IBS) is a disorder of brain-gut function. Cognitive-behavioral therapy
(CBT) has received increased attention in light of this recent shift in the
conceptualization of IBS. This review has two main aims. The first is to provide
a critical review of controlled trials on CBT for IBS. The second is to discuss
ways of further developing CBT interventions that are more clinically relevant
and meaningful to health care providers and individuals with a diagnosis of IBS.
A theme from a CBT intervention will be presented to illustrate how CBT
interventions can be incorporated within a larger social context. A review of
CBT for IBS lends some limited support for improvement in some IBS symptoms and
associated psychosocial distress. This conclusion needs to be expressed with
some caution, however, in light of many methodological shortcomings including
small sample sizes, inadequate control conditions and failure to identify
primary versus secondary outcome measures. In addition, future studies will need
to further develop more relevant CBT protocols that more fully integrate the
patient's perspective and challenge social cognitions about this stigmatized
disorder.
-----
Aliment Pharmacol Ther. 2005 Nov 15;22(10):927-34.
Melatonin improves bowel symptoms in female patients with
irritable bowel syndrome: a double-blind placebo-controlled study.
Lu WZ, Gwee KA, Moochhalla S, Ho KY.
Department of Pharmacology, National University of Singapore.
BACKGROUND: Melatonin is involved in the regulation of gastrointestinal motility
and sensation. AIM : To determine the potential therapeutic effects of melatonin
in irritable bowel syndrome (IBS). METHOD: Seventeen female patients satisfying
the Rome II criteria for IBS were randomized to receive either melatonin 3 mg
nocte or identically appearing placebo 1 nocte for 8 weeks, followed by a 4-week
washout period and placebo or melatonin in the reverse order for another 8
weeks. Three validated questionnaires - the GI symptom, the sleep questionnaires
and the Hospital Anxiety and Depression Scale - were used to assess symptom
severity and to compute the IBS, sleep and anxiety/depression scores,
respectively. RESULTS: Improvements in mean IBS scores were significantly
greater after treatment with melatonin (3.9 +/- 2.6) than with placebo (1.3 +/-
4.0, P = 0.037). Percent response rate, defined as percentage of subjects
achieving mild-to-excellent improvement in IBS symptoms, was also greater in the
melatonin-treated arm (88% vs. 47%, P = 0.04). The changes in mean sleep,
anxiety, and depression scores were similar with either melatonin or placebo
treatment. CONCLUSIONS: Melatonin is a promising therapeutic agent for IBS. Its
therapeutic effect is independent of its effects on sleep, anxiety or
depression.
-----
Curr Opin Gastroenterol. 2005 Nov;21(6):697-701.
Irritable bowel syndrome and probiotics: from rationale to
clinical use.
Verdu EF, Collins SM.
Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario,
Canada.
PURPOSE OF REVIEW: Few therapies are of proven efficacy in irritable bowel
syndrome. Thus, there is great interest in the development of a natural therapy
that can be both safe and effective. An understanding that probiotics are
heterogeneous, with multiple targets and mechanisms of action, is fundamental to
the development of clinical trials. RECENT FINDINGS: A bidirectional model for
the pathogenesis of irritable bowel syndrome is proposed in which gut-driven and
brain-driven mechanisms contribute to the genesis of gut dysfunction and
symptoms. In-vitro and animal studies have generated most of the mechanistic
rationale for the use of probiotics in functional bowel disorders. A MEDLINE
search of publications from 1989 to date revealed only eight placebo-controlled
clinical trials on the subject of probiotics and irritable bowel syndrome. All
these studies suffer from methodologic problems. By contrast, numerous reviews
have been published in the past 2 years on this subject. SUMMARY: Animal
research will continue to identify novel targets and elucidate the mechanisms of
action of probiotics, thus providing a rational basis for their use in irritable
bowel syndrome. The notion of treating irritable bowel syndrome with probiotics
is particularly attractive to patients and generates great interest, although
clinical evidence is not yet sufficient to enable clear guidelines to be
designed. Large, well-designed, controlled clinical trials using specific
probiotics are warranted.
-----
Gastroenterol Hepatol. 2005 Oct;28(8):485-92.
[Antidepressant therapy in functional gastrointestinal disorders]
[Article in Spanish]
Bixquert-Jimenez M, Bixquert-Pla L.
Servicio de Digestivo, Hospital Arnau de Vilanova, Valencia, Spain.
miguel.bixquert@uv.es
The available evidence from randomized clinical trials or meta-analyses on the
therapeutic efficacy of psychotropic drugs and, specifically, of
antidepressants, in functional gastrointestinal disorders (FGD), are recent and
still fairly limited. The use of these drugs is based on the frequent
association of anxiety and depression or neurosis in patients with FGD who seek
medical care and on the demonstrated efficacy of these drugs in relieving
chronic pain, whatever its origin or localization, for more than 30 years.
Antidepressants, even in doses under the antidepressant range, are
antinociceptive due to their central and peripheral neuromodulatory effect,
which is completely independent of anticholinergic, spasmolytic or
antidepressant effects. This has been demonstrated in both animals and humans
and, as occurs with another antinociceptive drugs such as clonidine, is mediated
by alpha-adrenoreceptors. The choice of antidepressant depends both on the
evidence of its analgesic activity (in general greater with tricyclic
antidepressants than with the more modern selective serotonin reuptake
inhibitors) and on the presence of drug-related adverse effects, which include
not only anticholinergic adverse effects but also the possibility of hypotension
or cardiotoxicity, which should be avoided. The main selection criteria are
demonstrated efficacy and safety. Antidepressants have been shown to be
effective in the specific field of non-coronary chest pain probably originating
in the esophagus unrelated to gastroesophageal reflux disease, especially
mianserin and trazodone, and the effect is maintained in the long term in nearly
three-quarters of treated patients. Tricyclic antidepressants have also been
shown to be effective in the treatment of abdominal pain in patients with
irritable bowel syndrome, with an OR of 4.2 and an NNT of 3.2 in comparison with
placebo. In contrast, there is insufficient evidence to recommend the use of
antidepressants in functional dyspepsia.
-----
Neurogastroenterol Motil. 2005 Oct;17(5):687-96.
A randomized controlled trial of a probiotic combination VSL# 3
and placebo in irritable bowel syndrome with bloating.
Kim HJ, Vazquez Roque MI, Camilleri M, Stephens D, Burton DD, Baxter K,
Thomforde G, Zinsmeister AR.
Clinical Enteric Neuroscience Translational and Epidemiological Research
(CENTER) Group, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
AIM: To evaluate the effects of a combination probiotic on symptoms and colonic
transit in patients with irritable bowel syndrome (IBS) and significant
bloating. METHODS: Forty-eight patients with Rome II IBS were randomized in a
parallel group, double-blind design to placebo or VSL# 3 twice daily (31
patients received 4 weeks and 17 patients 8 weeks of treatment). Pre- and
post-treatment colonic transit measurements were performed using scintigraphy
with (111)In charcoal. Symptoms were summarized as an average daily score for
the entire period of treatment and separately for the first 4 weeks of
treatment. Weekly satisfactory relief of abdominal bloating was assessed.
RESULTS: Treatment with VSL# 3 was associated with reduced flatulence over the
entire treatment period (placebo 39.5 +/- 2.6 vs VSL# 3 29.7 +/- 2.6, P =
0.011); similarly, during the first 4 weeks of treatment, flatulence scores were
reduced (placebo 40.1 +/- 2.5 vs VSL# 3 30.8 +/- 2.5, P = 0.014). Proportions of
responders for satisfactory relief of bloating, stool-related symptoms,
abdominal pain and bloating scores were not different. Colonic transit was
retarded with VSL# 3 relative to placebo (colon geometric center 2.27 +/- 0.20
vs 2.83 +/- 0.19, P = 0.05 respectively). CONCLUSION: VSL# 3 reduces flatulence
scores and retards colonic transit without altering bowel function in patients
with IBS and bloating.
-----
Neurogastroenterol Motil. 2005 Oct;17(5):687-96.
A randomized controlled trial of a probiotic combination VSL# 3
and placebo in irritable bowel syndrome with bloating.
Kim HJ, Vazquez Roque MI, Camilleri M, Stephens D, Burton DD, Baxter K,
Thomforde G, Zinsmeister AR.
Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.)
Group, Mayo Clinic College of Medicine, Rochester, MN, USA.
Aim: To evaluate the effects of a combination probiotic on symptoms and colonic
transit in patients with irritable bowel syndrome (IBS) and significant
bloating. Methods: Forty-eight patients with Rome II IBS were randomized in a
parallel group, double-blind design to placebo or VSL# 3 twice daily (31
patients received 4 weeks and 17 patients 8 weeks of treatment). Pre- and
post-treatment colonic transit measurements were performed using scintigraphy
with (111)In charcoal. Symptoms were summarized as an average daily score for
the entire period of treatment and separately for the first 4 weeks of
treatment. Weekly satisfactory relief of abdominal bloating was assessed.
Results: Treatment with VSL# 3 was associated with reduced flatulence over the
entire treatment period (placebo 39.5 +/- 2.6 vs VSL# 3 29.7 +/- 2.6, P =
0.011); similarly, during the first 4 weeks of treatment, flatulence scores were
reduced (placebo 40.1 +/- 2.5 vs VSL# 3 30.8 +/- 2.5, P = 0.014). Proportions of
responders for satisfactory relief of bloating, stool-related symptoms,
abdominal pain and bloating scores were not different. Colonic transit was
retarded with VSL# 3 relative to placebo (colon geometric center 2.27 +/- 0.20
vs 2.83 +/- 0.19, P = 0.05 respectively). Conclusion: VSL# 3 reduces flatulence
scores and retards colonic transit without altering bowel function in patients
with IBS and bloating.
-----
Curr Opin Pharmacol. 2005 Sep 23; [Epub ahead of print]
Gastrointestinal pharmacology: irritable bowel syndrome.
Bueno L.
Neurogastroenterology Unit INRA, 180 Chemin de Tournefeuille-BP3, 31931
Toulouse, France.
Over the past 30 years, the main treatment of irritable bowel syndrome has aimed
to normalize gastrointestinal transit using either laxatives or antidiarrheal
agents, with or without the concurrent use of spasmolytics. The recent
introduction of serotonin-related drugs has stimulated investigations into the
pathophysiology of irritable bowel syndrome, including an evaluation of visceral
sensitivity. At the same time, more information has been acquired on the status
of the local immune system as a possible cause for sensitization of nerve
terminals. Such investigations have stimulated the emergence of new concepts and
original candidate drugs for the treatment of this functional disorder.
Particular attention is devoted to the correction of visceral hyperalgesia.
-----
Aust N Z J Psychiatry. 2005 Sep;39(9):807-15.
Does psychological treatment help only those patients with severe
irritable bowel syndrome who also have a concurrent
psychiatric disorder?
Creed F, Guthrie E, Ratcliffe J, Fernandes L, Rigby C, Tomenson B, Read N,
Thompson DG; North of England IBS Research Group.
School of Psychiatry and Behavioural Science, University of Manchester, Rawnsley
Building, Oxford Road, Manchester M13 9WL, UK. francis.creed@manchester.ac.uk
OBJECTIVE: We have previously reported improved health-related quality of life
in patients with severe irritable bowel syndrome (IBS) following psychological
treatments. In this paper, we examine whether this improvement was associated
with improvement in psychological symptoms and was confined to those patients
who had concurrent psychiatric disorder. METHOD: Two hundred and fifty-seven
patients with severe IBS entering a psychological treatment trial were
interviewed using the Schedules for Clinical Assessment in Neuropsychiatry. At
entry to the trial and 15 months later, patients were also assessed using the
Hamilton Depression Rating Scale, Symptom Cheecklist-90 (SCL-90) and Short
Form-36 (SF36) physical component summary score as the main outcome measure.
Partial correlation was used to compare changes in SF36 score and changes in
psychological scores while controlling for possible confounders, treatment group
and baseline scores. Multiple regression analysis was used to examine whether
changes in psychological scores, changes in pain and a history of abuse could
account for most of the variance of change in SF36 physical component score.
RESULTS: Of 257 patients with severe IBS, 107 (42%) had a depressive, panic or
generalized anxiety disorder at trial entry. There were moderate but significant
correlations (0.21-0.47) between change in the psychological scores and the
change in SF36 physical component scores. The correlation coefficients were
similar in the groups with and without psychiatric disorder. The superiority of
psychotherapy and antidepressant groups over treatment as usual was similar in
those with and without psychiatric disorder. Multiple regression found
significant independent effects of change in depression, anxiety, somatization
and abdominal pain but there was still variance explained by treatment group.
CONCLUSIONS: In severe IBS improvement in health-related quality of life
following psychotherapy or antidepressants is correlated with, but not explained
fully by reduction of psychological scores. A more complete understanding of how
these treatments help patients with medically unexplained symptoms will enable
us to refine them further.
-----
Aliment Pharmacol Ther. 2005 Sep 1;22(5):373-80.
Effect of tegaserod on work and daily activity in irritable bowel
syndrome with constipation.
Reilly MC, Barghout V, McBurney CR, Niecko TE.
Margaret Reilly Associates, Inc., New York, NY, USA. mreilly@reillyassociates.net
BACKGROUND: Tegaserod is a promotility agent with proven efficacy and safety in
patients with irritable bowel syndrome with constipation. AIM: To assess
tegaserod's effect on work productivity and daily activity. METHODS: Women,
18-65 years old and meeting Rome II criteria for irritable bowel syndrome with
constipation, were randomized to a double-blind, placebo-controlled, multicentre
study of tegaserod 6 mg b.d. or placebo. Productivity loss and daily activity
impairment because of irritable bowel syndrome were measured with the Work
Productivity and Activity Impairment questionnaire for irritable bowel syndrome,
modified to exclude diarrhoea as a symptom. Assessments were made at baseline,
weeks 2 and 4. RESULTS: A total of 2660 women were randomized and, of these,
1675 [tegaserod (n = 1363), placebo (n = 312)] were employed and completed Work
Productivity and Activity Impairment for irritable bowel syndrome
questionnaires. Compared with placebo, tegaserod significantly reduced work and
daily activity impairment at weeks 2 and 4. Tegaserod reduced absenteeism by
2.6% (P = 0.004), presenteeism by 5.4% (P < 0.0001), overall work productivity
loss by 6.3% (P < 0.0001), and activity impairment by 5.8% (P < 0.0001) at week
4 (vs. baseline). Assuming a 40-h workweek, tegaserod reduced work productivity
loss by 2.5 h/week. CONCLUSIONS: Tegaserod significantly reduced work
productivity loss and daily activity impairment at 2 weeks, and this benefit was
maintained at 4 weeks.
-----
Gut. 2005 Sep 22; [Epub ahead of print]
Acupuncture treatment in irritable bowel syndrome.
Schneider A, Enck P, Streitberger K, Weiland C, Bagheri S, Witte S, Friederich
HC, Herzog W, Zipfel S.
University of Heidelberg, Department of General Practice and Health Services
Research, Germany.
BACKGROUND AND AIMS: Despite occasional positive reports on the efficacy of
acupuncture on functions of the gastrointestinal tract, there is no conclusive
evidence that acupuncture (AC) is effective in the treatment of irritable bowel
syndrome (IBS). PATIENTS AND METHODS: 43 patients with IBS according to Rome II
criteria were randomly assigned to receive either acupuncture (n=22) or sham
acupuncture (n=21) (SAC) using the so-called "Streitberger needle". Treatment
duration was 10 sessions with an average of 2 acupuncture sessions per week, and
primary endpoint was improvement of quality of life (QOL) using the Functional
Digestive Diseases Quality of Life Questionnaire (FDDQL) and a general Quality
of Life Questionnaire (SF-36), compared to baseline assessment. QOL measurement
was repeated three months after treatment. RESULTS: Both the AC as well as the
SAC group improved significantly in global QOL by the FDDQL at the end of
treatment (p=0.022), with no differences between both groups. The SF36 was
insensitive to these changes (except for pain). This effect was partially
reversed three months later. Post-hoc comparison of responders and
non-responders in both groups combined revealed a significant prediction of the
placebo response by two subscales of the FDDQL (sleep, coping) (F=6.746,
p=0.003) in a stepwise regression model. CONCLUSIONS: Acupuncture in IBS is
primarily a placebo response. Based on the small differences found between AC
and SAC, a study including 566 patients would be necessary to prove efficacy of
AC over SAC. The placebo response may be predicted by high coping capacity and
low sleep quality in individual patients.
-----
Aliment Pharmacol Ther. 2005 Sep 1;22(5):387-94.
A probiotic mixture alleviates symptoms in irritable bowel
syndrome patients: a controlled 6-month intervention.
Kajander K, Hatakka K, Poussa T, Farkkila M, Korpela R.
Valio Ltd, Research Centre, Helsinki, Finland.
BACKGROUND: Irritable bowel syndrome is a gastrointestinal disorder of unknown
aetiology. The effect of probiotics in this syndrome remains unclear. AIM: To
investigate whether a probiotic mixture containing Lactobacillus rhamnosus GG,
L. rhamnosus LC705, Bifidobacterium breve Bb99 and Propionibacterium
freudenreichii ssp. shermanii JS is effective in alleviating irritable bowel
syndrome symptoms. METHODS: A total of 103 patients fulfilling the Rome I or II
criteria took part in this 6-month, randomized, double-blind placebo-controlled
trial. The patients received a probiotic capsule or a placebo capsule daily.
Gastrointestinal symptoms and bowel habits were recorded. RESULTS: At the end
the total symptom score (abdominal pain + distension + flatulence + borborygmi)
was 7.7 (95% CI: -13.9 to -1.6) points lower in the probiotic group (P = 0.015).
This represents a median reduction of 42% in the symptom score of the probiotic
group compared with 6% in the placebo group. In individual symptoms, borborygmi
was milder in the probiotic group (P = 0.008), and for the rest of the symptoms
there was a non-significant trend. CONCLUSIONS: The results indicate that this
probiotic mixture is effective in alleviating irritable bowel syndrome symptoms.
Considering the high prevalence of irritable bowel syndrome and the lack of
effective therapies, even a slight reduction in symptoms could have positive
public health consequences.
-----
Scand J Gastroenterol. 2005 Aug;40(8):936-43.
Herbal medicine with curcuma and fumitory in the treatment of
irritable bowel syndrome: a randomized, placebo-controlled, double-blind
clinical trial.
Brinkhaus B, Hentschel C, Von Keudell C, Schindler G, Lindner M, Stutzer H,
Kohnen R, Willich SN, Lehmacher W, Hahn EG.
Institute of Social Medicine, Epidemiology, and Health Economics, Charite
University Medical Center, Luisenstr. 57, DE-10098 Berlin, Germany.
benno.brinkhaus@charite.de
OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional disorder for
which there is no reliable medical treatment. The aim of this study was to
determine the efficacy of two herbal remedies used in the treatment of IBS.
MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled trial,
IBS patients were randomly assigned to one of three treatment groups: 1) Curcuma
xanthorriza 60 mg daily (curcuma group) (n=24), 2) Fumaria officinalis 1500 mg
daily (fumitory group) (n=24) and 3) placebo (n=58). The study treatment was
applied three times a day for 18 weeks. The main outcome parameters were changes
in global patient ratings of IBS-related pain and distension on a visual
analogue scale (0-50 mm) between baseline and at the end of treatment.
Additional outcome parameters included global assessments of changes in IBS
symptoms and psychosocial stress caused by IBS. RESULTS: A total of 106 patients
(mean age 48+/-12 years, 63% F) were included in the intention-to-treat group.
IBS-related pain decreased by -0.9+/-11.5 (mm+/-SD) in the fumitory group,
-0.3+/-9.9 in the placebo group and increased by 2.0+/-9.5 in the curcuma group
(p=0.81). IBS-related distension decreased by -1.4+/-12.5 in the curcuma group,
-2.1+/-9.2 in the placebo group and increased by 0.3+/-9.3 in the fumitory group
(p=0.48). Additionally, the global assessment of changes in IBS symptoms and
psychological stress due to IBS did not differ significantly among the three
treatment groups. CONCLUSIONS: Neither fumitory nor curcuma showed any
therapeutic benefit over placebo in patients with IBS. Therefore, the use of
these herbs for the treatment of IBS cannot be recommended.
-----
J Pediatr. 2005 Aug;147(2):197-201.
The use of Lactobacillus GG in irritable bowel syndrome in
children: a double-blind randomized control trial.
Bausserman M, Michail S.
Department of Pediatrics, Wright State University School of Medicine and The
Children's Medical Center, Dayton, Ohio 45404, USA.
OBJECTIVE: To determine whether oral administration of the probiotic
Lactobacillus GG under randomized, double-blinded, placebo-controlled conditions
would improve symptoms of irritable bowel syndrome (IBS) in children. STUDY
DESIGN: Fifty children fulfilling the Rome II criteria for IBS were given
Lactobacillus GG or placebo for 6 weeks. Response to therapy was recorded and
collected on a weekly basis using the Gastrointestinal Symptom Rating Scale (GSRS).
RESULTS: Lactobacillus GG was not superior to placebo in relieving abdominal
pain (40.0% response rate in the placebo group vs 44.0% in the Lactobacillus GG
group; P=.774). There was no difference in the other gastrointestinal symptoms,
except for a lower incidence of perceived abdominal distention (P=.02 favoring
Lactobacillus GG). CONCLUSIONS: Lactobacillus GG was not superior to placebo in
the treatment of abdominal pain in children with IBS but may help relieve such
symptoms as perceived abdominal distention.
-----
Prim Care Companion J Clin Psychiatry. 2005;7(4):162-166.
Open-Label Treatment With Citalopram in Patients With Irritable
Bowel Syndrome: A Pilot Study.
Masand PS, Gupta S, Schwartz TL, Virk S, Hameed A, Kaplan DS.
Department of Psychiatry, Duke University Medical Center, Durham, N.C. ; the
Department of Psychiatry, Olean General Hospital, Olean, N.Y. ; the Department
of Psychiatry, State University of New York Upstate Medical University, Syracuse
; and Syracuse Gastroenterological Associates, Syracuse, N.Y.
Background: This open-label pilot study investigated whether the selective
serotonin reuptake inhibitor (SSRI) citalopram improves symptoms of irritable
bowel syndrome (IBS), a functional gastrointestinal disorder with frequent
psychiatric comorbidity.Method: Fifteen patients meeting Rome I criteria for IBS
were administered open-label citalopram (20-40 mg/day) for 12 weeks. The study
was conducted from October 2000 to August 2001.Results: Twelve (80%) of the 15
subjects reported a >/= 50% decrease in the presence of abdominal pain, 10 (67%)
reported a >/= 50% reduction in the severity of the symptom, and 12 (80%)
reported a >/= 50% reduction in the frequency of the symptom. Approximately one
half of the patients met criteria for remission (>/= 70% improvement) of
abdominal pain.Conclusion: Results of this pilot study suggest that large
controlled trials are needed to further evaluate the efficacy of SSRIs such as
citalopram for the treatment of IBS.
-----
Phytomedicine. 2005 Aug;12(8):601-6.
Peppermint oil in irritable bowel syndrome.
Grigoleit HG, Grigoleit P.
Dr.Grigoleit@t-online.de
In a literature search 16 clinical trials investigating 180-200 mg
enteric-coated peppermint oil (PO) in irritable bowel syndrome (IBS) or
recurrent abdominal pain in children (1 study) with 651 patients enrolled were
identified. Nine out of 16 studies were randomized double blind cross over
trials with (n = 5) or without (n = 4) run in and/or wash out periods, five had
a randomized double blind parallel group design and two were open labeled
studies. Placebo served in 12 and anticholinergics in three studies as
comparator. Eight out of 12 placebo controlled studies show statistically
significant effects in favor of PO. Average response rates in terms of "overall
success" are 58% (range 39-79%) for PO and 29% (range 10-52%) for placebo. The
three studies versus smooth muscle relaxants did not show differences between
treatments hinting for equivalence of treatments. Adverse events reported were
generally mild and transient, but very specific. PO caused the typical GI
effects like heartburn and anal/perianal burning or discomfort sensations,
whereas the anticholinergics caused dry mouth and blurred vision.
Anticholinergics and 5HT3/4-ant/agonists do not offer superior improvement
rates, placebo responses cover the range as in PO trials. Taking into account
the currently available drug treatments for IBS PO (1-2 capsules t.i.d. over 24
weeks) may be the drug of first choice in IBS patients with non-serious
constipation or diarrhea to alleviate general symptoms and to improve quality of
life.
-----
BMJ. 2005 Aug 20;331(7514):435. Epub 2005 Aug 10.
Cognitive behaviour therapy in addition to antispasmodic
treatment for irritable bowel syndrome in primary care: randomised
controlled trial.
Kennedy T, Jones R, Darnley S, Seed P, Wessely S, Chalder T.
Department of General Practice and Primary Care, Guy's, King's, and St Thomas'
School of Medicine, King's College, London SE11 6SP.
OBJECTIVE: To assess the efficacy of cognitive behaviour therapy delivered in
primary care for treating irritable bowel syndrome. DESIGN: Randomised
controlled trial. SETTING: 10 general practices in London. PARTICIPANTS: 149
patients with moderate or severe irritable bowel syndrome resistant to the
antispasmodic mebeverine. INTERVENTIONS: Cognitive behaviour therapy delivered
by trained primary care nurses plus 270 mg mebeverine taken thrice daily
compared with mebeverine treatment alone. MAIN OUTCOME MEASURES: Primary
measures were patients' scores on the irritable bowel syndrome symptom severity
scale. Secondary measures were scores on the work and social adjustment scale
and the hospital anxiety and depression scale. RESULTS: Of 334 referred
patients, 72 were randomised to mebeverine plus cognitive behaviour therapy and
77 to mebeverine alone. Cognitive behaviour therapy had considerable initial
benefit on symptom severity compared with mebeverine alone, with a mean
reduction in score of 68 points (95% confidence interval 103 to 33), with the
benefit persisting at three months and six months after therapy (mean reductions
71 points (109 to 32) and 11 points (20 to 3)) but not later. Cognitive
behaviour therapy also showed significant benefit on the work and social
adjustment scale that was still present 12 months after therapy (mean reduction
2.8 points (5.2 to 0.4)), but had an inconsistent effect on the hospital anxiety
and depression scale. CONCLUSION: Cognitive behaviour therapy delivered by
primary care nurses offered additional benefit over mebeverine alone up to six
months, although the effect had waned by 12 months. Such therapy may be useful
for certain patients with irritable bowel syndrome in primary care.
-----
Gastroenterol Clin North Am. 2005 Jun;34(2):337-54.
Potential future therapies for irritable bowel syndrome: will
disease modifying therapy as opposed to symptomatic
control become a reality?
Spiller RC.
Wolfson Digestive Diseases Centre, University Hospital, C Floor South Bank,
Nottingham NG7 2UH, United Kingdom. emma.bradley@nottingham.ac.uk
Irritable bowel syndrome can remit spontaneously, implying cure is possible.
Predictors of good prognosis include a short history, acute onset(possibly
postinfective origin), absence of psychological disorders, and resolution of
chronic life stressors. Possible-disease modifying treatments with long-lasting
effects include diet and anti-inflammatory and psychological treatments. Dietary
modifications, which often involve excluding dairy and wheat products, are
successful in some patients. Anti-inflammatory treatments have been subjected to
one RCT in postinfective IBS without benefit. Probiotics may have benefit in
altering bacterial flora and as anti-inflammatory agents, but further trials are
needed before they can be recommended. Psychological treatments may produce
long-lasting responses. Relaxation therapy appears to have a nonspecific
benefit. Psychotherapy has been shown to have long-term benefit and is
particularly acceptable to, and effective for, those with overt psychological
distress. Hypnotherapy has been shown to be effective in randomized placebo
controlled trials and has a sustained effect.
-----
Gastroenterol Clin North Am. 2005 Jun;34(2):319-35, viii.
Efficacy of current drug therapies in irritable bowel syndrome:
what works and does not work.
Schoenfeld P.
Division of Gastroenterology, University of Michigan School of Medicine, VAMC
111-D, 2215 Fuller Road, Ann Arbor, MI 48105, USA. pschoenf@umich.edu
Based on current evidence, bulking agents are not more effective than placebo at
improving global irritable bowel syndrome (IBS)symptoms, although they may
increase stool frequency in large doses. Tricyclic antidepressants are more
effective than placebo for patients with diarrhea-predominant IBS. Imodium is
more effective than placebo at improving stool consistency and decreasing stool
frequency in patients with IBS, and it may be an important component for
treating diarrhea-predominant IBS. Antispasmodics agents available in the United
States are not more effective than placebo for treating IBS, although the
studies are small and poorly designed. There are no randomized controlled trials
examining the efficacy of laxatives for managing IBS. Tegaserod is more
effective than placebo at improving global IBS symptoms in women with
nondiarrhea-predominant IBS. Alosetron is more effective than placebo in women
with diarrhea-predominant IBS, although its use should be limited to patients
who have failed conventional therapy because of its adverse event profile.
-----
Dig Dis Sci. 2005 Jun;50(6):1107-12.
Treatment effects of partially hydrolyzed guar gum on symptoms
and quality of life of patients with irritable bowel syndrome. A multicenter
randomized open trial.
Parisi G, Bottona E, Carrara M, Cardin F, Faedo A, Goldin D, Marino M, Pantalena
M, Tafner G, Verdianelli G, Zilli M, Leandro G.
Servizio di Gastroenterologia, Casa di Cura Abano Terme, ULSS 16, Padova, Italy.
The effects of partially hydrolyzed guar gum (PHGG) were compared in patients
with irritable bowel syndrome, at 10 g/day (N = 40) and 5 g/day (N = 46) for 12
weeks. Gastrointestinal symptoms (GSRS), quality of life (SF-36), and
psychological symptoms (HADS) were evaluated at baseline, during treatment
(months 1 and 3), and at follow-up (month 6). In both groups symptoms and
quality of life improved significantly after the first month of administration
until follow-up compared to those at baseline. However, the improvement was
significantly reduced at follow-up compared to the end of treatment. PHGG was
effective for improving somatic (gastrointestinal symptoms) and psychological
(quality of life and psychological distress) symptoms over the short term. Since
the improvement tended to decrease after the end of the treatment period,
further studies should evaluate the benefits of PHGG at a maintenance dosage.
-----
Curr Treat Options Gastroenterol. 2005 Jun;8(3):211-221.
Managing Functional Disturbances in Patients with Inflammatory
Bowel Disease.
Ginsburg PM, Bayless TM.
The Johns Hopkins Hospital, 461 Blalock Building, 600 North Wolfe Street,
Baltimore, MD 21287, USA. tbayless@jhmi.edu.
Functional disturbances occur in approximately 10% to 15% of the general
population and in a similar percentage of patients with inflammatory bowel
disease (IBD). Because overlapping irritable bowel syndrome (IBS) is so common,
one of the most important interventions a clinician can make is recognizing its
existence. This requires a thorough understanding of underlying pathophysiologic
processes. Differentiating among the causes of symptoms is especially
significant in a minority of patients mislabeled as having 'refractory IBD.'
Escalating therapy directed at disease activity may have no effect on functional
symptoms other than to reinforce their presence. Treatment of IBS in patients
with IBD is similar to that of the general population. The cornerstone of
treatment is establishing a constructive doctor-patient relationship. Initial
therapy usually involves a conservative approach that includes patient education
and diet and lifestyle modifications. Pharmacologic treatment is individualized
and generally directed at the predominant symptoms. Options may broadly include
antispasmodics, antidiarrheals, and antidepressants, either alone or in
combination. Psychosocial therapies have shown to be beneficial in selected
individuals.
-----
Z Gastroenterol. 2005 May;43(5):467-71.
[Probiotics as therapeutic agents in irritable bowel syndrome.]
[Article in German]
Krammer HJ, Schlieger F, Harder H, Franke A, Singer MV.
II. Medizinische Universitatsklinik (Gastroenterologie, Hepatologie,
Infektionskrankheiten), Universitatsklinikum Mannheim. h.krammer@med.ma.uni-heidelberg.de
Probiotics are defined as living micro-organisms which, when administered in
large amounts, confer a health benefit on the host. The use of probiotics in the
therapy of infectious bowel diseases as well as maintaining remission of
ulcerative colitis and in pouchitis is evidence-based. Also, in several studies
proof could be supplied that specific probiotics relieve the symptoms and the
course of irritable bowel syndrome. Some trials showed a significant improvement
of irritable bowel syndrome-related constipation via Lactobacillus casei Shirota
and E. coli Nissle 1917. Lactobacillus plantarum has been proven effective in
reducing pain and abdominal bloating. However, in most of the studies rather
small numbers of patients were examined. Furthermore, these studies do not
always closely follow scientific standards (randomised, double-blind,
placebo-controlled). Therefore, confirmatory studies are necessary to examine
the effect of probiotics in irritable bowel syndrome.
-----
Expert Rev Anti Infect Ther. 2005 Apr;3(2):201-11.
Rifaximin: a nonabsorbable rifamycin antibiotic for use in
nonsystemic gastrointestinal infections.
Gerard L, Garey KW, DuPont HL.
University of Houston College of Pharmacy, TX 77030, USA.
Rifaximin is a poorly water-soluble and minimally absorbed (<0.4%) rifamycin
with in vitro activity against enteric Gram-negative bacteria including enteric
pathogens. Fecal levels of the drug after 3 days' oral therapy exceed 8000
microg/g. Rifaximin is effective in the treatment and prevention of travelers'
diarrhea due to Escherichia coli-predominant bacterial pathogens. It shows lower
activity against dysenteric forms of bacterial diarrhea. The drug may be useful
in other enteric infectious diseases, including Clostridium difficile colitis,
pediatric bacterial diarrhea and Helicobacter pylori gastritis and chronic
gastrointestinal disorders including hepatic encephalopathy, small bowel
bacterial overgrowth, inflammatory-bowel disease, irritable-bowel syndrome and
pouchitis. Importantly, rifaximin does not appear to lead to bacterial
resistance. Rifaximin has an excellent safety profile and adverse drug reactions
have been comparable to those associated with the placebo control agent.
-----
Cochrane Database Syst Rev. 2005 Apr 18;(2):CD003460.
Bulking agents, antispasmodic and antidepressant medication for
the treatment of irritable bowel syndrome.
Quartero AO, Meineche-Schmidt V, Muris J, Rubin G, de Wit N.
Julius Center for General Practice and Patient Oriented Research, University
Medical Center Utrecht, P.O. Box 85060, 3508 AB Utrecht, Netherlands.
a.o.quartero@med.uu.nl
BACKGROUND: Irritable bowel syndrome (IBS) is a common health problem, often
presenting in primary care as well as in internal medicine and gastroenterology
outpatient clinics. Therapeutic options are dominated by drug therapies but
there is uncertainty about their effectiveness. OBJECTIVES: The primary
objective of this review was to evaluate the efficacy of bulking agents,
antispasmodic and antidepressant medication for the treatment of IBS. SEARCH
STRATEGY: A computer assisted search of MEDLINE, EMBASE, PsychInfo and the
Cochrane Library was performed for the years 1966-2001; local and national
databases were searched in 10 European countries. SELECTION CRITERIA: Randomised
trials comparing bulking agents, antispasmodic or antidepressant medications
with a placebo, in IBS patients over 12 years of age. Only studies published as
a full paper were included. No language criterion was applied. DATA COLLECTION
AND ANALYSIS: The search identified 687 studies, 66 of which fulfilled all
eligibility criteria. After removal of cross-over studies that did not report
separately on the first phase, data from 40 studies remained for analysis.
Relative risk (RR), risk difference (RD) and standardized mean difference (SMD)
along with 95% confidence intervals were calculated for all subgroups. The
number needed to treat (NNT) was also calculated where appropriate. MAIN
RESULTS: Forty-one study reports from 40 studies, comprising 78 comparisons,
were analysed. These included 11 reports on bulking agents, 6 on
antidepressants, and 24 on spasmolytics.BULKING AGENTS: Three studies comprising
159 patients reported a dichotomous outcome for relief of abdominal pain. The
pooled RR using a random effects model was 1.22 (95% CI 0.86 - 1.73). Three
studies comprising 128 patients reported a continuous outcome for relief of
abdominal pain. Using the random effects model, the SMD was 0.68 (95% CI -0.86 -
2.33). Nine studies comprising 482 patients reported a dichotomous outcome for
global assessment of improvement. The pooled RR was 1.09 (95% CI 0.78 - 1.50).
Five studies comprising 253 patients reported a dichotomous outcome for
improvement of symptom score. The pooled RR using a random effects model was
0.93 (95% CI 0.56 - 1.54). Two studies comprising 70 patients reported a
continuous outcome for improvement of symptom score; the SMD using a fixed
effects model was -0.44 (95% CI -1.20 - 0.31). SPASMOLYTIC AGENTS: Eleven
studies comprising 1260 patients reported a dichotomous outcome for relief of
abdominal pain. The pooled RR using a random effects model was 1.34 (95% CI 1.13
- 1.59; RD=0.17, 95% CI 0.06 -0.28; NNT=6, 95% CI 4 - 15). Seven studies
comprising 467 patients reported a continuous outcome for relief of abdominal
pain. Using a fixed effects model the pooled SMD was -0.65 (95% CI -0.94 to
-0.35). Sixteen studies comprising 1236 patients reported a dichotomous outcome
for global assessment of improvement. The pooled RR using a random effects model
was 1.42 (95% CI 1.17 - 1.72; RD=0.20, 95% CI 0.09 -0.30; NNT=5, 95% CI 3 - 11).
One study comprising 34 patients reported a dichotomous variable for improvement
of symptom score. The RR was 1.33 (95% CI 0.96 - 1.85). Three studies reported a
continuous outcome for improvement of symptom score; two studies comprising 66
patients could be pooled. Using a fixed effects model, the SMD was -0.37 (95% CI
-0.85 - 0.12). ANTIDEPRESSANTS: Two studies comprising 81 patients reported a
dichotomous outcome for relief of abdominal pain. Using the random effects
model, the pooled RR was 0.83 (95% CI 0.33 - 2.12). Two studies comprising 101
patients reported a continuous outcome for relief of abdominal pain. The SMD
using a random effects model was -0.53 (95% CI -2.29 - 1.23). Four studies
comprising 241 patients reported a dichotomous variable for global assessment of
improvement. The pooled RR was 1.16 (95% CI 0.78 - 1.73). AUTHORS' CONCLUSIONS:
The evidence for efficacy of drug therapies for IBS is weak. Although there is
evidence of benefit for antispasmodic drugs for abdominal pain and global
assessment of symptoms; it is unclear whether anti-spasmodic subgroups are
individually effective. There is no clear evidence of benefit for
antidepressants or bulking agents. The physician should be aware that global
assessment is a construct containing various dimensions. For each individual,
these will have a different weighting and treatment should be aimed at the most
debilitating symptom. Stool problems are by definition part of the IBS symptom
complex. Bulking agents may improve constipation and can be used empirically,
but should be evaluated at an early stage for individual benefit. Future
research should pay attention to study methodology and the use of valid outcome
measures.
-----
J Clin Gastroenterol. 2005 Apr;39(4):S247-50.
Psychotherapeutics and serotonin agonists and antagonists.
Mertz H.
>From the Department of Medicine, Vanderbilt University, Nashville, TN.
Treatment of irritable bowel syndrome (IBS) remains challenging for patients and
practitioners. Current therapeutic choices include antidepressants and
psychotherapy, which are thought to target central nervous system triggers of
symptoms. Data supporting these treatments are reviewed. Therapeutic agents
targeted at receptors in the enteric nervous system have recently been developed
to act locally in the gut. Alosetron, an antagonist for serotonin-3 receptors,
reduces intestinal motility, secretion, and possibly sensitivity. It is
effective for diarrhea predominant IBS, although there are some potentially
serious side effects. Tegaserod, a serotonin-4 receptor agonist, is a prokinetic
agent that speeds small bowel transit and right colon transit in IBS, reducing
symptoms of constipation, pain, and bloating. IBS symptoms are improved with
integration of old and new therapies, combined with reassurance, education, and
lifestyle adjustments.
-----
J Clin Gastroenterol. 2005 Apr;39(4):S251-6.
What does the future hold for irritable bowel syndrome and the
functional gastrointestinal disorders?
Drossman DA.
>From the Department of Medicine and Psychiatry and UNC Center for Functional GI
and Motility Disorders, University of North Carolina at Chapel Hill, Chapel
Hill, NC.
Our understanding of irritable bowel syndrome and the functional GI disorders
has grown considerably over the last 15 years. In part this relates changes in
their classification and definition from being due solely to motility
disturbances, to being symptom based (eg, Rome criteria). This opened the door
to the study of many other factors that contribute to the clinical expression of
these disorders, including visceral hypersensitivity, sensitization, altered
mucosal immunity, and dysfunction in brain-gut regulatory processes. New
knowledge has been gained in areas of genetics, central nervous system and
enteric nervous system neurotransmitters of motility, sensitivity and secretion,
the effect of altered mucosal inflammation on cytokine and paracrine activation,
and neural sensitization, postinfectious disorders, the influence of psychologic
stress on gut functioning via alterations in regulatory pathways (eg,
hypothalamic-pituitary adrenal axis, or pain regulatory system like the
cingulate cortex), improved accuracy of diagnosis using Rome II criteria plus
"red flags" the institution of behavioral treatments, and the use of new
pharmacologic treatments both at the gut and brain level. Future research will
improve upon this new knowledge via basic and translational studies of
neuropeptide signaling with new neurotransmitters, new knowledge on the
mechanisms for central nervous system-enteric nervous system communication and
dysfunction, and more advanced clinical research on education, communication
skills and their effects on outcome, genetics, pharmacogenetics and genetic
epidemiology, better understanding as to how certain psychosocial domains (eg,
catastrophizing, abuse) affect symptom behavior and outcome, newer pharmacologic
treatments, and the use of combined pharmacologic and behavioral treatment
packages. I am pleased to have the opportunity to provide a personal perspective
on what the future will be for irritable bowel syndrome and the other functional
GI disorders. Having been involved in this field for almost 30 years, I have
been fortunate to witness tremendous changes. The focus of this presentation is
to address the advances that have recently occurred that set the stage for
proposing future research to help move the field along and ultimately to help
our patients.
-----
J Clin Gastroenterol. 2005 Apr;39(4):S243-6.
Use of diet and probiotic therapy in the irritable bowel
syndrome: analysis of the literature.
Floch MH.
>From the Section of Gastroenterology, Yale University School of Medicine,
Norwalk Hospital, Norwalk, CT.
GOAL:: The goal of this report is to review the use of dietary intake and
probiotics in patients with irritable bowel syndrome (IBS) in published reports.
BACKGROUND:: Dietary factors can be important in inducing symptoms that occur in
patients with the IBS. Dietary intolerances, dietary allergies, specific food
metabolites, and regular diet contents all may act as triggers and aggravate the
symptoms of IBS; but when any of these mechanisms can be proven to cause the
symptoms, then their elimination results in the resolution of that patient's
IBS. METHODS:: Our previous review was updated. In addition, a careful Medline
search was made for the years from 1975 to 2004 to evaluate human research
reports on diet and probiotics in the IBS. Forty-six manuscripts were reviewed
on diet and six were available on probiotic use in IBS. The most common dietary
factor evaluated in the literature was bran, and the most common probiotic used
was Lactobacillus plantarum. CONCLUSIONS:: Although investigations have shown
that bran may be helpful in some patients, a complete review of the literature
does not reveal conclusive evidence that diet therapy is effective in IBS. From
the limited reports on probiotics, there appears to be a trend to decreasing
symptoms. It is clear that much more prospective research is needed to study
both dietary factors and probiotics in these areas.
-----
Eur J Gastroenterol Hepatol. 2005 Apr;17(4):421-427.
Tegaserod is safe, well tolerated and effective in the treatment
of patients with non-diarrhoea irritable bowel syndrome.
Fried M, Beglinger C, Bobalj NG, Minor N, Coello N, Michetti P; on behalf of the
TegaSwiss Study Group.
aDepartment of Gastroenterology, University Hospital Zurich, Switzerland
bDepartment of Gastroenterology, University Hospital Basel, Switzerland
cNovartis Pharma Switzerland, Bern, Switzerland dPharma Focus Consultants AG,
Volketswil, Switzerland eBiometrical Practice BIOP AG, Basel, Switzerland
fDepartment of Gastroenterology, University Hospital, Lausanne, Switzerland.
OBJECTIVE: To evaluate the safety/tolerability and efficacy of tegaserod, a
5-HT4 receptor partial agonist, in the treatment of patients with non-diarrhoea
irritable bowel syndrome (non-D-IBS) in Switzerland. METHODS: This was an
8-week, open-label, prospective, multicentre study. Patients (>/=18 years old)
met the Rome II diagnostic criteria for IBS, excluding those with diarrhoea for
>/=14 days in the previous 3 months. Details of IBS symptoms experienced in the
preceding week were recorded at visit 1 (day 1). Eligible patients received 6 mg
tegaserod twice daily for 8 weeks. Adverse events (AEs) and serious AEs were
recorded, along with detailed assessment of diarrhoeal episodes. Efficacy
assessments included the overall number and percentage of responders after 8
weeks' treatment. RESULTS: A total of 850 patients (72% women; mean age, 51.4
years) were enrolled, and 843 received at least one dose of tegaserod. AEs were
reported in 38% of patients, of which 13% were drug-related. Diarrhoea occurred
early during treatment (13% in the first week, 7% thereafter), was mild to
moderate in severity, was transient and was resolved with continued treatment.
In total, 208 patients left the study early, primarily due to AEs. Diarrhoea
accounted for 68 of these discontinuations. Nine serious AEs were reported but
these were not related to tegaserod treatment. Sixty-six percent of patients
responded to tegaserod on the Subject's Global Assessment of relief after 8
weeks. Benefits were also seen across individual IBS symptoms. CONCLUSION:
Tegaserod (6 mg twice daily) appears to be safe, well-tolerated and effective in
the treatment of non-D-IBS over 8 weeks.
-----
Br Med Bull. 2005 Mar 14;72:15-29. Print 2005.
Irritable bowel syndrome.
Spiller RC.
Wolfson Digestive Diseases Centre, University Hospital, Nottingham, NG7 2UH, UK.
robin.spiller@nottingham.ac.uk.
Irritable bowel syndrome (IBS) is one of the most common 'functional'
gastrointestinal disorders accounting for 3% of all primary care consultations,
with a strong female predominance. Although most of the literature comes from
Western industrialized societies, when it has been looked for, this disorder
appears to be equally common in the Third World. It is characterized by chronic
abdominal pain or discomfort associated with disordered bowel habit and visceral
hypersensitivity. Anxiety and somatization are more common in IBS than in the
general population and may encourage consultation; however, they correlate
poorly with symptoms. Bacterial gastroenteritis may be followed by the
development of IBS in 5-10% of patients, depending on the severity of initial
illness and prior anxiety or depression. The Rome criteria allow reliable
diagnosis provided that there are no 'alarm' features which mandate further
investigation. Microscopic colitis and bile salt malabsorption can easily be
mistaken for IBS, as can chronic infestations or infections which should be
considered, while recognizing that these are extremely uncommon in westernized
societies. Some patients respond to exclusion diets as lactose and wheat
intolerance are common. Others with prominent anxiety and/or depression respond
to psychotherapy or antidepressants. Diarrhoeal symptoms respond to loperamide
and 5HT3 receptor antagonists, while constipation responds to 5HT4 agonists.
Antispasmodics may have limited benefit in treating pain. Low-dose tricyclic
antidepressants are also helpful in alleviating pain and anxiety, even in those
without obvious psychiatric disorders. If diagnostic criteria are met, then once
diagnosed, new diagnoses rarely appear.
-----
Expert Opin Investig Drugs. 2005 Feb;14(2):185-93.
Cilansetron: a new serotonergic agent for the irritable bowel
syndrome with diarrhoea.
Chey WD, Cash BD.
University of Michigan, Division of Gastroenterology, Ann Arbor, MI, USA. wchey@umich.edu.
Cilansetron is a novel serotonin type-3 (5-hydroxytryptamine; 5-HT) receptor
subtype 3 (5-HT(3)) receptor antagonist currently being evaluated for the
treatment of female and male patients with irritable bowel syndrome with
diarrhoea predominance (IBS-D). 5-HT(3) receptor antagonists such as cilansetron
have been shown to affect gastrointestinal motility. Whether cilansetron affects
visceral sensation independent of effects on visceral compliance remains
controversial. Results from two large, randomised, double-blind,
placebo-controlled, parallel-group Phase III clinical trials of cilansetron in
patients with IBS-D have recently been presented in abstract form. These studies
found that cilansetron was more effective than placebo at improving overall, as
well as individual symptoms, including abdominal pain and diarrhoea in female
and male IBS-D patients. The most commonly reported side effect with cilansetron
has been constipation and, in general, the drug has been well tolerated in
clinical trials. Although rare, the most concerning side effect observed with
cilansetron has been suspected ischaemic colitis. The event rate for suspected
ischaemic colitis associated with cilansetron from clinical trials is 3.77 per
1000 person years of exposure. This rate appears to be greater than that
expected in the IBS population and similar to that observed with alosetron,
another 5--HT(3) receptor antagonist. All of the cases of suspected ischaemic
colitis reported with cilansetron have resolved without serious sequelae. How
issues surrounding the safety of cilansetron will affect the approval process in
various countries remains to be determined. However, the risk-benefit of
cilansetron is likely to be most favourable in patients with IBS-D who have
failed to respond to conventional medical therapies. A detailed risk management
plan and post-marketing surveillance programme will be required should this drug
become available for the treatment of patients with IBS-D.
-----
Dtsch Med Wochenschr. 2005 Feb 25;130(8):399-401.
[Irritable bowel syndrome]
[Article in German]
Adam B, Liebregts T, Holtmann G.
Royal Adelaide Hospital, Department of Gastroenterology, Hepatology and General
Medicine, University of Adelaide.
Patients with irritable bowel syndrome (IBS) are highly prevalent among subjects
seeking medical attention at the general practitioner or specialist level. While
IBS lacks any disease associated excess mortality, this disorders is relevant to
the affected subjects due to the considerable burden with regard to the symptoms
and an impaired quality of life. Furthermore, this disease has a substantial
impact on society due to the economical consequences. In recent years
substantial progress has been achieved regarding our pathophysiological
understanding. However, as usual, there has been a substantial delay between the
discovery of disease mechanisms and its translation into improved patient care.
For diagnosing IBS standardized criteria have been established (i. e. Rome II-
or the DGVS-criteria). Regarding treatment, life style advice such as avoidance
of specific nutrients that precipitate or aggravate or the "little
psychotherapy" (addressing patients concerns and anxiety regarding the symptoms)
are considered essential. However, the overall response rate is disappointing.
Evidence-based pharmacological interventions include herbal preparations,
spasmolytics, low dose tricyclic antidepressants and 5-HT-3-receptor antagonists
and 5-HT-4-receptor agonists. At present no cure for patients with IBS exists.
Thus, all currently available treatments target palliation of symptoms. This,
however, may change in the future.
-----
Aliment Pharmacol Ther. 2005 Feb 15;21(4):435-44.
Symptomatic efficacy of beidellitic montmorillonite in irritable
bowel syndrome: a randomized, controlled trial.
Ducrotte P, Dapoigny M, Bonaz B, Siproudhis L.
Digestive Tract Research Group EA 3234/IFRMP23, Rouen University Hospital,
France. philippe.ducrotte@chu-rouen.fr
BACKGROUND: Beidellitic montmorillonite is a purified clay containing a double
aluminium and magnesium silicate. AIM: To assess the efficacy and the safety of
beidellitic montmorillonite (3 g, t.d. for 8 weeks) in patients with irritable
bowel syndrome (IBS). METHODS: A multicentre, double-blind, placebo-controlled,
randomized study with parallel groups, was performed in IBS patients selected
according to ROME I criteria. Patients were included after a 1-week washout
period to confirm that abdominal pain and/or discomfort was rated at least 2 on
a 0-4 graded Likert scale. Patients were then randomized and stratified
according to their predominant bowel habit profile into three groups. The use of
rescue medication was allowed: polyethylene glycol 4000 (10-20 g/day) as a
laxative agent in case of stool absence for three consecutive days,
phloroglucinol (80 to a maximum of 320 mg/day) as a spasmolytic agent for no
more than 8 days. The main end-point was the improvement of abdominal pain
and/or discomfort by at least 1 point on the Likert scale. RESULTS: A total of
524 patients constituted the overall intent-to-treat population (ITT), 263 were
assessed in the beidellitic montmorillonite group, i.e. 93 diarrhoea-predominant
IBS (D-IBS), 83 constipation-predominant IBS (C-IBS), 87 alternating
constipation/diarrhoea-IBS (A-IBS); 261 in the placebo group, i.e. 81 D-IBS, 92
C-IBS and 88 A-IBS. Initial analysis in the ITT population demonstrated a higher
rate of success with beidellitic montmorillonite (51.7%) when compared with the
placebo group (45.2%); however, the difference was not statistically
significant. Improvement was significant in C-IBS both in ITT (beidellitic
montmorillonite group = 49.4%, placebo group = 31.5%, P < 0.016) and per
protocol populations (59.4% vs. 37.8%) (P < 0.01). The time to improvement of
abdominal pain and/or discomfort (log Rank test) was also significantly in
favour of beidellitic montmorillonite, (P < 0.04). The average number of stools
per day was not different from baseline, either in all patients or in C-IBS
patients. Spasmolytic and laxative agent intakes were not different between the
two groups. Subjective evaluation by patients of treatment efficacy and visual
analogue scale test of treatment efficacy by investigators were significantly
better in the beidellitic montmorillonite group (P < 0.05). Tolerance of
beidellitic montmorillonite was considered optimal without any significant
adverse event. CONCLUSIONS: Although pain or discomfort was not significantly
improved in the entire IBS population treated with beidellitic montmorillonite
in comparison with placebo, this study demonstrates that beidellitic
montmorillonite is efficient for C-IBS patients (P < 0.016). This effect of
beidellitic montmorillonite on pain cannot be explained by changes in bowel
habits. The efficacy of this well-tolerated therapy warrants further
confirmatory therapeutic trials in C-IBS patients.
-----
Hepatogastroenterology. 2004 Nov-Dec;51(60):1708-12.
Treatment of irritable bowel syndrome with colonic pacing:
evaluation of pacing parameters required for correction of the "tachyarrhythmia"
of the IBS.
Shafik A, Shafik AA, Ahmed I, el-Sibai O.
Department of Surgery and Experimental Research, Faculty of Medicine, Cairo
University, Cairo, Egypt. shafik@ahmed-shafik.org
BACKGROUND/AIMS: A recent study of the electromyographic (EMG) activity of
irritable bowel syndrome (IBS) has shown that the frequency, amplitude and
conduction velocity of the slow waves (SWs) of the sigmoid colon (SC) were
significantly higher in IBS patients than in the healthy volunteers. The SW
rhythm was irregular. A "tachyarrhythmic pattern" was characteristic of the IBS.
The SC pressure in the IBS was also significantly higher than that of the
healthy controls. We suggested that the cause of IBS is related to an aberrant
focus in one or more of the colonic pacemakers which possibly triggers abnormal
impulses to the colon. We hypothesized that stimulation of the pacemaker which
delivers electric waves to the SC, may correct the abnormal electric waves and
eliminate the IBS symptoms. In this communication we tried to define the
adequate pacing parameters necessary for normalization of the tachyarrhythmic
pattern of the electric waves in IBS. METHODOLOGY: Nineteen subjects with IBS
were divided into a study group (age 48.6+/-9.8 years; 7 women, 4 men) and a
control group (age 47.6+/-9.2 years; 5 women, 3 men). The study also included 8
healthy volunteers (47.9+/-9.7 years; 5 women). Three 28-gauge cardiac pacing
electrodes were used: one for pacing applied to the pacemaker at the colosigmoid
junction (CSJ) and 2 for recording applied to the SC mucosa. In the study group,
the CSJ electrode was stimulated using an electrical stimulator which delivered
a constant current. The optimal pacing parameters had been determined after
repeated trials with different variables. In the control group, recording was
done without pacemaker activation. The SC pressure was measured by a 10-F
saline-perfused tube. RESULTS: In the healthy volunteers, the basal SWs were
regular and followed or superimposed by action potentials (APs). Pacing produced
a significant increase in the SW variables and SC pressure; the latency was
20.3+/-3.6 s. The study and the control group exhibited a basal tachyarrhythmic
pattern and a significantly higher SC pressure than the healthy volunteers.
Pacing of the study group effected lowering of the SW variables and SC pressure
which did not show a significant difference against those of the healthy
volunteers at rest. The optimal pacing parameters comprised an amplitude of 6 mA,
a pulse width of 150 ms and a 25% higher frequency than that of the already
recorded basal colonic waves. The control group showed no change in the
tachyarrhythmic pattern. CONCLUSIONS: CS pacing parameters were identified and
succeeded in normalizing the tachyarrhythmic pattern of the IBS. We suggest that
this method be used for the treatment of patients with IBS when other measures
have failed to cure the condition.
-----
Aliment Pharmacol Ther. 2004 Nov;20 Suppl 7:25-30
Review article: the safety profile of tegaserod.
Schoenfeld P.
Division of Gastroenterology, University of Michigan School of Medicine,
Veterans Affairs Center for Excellence in Health Services Research, Ann Arbor,
MI, USA.
Summary Gastrointestinal symptoms are the most common side-effects of tegaserod
therapy. In data pooled from Phase III randomized controlled trials in patients
with irritable bowel syndrome with constipation, diarrhoea was reported by 8.8%
of patients treated with tegaserod 6 mg b.d. vs. 3.8% of patients treated with
placebo. Similar rates were observed in international post-US marketing
randomized controlled trials. In most patients, tegaserod-induced diarrhoea was
mild and transient. In randomized controlled trials, it did not elicit fluid or
electrolyte disturbances, and fewer than 3% of irritable bowel syndrome patients
discontinued tegaserod due to diarrhoea. The incidence of other gastrointestinal
symptoms (e.g. abdominal pain, nausea and flatulence) was similar in tegaserod-treated
and placebo-treated patients. Pooled analysis of Phase III and post-US marketing
randomized controlled trials did not demonstrate significant differences between
tegaserod-treated and placebo-treated patients in the incidence of
abdominal/pelvic surgery. No episodes of ischaemic colitis were reported in
tegaserod-using patients in any Phase III or post-marketing randomized
controlled trials, and post-marketing surveillance indicated that the rate of
ischaemic colitis in tegaserod-using patients was lower than that in non-tegaserod-using
patients. Pooled analysis of Phase III randomized controlled trials demonstrated
an increase in the incidence of headaches in tegaserod-treated (6 mg b.d.) vs.
placebo-treated patients (15% vs. 12.3%, respectively; P < 0.05), although
post-US marketing randomized controlled trials did not demonstrate this
increase. Other extra-gastrointestinal adverse events occurred with similar
frequency in tegaserod-treated and placebo-treated patients. Tegaserod-treated
patients in randomized controlled trials did not demonstrate significant
prolongation of the QT(c) interval or cardiac arrhythmias compared with
placebo-treated patients. In summary, tegaserod exhibits a favourable safety and
tolerability profile in irritable bowel syndrome patients based on data from
clinical trials.
-----
Expert Opin Pharmacother. 2004 Nov;5(11):2369-79.
Review of tegaserod in the treatment of irritable bowel syndrome.
Patel S, Berrada D, Lembo A.
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA
02215, USA.
Tegaserod is a drug in a new class of compounds called aminoguanidine indoles
and is structurally similar to serotonin (5-HT) with modifications that make the
drug selective for the 5-HT(4) receptor. Tegaserod has a stimulatory effect on
gastrointestinal (GI) motility that has been demonstrated in animal studies and
in healthy adults. Tegaserod also increases GI secretion and reduces rectal
sensitivity. Tegaserod is currently approved by the FDA for the treatment of
women with constipation-predominant irritable bowel syndrome (C-IBS). Eight
large Phase III clinical trials involving > 5000 IBS patients support the
clinical efficacy of tegaserod in this group of patients. Patients who were
treated with tegaserod had an overall improvement in IBS symptoms (Subject's
Assessment of Global Relief) as well as in secondary end points, such as
abdominal pain and discomfort, stool consistency, change in bowel movements and
relief of bloating. Tegaserod was well-tolerated. The most common adverse
reaction in clinical trials was diarrhoea, which was usually temporary and mild,
although severe diarrhoea requiring hospitalisation has been rarely (< 1%)
reported.
-----
Am J Gastroenterol. 2004 Nov;99(11):2195-203.
Long-term safety and efficacy of alosetron in women with severe
diarrhea-predominant irritable bowel syndrome.
Chey WD, Chey WY, Heath AT, Dukes GE, Carter EG, Northcutt A, Ameen VZ.
University of Michigan Medical Center, Ann Arbor, Michigan, USA.
OBJECTIVES: To assess long-term safety and efficacy of alosetron in women with
severe, chronic diarrhea-predominant IBS and in a subset having more frequent
urgency (i.e., bowel urgency at least 10 of 14 days during screening). METHODS:
Randomized patients received either alosetron 1 mg (n = 351) or placebo (n =
363) twice daily during a 48-wk, double-blind study. The primary endpoint was
the 48-wk average rate of adequate relief of IBS pain and discomfort. Secondary
endpoints included 48-wk average satisfactory control rates of urgency, stool
frequency, stool consistency, and bloating. Other efficacy endpoints were
average monthly adequate relief and urgency control rates and impact of provided
rescue medication. RESULTS: Alosetron-treated patients had significantly greater
48-wk average adequate relief (p= 0.01) and urgency control (p < 0.001) rates,
regardless of rescue medication use, compared with placebo. Results in subjects
with more frequent urgency were more robust than those in the overall population
(p= 0.005). In weeks without rescue medication use, satisfactory control rates
for stool frequency and stool consistency were significantly greater in
alosetron-treated patients than placebo. Alosetron-treated patients had
significantly greater adequate relief than placebo-treated patients (p < 0.05)
in 9 of 12 months and significantly greater urgency control (p < 0.001) in all
months. Adequate relief and urgency control were maintained throughout the
treatment. Adverse events and serious adverse events were similar between
treatment groups, except for constipation. Neither ischemic colitis nor serious
events related to bowel motor dysfunction was reported. CONCLUSIONS: Long-term
use of alosetron is effective and well-tolerated in women with chronic,
diarrhea-predominant IBS, including those with more frequent urgency.
-----
Clin Gastroenterol Hepatol. 2004 Nov;2(11):957-67.
Complementary and alternative medicine in gastroenterology: the
good, the bad, and the ugly.
Koretz RL, Rotblatt M.
Department of Medicine, Olive View--UCLA Medical Center, Sylmar, California
91342, USA. rkoretz@ladhs.org
A large proportion of the American population avails itself of a variety of
complementary and alternative medicine (CAM) interventions. Allopathic
practitioners often dismiss CAM because of distrust or a belief that there is no
sound scientific evidence that has established its utility. However, although
not widely appreciated, there are thousands of randomized controlled trials (RCTs)
that have addressed the efficacy of CAM. We reviewed the RCTs of herbal and
other natural products, acupuncture, and homeopathy as examples of typical CAM
modalities, focusing on conditions of interest to gastroenterologists.
Peppermint (alone or in combination) has supportive evidence for use in patients
with dyspepsia, irritable bowel syndrome, and as an intraluminal spasmolytic
agent during barium enemas or endoscopy. Ginger appeared to be effective in
relieving nausea and vomiting due to motion sickness or pregnancy. Probiotics
were useful in childhood diarrhea or in diarrhea due to antibiotics; one
particular formulation (VSL#3) prevented pouchitis. Acupuncture appeared to
ameliorate postoperative nausea and vomiting and might be useful elsewhere.
There is even a suggestion that homeopathy has efficacy in treatment of
gastrointestinal problems or symptoms. The major problem in interpreting these
CAM data is the generally low quality of the RCTs, although that quality might
not be different compared to RCTs in the general medical literature.
Gastroenterologists should become familiar with these techniques; it is likely
that their patients already are.
-----
BMC Fam Pract. 2004 Oct 13;5(1):22.
General practitioners believe that hypnotherapy could be a useful
treatment for irritable bowel syndrome in primary care.
Cox S, de Lusignan S, Chan T.
Gillets Surgery, Deanland Road, Balcome, West Sussex, RH17 6PH, UK. stephen.cox@gp-h82615.nhs.uk
<stephen.cox@gp-h82615.nhs.uk>
BACKGROUND: Irritable bowel syndrome is a common condition in general practice.
It occurs in 10 to 20% of the population, but less than half seek medical
assistance with the complaint. METHODS: A questionnaire was sent to the 406 GPs
listed on the West Sussex Health Authority Medical List to investigate their
views of this condition and whether they felt hypnotherapy had a place in its
management RESULTS: 38% of general practitioners responded. The achieved sample
shared the characteristics of target sample.Nearly half thought that irritable
bowel syndrome (IBS) was a "nervous complaint" and used a combination of "the
placebo effect of personal care," therapeutic, and dietary advice. There is
considerable divergence in the perceived effectiveness of current approaches.
Over 70% thought that hypnotherapy may have a role in the management of patients
with IBS; though the majority (68%) felt that this should not be offered by
general practitioners. 84% felt that this should be offered by qualified
hypnotherapist, with 40% feeling that this should be offered outside the health
service. CONCLUSIONS: General practitioners vary in their perceptions of what
constitutes effective therapy in IBS. They are willing to consider referral to a
qualified hypnotherapist.
-----
Aliment Pharmacol Ther. 2004 Oct 15;20(8):831-41.
Review article: therapeutic roles of acupuncture in functional
gastrointestinal disorders.
Ouyang H, Chen JD.
Transneuronix and Veterans Research and Education Foundation, Oklahoma City, OK,
USA.
Acupuncture has been practiced empirically in China for several millennia, and
is being increasingly accepted by practitioners and patients worldwide.
Functional gastrointestinal disorders are common in clinical gastroenterology.
The prevalence of one or more functional gastrointestinal disorders is estimated
to be as high as 70% in general population using Rome diagnostic criteria. Since
functional gastrointestinal disorders are diagnosed based on symptoms and the
exact aetiologies for most of functional gastrointestinal disorders are not
completely known, it is not unusual that the treatment for these disorders is
unsatisfactory and alternative therapies are attractive to both patients and
practitioners. During the latest decades, a considerable number of studies have
been performed on acupuncture for the treatment of functional gastrointestinal
disorders and underlying mechanisms. In this article, we reviewed available data
in the literature on the applications and mechanisms of acupuncture for the
treatment of functional gastrointestinal disorders, including functional
oesophageal disorders, nausea and vomiting, functional dyspepsia, irritable
bowel syndrome, constipation, etc. A summary is provided based on the quality
and quantity of published studies regarding the efficacy of acupuncture in
treating these various disorders. In addition, the methodology of acupuncture is
also introduced.
-----
Clin Gastroenterol Hepatol. 2004 Oct;2(10):895-904.
Effect of renzapride on transit in constipation-predominant
irritable bowel syndrome.
Camilleri M, McKinzie S, Fox J, Foxx-Orenstein A, Burton D, Thomforde G, Baxter
K, Zinsmeister AR.
Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.)
Program, Gastroenterology Research Unit, Mayo Clinic College of Medicine,
Rochester, Minnesota 55905, USA. camilleri.michael@mayo.edu
BACKGROUND & AIMS: The aim of this study was to evaluate the dose-ranging
pharmacodynamic effects of renzapride, a 5-hydroxytryptamine 4 (5-HT4) receptor
full agonist/5-HT3 receptor antagonist, on gastrointestinal transit and symptoms
in patients with constipation-predominant irritable bowel syndrome (C-IBS).
METHODS: Forty-eight patients (46 women) with C-IBS underwent recording of
baseline symptoms for 1 week. Twelve patients per group were randomized
(double-blind, parallel design) to 11-14 days of renzapride (1, 2, or 4 mg) or
placebo, once daily. Daily bowel habits and weekly satisfactory relief of IBS
symptoms were recorded. At the end of treatment, gastric emptying (GE), small
bowel transit (SBT), and colon transit (CT) were measured by scintigraphy. The
relationship between CT and bowel function was evaluated. RESULTS: A
statistically significant linear dose response to renzapride was detected for CT
(GC8 h, P = 0.004; GC24 h, P = 0.056), and ascending colon (AC) emptying t1/2 (P
= 0.019), but not for GE (t1/2, P = 0.088; or SBT, P = 0.41). AC half-time
transit (t1/2) for placebo and 4 mg of renzapride were (median) 17.5 vs. 5.0
hours, respectively. Improved bowel function scores (stool form and ease of
passage, but not frequency) were significantly (P < 0.05) associated with
accelerated CT. Pharmacokinetic analysis showed linear kinetics of renzapride
with a mean t1/2 in plasma of 10 hours. Bowel function and satisfactory relief
were not significantly altered by renzapride, although a type II error cannot be
excluded. No significant adverse clinical, laboratory, or electrocardiogram (ECG)
effects were observed. CONCLUSIONS: Renzapride causes clinically significant
dose-related acceleration of CT, particularly ascending colonic emptying; this
acceleration of transit is associated with improvement of bowel function in
female C-IBS patients.
-----
Minerva Med. 2004 Oct;95(5):427-41.
Diagnostic and therapeutic strategies in the irritable bowel
syndrome.
Cremonini F, Talley NJ.
Clinical Enteric Neuroscience Translational and Epidemiological Research,
(CENTER) Program, Mayo Clinic, Rochester, MN, USA.
The management of patients with irritable bowel syndrome (IBS) is a frequent,
yet challenging task in both primary care and gastroenterology practice. A
diagnostic strategy guided by keen clinical judgment should focus on positive
symptom criteria and on the absence of alarm symptoms. In younger patients
lacking alarm features, invasive testing has a low-yield. The presence of food
intolerance and underlying celiac disease should be excluded. The usefulness of
fecal tests such as calprotectin and lactoferrin to exclude organic bowel
disease is not adequately established. In patients with moderate to severe
symptoms who fail initial therapeutic trials, further tests can be performed in
tertiary care settings, such as transit measurement and tests for diagnosing
pelvic floor dysfunction. Treatment strategies for IBS are currently directed at
the predominant symptoms. In diarrhea-predominant IBS, opioids (e.g. loperamide)
and the 5-HT(3) receptor antagonist alosetron are efficacious. In
constipation-predominant IBS, fiber and bulk laxatives are traditionally used,
but their efficacy is variable and may worsen symptoms. The 5-HT(4) receptor
agonist tegaserod is efficacious in female patients with IBS and constipation.
In patients with IBS and abdominal pain, antispasmodics and antidepressants can
be used, with the best evidence supporting the prescription of tricyclic
antidepressants. The efficacy of psychological treatments in terms of relieving
the symptoms of IBS is still uncertain. Limited evidence suggests that anti-enkephalinase
agents, somatostatin analogues, alpha(2)-receptor agonists, opioid antagonists,
selective serotonin reuptake inhibitors, probiotics and herbal treatments may be
useful in IBS patients.
-----
Am J Gastroenterol. 2004 Oct;99(10):1990-7.
Acupuncture has a placebo effect on rectal perception but not on
distensibility and spatial summation: a study in health and IBS.
Rohrbock RB, Hammer J, Vogelsang H, Talley NJ, Hammer HF.
Abteilung fur Gastroenterologie und Hepatologie, University of Vienna, Austria.
BACKGROUND: Recent data suggest that acupuncture has effects on gut physiology
and perception. Spatial summation is a central mechanism of perception and
describes the phenomenon that thresholds for perception are lower if more
receptors are stimulated. OBJECTIVES: We assessed perception thresholds for
rectal distension and cutaneous referral of symptoms, while inflating one or two
rectal balloons and the effect of both electro-acupuncture and
placebo-acupuncture on rectal distensibility, perception, and spatial summation.
METHODS: A tube with two barostat balloons was placed in the rectum of 12
healthy subjects and nine irritable bowel syndrome (IBS) patients with rectal
symptoms. Volume-controlled stepwise distension of the distal balloon only or
both balloons was performed first as a control, and thereafter with simultaneous
placebo- or electro-acupuncture in dermatomes S3 and S4. A symptom questionnaire
and anatomic questionnaire was completed during each distension. RESULTS: Rectal
elastance increased from 42.0 +/- 19.6 log mmHg/ml during one-balloon distension
to 59.6 +/- 33.1 log mmHg/ml during two-balloon distension (p < 0.05) in healthy
subjects, and from 48.8 +/- 14.4 log mmHg/ml (one balloon) to 77.6 +/- 24.2 log
mmHg/ml (p < 0.001) in patients with IBS. Electro-acupuncture had no effect on
rectal sensation, elastance, and cutaneous referral when compared to
placebo-acupuncture. However, acupuncture (both electro- and placebo-) increased
volume thresholds for sensation compared to control experiments, while objective
parameters like rectal tone and elastance were unaltered. CONCLUSION:
Acupuncture has a placebo effect on rectal perception but has no effect on
rectal distensibility and visceral referral. Spatial summation affected both
rectum distensibility and perception, but was also not altered by acupuncture.
-----
Nutrition. 2004 Sep;20(9):735-7.
Effects of a high-fiber diet on symptoms of irritable bowel
syndrome: a randomized clinical trial.
Aller R, de Luis DA, Izaola O, la Calle F, del Olmo L, Fernandez L, Arranz T,
Gonzalez Hernandez JM.
Institute of Endocrinology and Nutrition, Medical School, University of
Valladolid, Spain.
OBJECTIVE: We investigated the effects of dietary fiber on symptoms of irritable
bowel syndrome. METHODS: A single-blind randomized clinical trial was designed.
Fifty-six subjects with irritable bowel syndrome were prospectively and randomly
assigned to one of two groups: group 1 received a diet containing 10.4 g/d of
fiber and group 2 received a diet containing 30.5 g/d of fiber. Patients' body
weights, nutritional intakes as assessed with 3-d written food records, and
symptom scores were assessed at baseline and at 3 mo. RESULTS: There were no
dropouts during the study. Total energy intake and the distribution of
macronutrients were not significantly different between groups. Total dietary
fiber intake did not reach recommended levels in either group but was higher in
group 2 than in group 1 (25.95 +/- 2.12 g/d versus 6.06 +/- 2.7 g/d, P < 0.05).
Initial fiber intake did not differ significantly between groups. Pain scores,
bowel scores, and general scores improved in both groups (from baseline to 3
mo), and no significant differences were detected between groups. CONCLUSIONS: A
modest fiber intake in patients with irritable bowel syndrome relieved symptoms,
but this therapeutic benefit of fiber may have been due to a placebo effect
because the results were similar in the low-fiber group.
-----
J Altern Complement Med. 2004 Aug;10(4):667-9.
Artichoke leaf extract reduces symptoms of irritable bowel
syndrome and improves quality of life in otherwise healthy volunteers suffering
from concomitant dyspepsia: a subset analysis.
Bundy R, Walker AF, Middleton RW, Marakis G, Booth JC.
Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The
University of Reading, Reading, UK.
OBJECTIVES: Does artichoke leaf extract (ALE) ameliorate symptoms of Irritable
bowel syndrome (IBS) in otherwise healthy volunteers suffering concomitant
dyspepsia? METHODS: A subset analysis of a previous dose-ranging, open, postal
study, in adults suffering dyspepsia. Two hundred and eight (208) adults were
identified post hoc as suffering with IBS. IBS incidence, self-reported usual
bowel pattern, and the Nepean Dyspepsia Index (NDI) were compared before and
after a 2-month intervention period. RESULTS: There was a significant fall in
IBS incidence of 26.4% (p < 0.001) after treatment. A significant shift in
self-reported usual bowel pattern away from "alternating constipation/diarrhea"
toward "normal" (p < 0.001) was observed. NDI total symptom score significantly
decreased by 41% (p < 0.001) after treatment. Similarly, there was a significant
20% improvement in the NDI total quality-of-life (QOL) score in the subset after
treatment. CONCLUSION: This report supports previous findings that ALE
ameliorates symptoms of IBS, plus improves health-related QOL.
-----
Best Pract Res Clin Gastroenterol. 2004 Aug;18(4):773-86.
Treatment options in irritable bowel syndrome.
Farthing MJ.
St George's Hospital Medical School, Cranmer Terrace, Tooting, London SW17 0RE,
UK.
The irritable bowel syndrome (IBS) is part of the spectrum of functional bowel
disorders characterised by a diverse consortium of abdominal symptoms including
abdominal pain, altered bowel function (bowel frequency and/or constipation),
bloating, abdominal distension, the sensation of incomplete evacuation and the
increased passage of mucus. It is not surprising therefore that no single,
unifying mechanism has as yet been put forward to explain symptom production in
IBS. The currently favoured model includes both central and end-organ components
which may be combined to create an integrated hypothesis incorporating
psychological factors (stress, distress, affective disorder) with end-organ
dysfunction (motility disorder, visceral hypersensitivity) possibly aggravated
by sub-clinical inflammation as a residuum of an intestinal infection. There is
currently no universally effective therapy for IBS. Standard therapy generally
involves a symptom-directed approach; anti-diarrhoeal agents for bowel
frequency, soluble fibre or laxatives for constipation and smooth muscle
relaxants and anti-spasmodics for pain. New drug development has focused
predominantly on agents that modify the effects of 5-hydroxytryptamine (5-HT) in
the gut, principally the 5-HT(3) receptor antagonists for painful diarrhoea
predominant IBS and 5-HT(4) agonists for constipation predominant IBS. More
speculative new therapeutic approaches include anti-inflammatory agents,
antibiotics, probiotics, antagonists of CCK1 receptors, tachykinins and other
novel neuronal receptors.
-----
Curr Opin Investig Drugs. 2004 Jul;5(7):736-42.
Antidepressants in the treatment of irritable bowel syndrome and
visceral pain syndromes.
Crowell MD, Jones MP, Harris LA, Dineen TN, Schettler VA, Olden KW.
Division of Gastroenterology, Mayo Clinic College of Medicine and Mayo
Foundation, Scottsdale, AZ 85259, USA. crowell.michael@mayo.edu
Irritable bowel syndrome (IBS) is characterized by abdominal pain associated
with disordered defecation, which may include urgency and altered stool
frequency. Visceral pain syndromes, including IBS, may be effectively treated by
a variety of therapies that modulate the interactions between the central and
enteric nervous systems. Clinical observations and preliminary data suggest that
antidepressants may be efficacious for the treatment of these syndromes. The
tricyclic antidepressants (TCAs) have been utilized most extensively in this
area, but there is a need for more rigorous efficacy data. Serotonin, an
important neurotransmitter in both the central and enteric nervous systems,
modifies both motility and sensation in the gut. Recognition of the importance
of serotonin in digestive motility and sensation has sparked interest in the use
of agents that modify serotonergic transmission in visceral pain syndromes.
Pharmacological therapeutics that modulate the biological amines (serotonin,
norepinephrine, dopamine and catecholamines) both peripherally and within the
central nervous system may offer more effective therapies for these disorders.
The selective serotonin reuptake inhibitors are commonly used in clinical
practice, but more rigorous, controlled studies are needed to determine their
effects beyond the treatment of psychiatric comorbidity. The newer generation
antidepressants may provide additional insight into the pathophysiology of the
brain-gut interactions and their relationship to functional bowel disorders,
providing new therapeutic interventions.
-----
Aliment Pharmacol Ther. 2004 Jul 15;20(2):237-46.
Effect of asimadoline, a kappa opioid agonist, on pain induced by
colonic distension in patients with irritable bowel syndrome.
Delvaux M, Beck A, Jacob J, Bouzamondo H, Weber FT, Frexinos J.
Gastroenterology Department, CHU Rangueil, Toulouse, France. 106521.3337@compuserve.com
BACKGROUND: Visceral hypersensitivity plays a major role in irritable bowel
syndrome pathophysiology. Opioid kappa receptors on afferent nerves may modulate
it and be the target for new irritable bowel syndrome treatments. AIM: This
study evaluated the effect of the kappa opioid agonist asimadoline on perception
of colonic distension and colonic compliance in irritable bowel syndrome
patients. METHOD: Twenty irritable bowel syndrome female patients (Rome II
criteria; 40 +/- 13 years) and hypersensitivity to colonic distension (Pain
threshold < or = 32 mmHg) were included in a randomized double-blind cross-over
trial comparing the effect of a single oral dose of asimadoline 0.5 mg or
placebo on sensory thresholds (defined as a constant and sustained sensation)
elicited by left colon phasic distension (5 mmHg steps, 5 min) up to a sensation
of abdominal pain. Colonic compliance was compared by the slope of the
pressure-volume curves. RESULTS: On asimadoline, pain threshold (mean +/- s.d.)
(29.8 +/- 7.2 mmHg) was higher than on placebo (26.3 +/- 7.8 mmHg), difference
not statistically significant (P = 0.1756, ANOVA). Area under curve of pain
intensity rated at each distension step was significantly lower on asimadoline
(89.3 +/- 33.9, ANOVA) than on placebo (108.1 +/- 29.7) (P = 0.0411). Thresholds
of perception of nonpainful distensions were not altered on asimadoline, as
compared with placebo. Colonic compliance was not different on placebo and
asimadoline. CONCLUSION: Asimadoline decreases overall perception of pain over a
wide range of pressure distension of the colon in irritable bowel syndrome
patients, without altering its compliance. These data suggest that further
studies should explore the potential benefit of asimadoline in treatment of pain
in irritable bowel syndrome patients.
-----
Drug Saf. 2004;27(9):619-31.
Safety profile of tegaserod, a 5-HT4 receptor agonist, for the
treatment of irritable bowel syndrome.
Hasler WL, Schoenfeld P.
Division of Gastroenterology, University of Michigan School of Medicine, Ann
Arbor, Michigan, USA. whasler@umich.edu
This article reviews the safety and tolerability profile of tegaserod, a novel
selective partial agonist of the serotonin 5-HT(4) receptor. Tegaserod was
recently approved for the treatment of women with irritable bowel syndrome (IBS)
with constipation.Tegaserod exhibits rapid absorption from the small intestine,
and is excreted unchanged in the faeces and as metabolites in the urine. Meal
ingestion decreases its bioavailability. There is little effect of age or gender
on pharmacokinetics, although plasma levels may be slightly higher in the
elderly. Tegaserod has no effect on plasma levels of other drugs metabolised by
cytochrome P450 enzyme systems.Gastrointestinal symptoms are the most common
adverse effects of tegaserod therapy. In data pooled from phase III randomised
controlled trials (RCTs) in IBS with constipation patients, diarrhoea was
reported by 8.8% of patients treated with tegaserod 6mg twice daily versus 3.8%
of patients receiving placebo. Similar rates have been observed in international
post-US marketing RCTs. In most patients, tegaserod-induced diarrhoea was mild
and transient. In RCTs, it did not elicit fluid or electrolyte disturbances, and
fewer than 3% of IBS patients discontinued tegaserod due to diarrhoea. Since its
release, rare cases of more severe diarrhoea and ischaemic colitis have been
reported. The incidence of other gastrointestinal symptoms (e.g. abdominal pain,
nausea, and flatulence) has been similar among tegaserod-treated patients and
placebo-treated patients. Pooled analysis of phase III RCTs and post-US
marketing RCTs have not demonstrated significant differences between tegaserod-treated
patients and placebo-treated patients in the incidence of abdominal-pelvic
surgery. There is no convincing evidence that rebound gastrointestinal symptoms
occur upon termination of tegaserod therapy.Pooled analysis of phase III RCTs
demonstrated an increase in the incidence of headaches among tegaserod-treated
patients (6mg twice daily) compared with placebo-treated patients (15% vs 12.3%,
respectively, p < 0.05), although post-US marketing RCTs have not observed this
increase. Other extra-gastrointestinal adverse events occur with similar
frequency among tegaserod-treated patients and placebo-treated patients.
Tegaserod-treated patients in RCTs have not demonstrated significant
prolongation of the QTc interval or cardiac arrhythmias compared with
placebo-treated patients. Supra-therapeutic doses in healthy volunteers did not
effect electrocardiographic parameters. Laboratory parameters are mostly
unaffected by tegaserod, although several individuals have exhibited increased
eosinophil counts.In summary, tegaserod exhibits a favourable safety and
tolerability profile in IBS patients based on data from clinical trials.
Diarrhoea is the most common adverse event associated with tegaserod use.
Continued post-US marketing surveillance will further define the safety and
tolerability profile of tegaserod.
-----
Clin Gastroenterol Hepatol. 2004 Jul;2(7):585-96.
Self-management for women with irritable bowel syndrome.
Heitkemper MM, Jarrett ME, Levy RL, Cain KC, Burr RL, Feld A, Barney P, Weisman
P.
Department of Behavioral Nursing and Health Systems, University of Washington,
Seattle, 98195, USA. heit@u.washington.edu
BACKGROUND & AIMS: A randomized clinical trial was used to test the
effectiveness of an 8-session multicomponent program (Comprehensive) compared to
a Brief (single session) version and Usual Care for women with irritable bowel
syndrome. METHODS: Menstruating women, ages 18-48 years, were recruited from a
health maintenance organization as well as community advertisements. Psychiatric
nurse practitioners delivered both programs. The primary outcomes were improved
symptoms, psychological distress, health-related quality of life, and indicators
of stress-related hormones. Outcome indicators were measured at 3 points: (1)
immediately after the Comprehensive program or 9 weeks after entry into the
Usual Care and Brief Self-Management groups, (2) at 6 months, and (3) at 12
months. RESULTS: Compared to Usual Care, women in the Comprehensive program had
reduced gastrointestinal symptoms, psychological distress indicators,
interruptions in activities because of symptoms, and enhanced quality of life
that persisted at the 12-month follow-up evaluation. Women in the Brief group
also demonstrated statistically significant improvements in quality of life and
smaller nonsignificant improvements in other outcome variables than observed in
the Comprehensive group. There were no group differences in urine catecholamines
and cortisol levels. CONCLUSIONS: A comprehensive self-management program is an
important therapy approach for women with irritable bowel syndrome. The Brief
1-session version is also moderately helpful for some women with IBS.
-----
J Clin Gastroenterol. 2004 Jul;38(6 Suppl):S104-6.
Probiotics in the treatment of irritable bowel syndrome.
Saggioro A.
Digestive Diseases, Hepatology and Clinical Nutrition Department, Umberto I
Hospital, Venice, Italy. asaggioro@hotmail.com
Irritable Bowel Syndrome (IBS) may be diagnosed on the presence of symptoms,
according to Rome II criteria and some studies have shown that abnormal colonic
fermentation may be an important factor in the development of symptoms in some
patients with IBS. Since the fermentations of substrates by the intestinal flora
may play a key role in the use of probiotics in the treatment of IBS, fifty
patients (24 males, 26 females), mean age 40 years (range = 26-64 years) with
IBS, according to Rome II criteria, were enrolled into the study after informed
consensus. Patients were randomly assigned to receive either the active
preparation containing Lactobacillus Plantarum LP0 1 and Bifidocterium Breve BR0
both at a concentration of 5 x 10 CFU/ml, or placebo powder containing starch
identical to the study product, for 4 weeks. To evaluate treatment efficacy two
different scores were considered: Pain score in different abdominal locations
after treatment decreased in probiotics group of 38% versus 18% (P < 0.05) of
placebo group after 14 days and of 52% versus 11% (P < 0.001) after 28 days. The
severity score of characteristic IBD symptoms significantly decreased in
probiotic group versus placebo group after 14 days 49.6% versus 9.9% (P < 0.001)
and these data were confirmed after 28 days (44.4% versus 8.5%, P < 0.001). In
conclusion, short-term therapy with Lactobacillus PlantarumLP0 1 and
Bifidocterium Breve BR0 may be considered a promising approach to the therapy
for IBS.
-----
J Clin Gastroenterol. 2004 Jul;38(6):475-83.
Bacteriotherapy using fecal flora: toying with human motions.
Borody TJ, Warren EF, Leis SM, Surace R, Ashman O, Siarakas S.
Centre for Digestive Diseases, Sydney, Australia. tborody@zip.com.au
The intestinal flora may play a key role in the pathogenesis of certain
gastrointestinal (GI) diseases. Components of bowel flora such as Lactobacillus
acidophilus and Bifidobacterium bifidus have long been used empirically as
therapeutic agents for GI disorders. More complex combinations of probiotics for
therapeutic bacteriotherapy have also recently become available, however the
most elaborate mix of human-derived probiotic bacteria is, by definition, the
entire fecal flora. Fecal bacteriotherapy uses the complete normal human flora
as a therapeutic probiotic mixture of living organisms. This type of
bacteriotherapy has a longstanding history in animal health and has been used
sporadically against chronic infections of the bowel, especially as a treatment
of last resort for patients with severe Clostridium difficile syndromes
including recurrent diarrhea, colitis, and pseudomembranous colitis. Encouraging
results have also been observed following infusions of human fecal flora in
patients with inflammatory bowel disease, irritable bowel syndrome, and chronic
constipation. The therapeutic use of fecal bacteriotherapy is reviewed here and
possible mechanisms of action and potential applications explored. Published
reports on fecal bacteriotherapy are few in number, and detail the results of
small uncontrolled open studies and case reports. Nevertheless, given the
promising clinical responses, formal research into fecal bacteriotherapy is now
warranted.
-----
J Gastroenterol Hepatol. 2004 Jul;19(7):744-9.
Cisapride treatment of constipation-predominant irritable bowel
syndrome is not superior to placebo.
Ziegenhagen DJ, Kruis W.
Department of Internal Medicine and Gastroenterology, Evangelisches Krankenhaus
Koeln-Kalk, Academic Hospital of Cologne University, Cologne, Germany.
dr.dieter.ziegenhagen@dkv.com
BACKGROUND AND AIM: Previous studies with cisapride reported conflicting results
in patients with constipation-predominant irritable bowel syndrome (IBS). To
gain further evidence, this randomized double-blind study was carried out.
METHODS: Eighty-two symptomatic outpatients were randomized to receive either 5
mg oral cisapride or placebo three times daily for a period of 12 weeks. In
patients without satisfactory improvement after 4 weeks, the dose was doubled.
Symptom evaluation used visual analog scales (VAS) and the investigators' global
assessment. RESULTS: After 4 weeks, in 18 (45%) cisapride and 24 (57%) placebo
patients the dose was doubled because of insufficient improvement of symptoms.
The mean VAS score for patients' global rating of IBS symptoms at baseline was
67.5 mm for cisapride versus 70.7 mm for placebo, and improved to 38.4 mm versus
44.5 mm after 12 weeks of treatment. Investigators rated the overall effect of
therapy as good or excellent in 70% of the cisapride and 50% of the placebo
group. Neither these nor further efficacy parameter differences reached
statistical significance. CONCLUSIONS: These results indicate that the effect of
15-30 mg cisapride daily on symptoms of constipation-predominant IBS is not
significantly superior to placebo. During the 12 week treatment of this trial
cisapride proved to be safe and tolerable.
-----
Intern Med. 2004 May;43(5):353-9.
Management of irritable bowel syndrome.
Torii A, Toda G.
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo
105-0003.
Irritable bowel syndrome (IBS) is one of the most common functional
gastrointestinal disorders. The prevalence rate is 10-20% and women have a
higher prevalence. IBS adversely affects quality of life and is associated with
health care use and costs. IBS comprises a group of functional bowel disorders
in which abdominal discomfort or pain is associated with defecation or a change
in bowel habit, and with features of disordered defecation. The consensus
definition and criteria for IBS have been formalized in the "Rome II criteria".
Food, psychiatric disorders, and gastroenteritis are risk factors for developing
IBS. The mechanism in IBS involves biopsychosocial disorders; psychosocial
factors, altered motility, and heightened sensory function. Brain-gut
interaction is the most important in understanding the pathophysiology of IBS.
Effective management requires an effective physician-patient relationship.
Dietary treatment, lifestyle therapy, behavioral therapy, and pharmacologic
therapy play a major role in treating IBS. Calcium polycarbophil can benefit IBS
patients with constipation or alternating diarrhea and constipation.
-----
Scand J Gastroenterol. 2004 Feb;39(2):119-26.
A double-blind, placebo-controlled, randomized
study to evaluate the efficacy, safety and tolerability of tegaserod
in patients with irritable bowel syndrome.
Nyhlin H, Bang C, Elsborg L, Silvennoinen J, Holme I, Ruegg
P, Jones J, Wagner A.
Ersta Hospital, Stockholm, Sweden.
BACKGROUND: Tegaserod has been shown to be an effective therapy
for the multiple symptoms of irritable bowel syndrome (IBS) in
Western and Asia-Pacific populations. This study evaluated the
efficacy, safety and tolerability of tegaserod versus placebo
in patients with IBS. METHODS: Patients with IBS (excluding those
whose primary bowel symptom was diarrhoea) were randomized to
receive either tegaserod 6 mg b.i.d. (n = 327) or placebo (n =
320) for a 12-week double-blind treatment period. The primary
efficacy variable (over weeks 1 to 4) was the response to the
question: 'Over the past week do you consider that you have had
satisfactory relief from your IBS symptoms?' Secondary efficacy
variables assessed overall satisfactory relief over 12 weeks and
the individual IBS symptoms. RESULTS: Overall satisfactory relief
was greater in the tegaserod group than in the placebo group.
Over weeks I to 4, the odds ratio was 1.54, that is, the odds
of satisfactory relief were 54% higher in the tegaserod group
than in the placebo group (95% confidence interval for odds ratio
(CI) (1.14, 2.08), P = 0.0049). Over weeks 1 to 12, the odds ratio
was 1.78, that is, the odds of satisfactory relief were 78% higher
in the tegaserod group than in the placebo group (95% CI (1.35,
2.34), P < 0.0001). A statistically significant therapeutic
gain over placebo was observed for the majority of weeks from
week 1 to week 12 (except weeks I and 4), with a mean therapeutic
gain of 7.3 and 10.6 percentage points over weeks 1-4 and weeks
1-12, respectively. Headache was the most commonly reported adverse
event (8.0% tegaserod versus 4.7% placebo). Diarrhoea was reported
by 9.2% of patients on tegaserod (1.3% on placebo) and led to
discontinuation in 2.8% of tegaserod patients. CONCLUSION: Tegaserod
6 mg b.i.d. is an effective, safe and well-tolerated treatment
in patients suffering from IBS without diarrhoea as primary bowel
symptom.
-----
Aliment Pharmacol Ther. 2004 Feb 1;19(3):271-9.
Treatment of irritable bowel syndrome with herbal
preparations: results of a double-blind, randomized, placebo-controlled,
multi-centre trial.
Madisch A, Holtmann G, Plein K, Hotz J.
Medical Department I, Technical University Hospital, Dresden,
Germany.
BACKGROUND: Herbal medications have been used in many countries
for the treatment of patients with irritable bowel syndrome. Controlled
data supporting the efficacy of these treatments in patients with
irritable bowel syndrome are lacking. AIM: To assess the efficacy
and safety of a commercially available herbal preparation (STW
5) (nine plant extracts), the research herbal preparation STW
5-II (six plant extracts) and the bitter candytuft mono-extract
in patients with irritable bowel syndrome. METHODS: Two hundred
and eight patients with irritable bowel syndrome were recruited
after standardized diagnostic work-up into a double-blind, placebo-controlled,
multi-centre trial and were randomly assigned to receive one of
four treatments: commercially available herbal preparation STW
5 (n = 51), research herbal preparation STW 5-II (n = 52), bitter
candytuft mono-extract (n = 53) or placebo (n = 52). The main
outcome variables were the changes in total abdominal pain and
irritable bowel syndrome symptom scores. RESULTS: Two hundred
and three patients completed the trial. STW 5 and STW 5-II were
significantly better than placebo in reducing the total abdominal
pain score (intention-to-treat: STW 5, P = 0.0009; STW 5-II, P
= 0.0005) and the irritable bowel syndrome symptom score (intention-to-treat:
STW 5, P = 0.001; STW 5-II, P = 0.0003) at 4 weeks. There were
no statistically significant differences between the bitter candytuft
mono-extract group and the placebo group (P = 0.1473, P = 0.1207).
CONCLUSIONS: The commercially available herbal preparation STW
5 and its research preparation STW 5-II are both effective in
alleviating irritable bowel syndrome symptoms.
-----
Arch Intern Med 2003 Feb 10;163(3):265-74
A systematic review of alternative therapies in
the irritable bowel syndrome.
Spanier JA, Howden CW, Jones MP.
Department of Internal Medicine, Northwestern Memorial Hospital,
251 E Huron, Galter 4-104, Chicago, IL 60611, USA.
The irritable bowel syndrome is a common disorder associated
with a significant burden of illness, poor quality of life, high
rates of absenteeism, and high health care utilization. Management
can be difficult and treatment unrewarding; these facts have led
physicians and patients toward alternative therapies. We explored
a variety of treatments that exist beyond the scope of commonly
used therapies for irritable bowel syndrome. Guarded optimism
exists for traditional Chinese medicine and psychological therapies,
but further well-designed trials are needed. Oral cromolyn sodium
may be useful in chronic unexplained diarrhea and appears as effective
as and safer than elimination diets. The roles of lactose and
fructose intolerance remain poorly understood. Alterations of
enteric flora may play a role in irritable bowel syndrome, but
supporting evidence for bacterial overgrowth or probiotic therapy
is lacking.
-----
Am J Gastroenterol 2003 Feb;98(2):412-9
Normalization of lactulose breath testing correlates
with symptom improvement in irritable bowel syndrome. a double-blind,
randomized, placebo-controlled study.
Pimentel M, Chow EJ, Lin HC.
GI Motility Program, Department of Medicine, CSMC Burns and Allen
Research Institute, Cedars-Sinai Medical Center, Los Angeles,
CA 90048, USA.
OBJECTIVE: We have recently found an association between abnormal
lactulose breath test (LBT) findings and irritable bowel syndrome
(IBS). The current study was designed to test the effect of antibiotic
treatment for IBS in a double-blind fashion. METHODS: Consecutive
IBS subjects underwent an LBT with the results blinded. All subjects
were subsequently randomized into two treatment groups (neomycin
or placebo). The prevalence of abnormal LBT was compared with
a gender-matched control group. Seven days after completion of
treatment, subjects returned for repeat LBT. A symptom questionnaire
was administered on both days. RESULTS: After exclusion criteria
were met, 111 IBS subjects (55 neomycin, 56 placebo) entered the
study, with 84% having an abnormal LBT, compared with 20% in healthy
controls (p < 0.01). In an intention-to-treat analysis of all
111 subjects, neomycin resulted in a 35.0% improvement in a composite
score, compared with 11.4% for placebo (p < 0.05). Additionally,
patients reported a percent bowel normalization of 35.3% after
neomycin, compared with 13.9% for placebo (p < 0.001). There
was a graded response to treatment, such that the best outcome
was observed if neomycin was successful in normalizing the LBT
(75% improvement) (one-way ANOVA, p < 0.0001). LBT gas production
was associated with IBS subgroup, such that methane excretion
was 100% associated with constipation-predominant IBS. Methane
excretors had a mean constipation severity of 4.1, compared with
2.3 in all other subjects (p < 0.001). CONCLUSIONS: An abnormal
LBT is common in subjects with IBS. Normalization of LBT with
neomycin leads to a significant reduction in IBS symptoms. The
type of gas seen on LBT is also associated with IBS subgroup.
-----
Am J Gastroenterol 2002 Dec;97(12):3139-46
Patient satisfaction with alosetron for the treatment
of women with diarrhea-predominant
irritable bowel syndrome.
Olden K, DeGarmo RG, Jhingran P, Bagby B, Decker C, Markowitz
M, Carter E, Bobbitt W, Dahdul A, DeCastro E, Gringeri L, Johanson
J, Levinson L, Mula G, Poleynard G, Stoltz RR, Truesdale R, Young
D; Lotronex Investigator Team.
Mayo Clinic Scottsdale, Scottsdale, Arizona, USA.
OBJECTIVE: The efficacy and tolerability of alosetron in women
with diarrhea-predominant irritable bowel syndrome (IBS) have
been established in double-blind, placebo-controlled trials. However,
the degree to which alosetron fulfills the needs of those suffering
from IBS has not been thoroughly examined from the patient's perspective.
This randomized, double-blind, placebo-controlled study conducted
in women with diarrhea-predominant IBS evaluated patients' overall
satisfaction with treatment as well as their satisfaction with
respect to several specific medication attributes. METHODS: Patients
randomized to receive either alosetron 1 mg b.id. (n = 532) or
placebo (n = 269) were administered a questionnaire on which they
rated on 7-point Likert scales their prestudy IBS treatment (at
the screening visit) or study medication (on wk 12 or final study
visit) with respect to overall satisfaction and 11 specific medication
attributes. RESULTS: Whereas approximately 10% of patients were
satisfied or very satisfied overall with prestudy IBS medication,
69% of patients were satisfied or very satisfied overall with
alosetron and 46% with placebo (p < 0.001) at the end of 12
wk of therapy. The majority of alosetron-treated patients (61-87%)
were satisfied or very satisfied with each of 11 specific medication
attributes (p < 0.001 vs placebo for each attribute). Favorable
satisfaction ratings for alosetron were assigned to the five medication
attributes that patients considered to be most important, including
relief of urgency (68% alosetron vs 41% placebo), speed of relief
(71% vs 40%), time to return to normal activities (75% vs 49%),
relief of abdominal pain (62% vs 44%), and prevention of return
of urgency (68% vs 42%). CONCLUSIONS: Women with diarrhea-predominant
IBS are satisfied with alosetron 1 mg b.i.d. treatment overall
and also with respect to specific attributes of IBS medication
they consider most important.
-----
Am Fam Physician 2002 Nov 15;66(10):1867-74
Management of irritable bowel syndrome.
Viera AJ, Hoag S, Shaughnessy J.
Naval Hospital Jacksonville, Jacksonville, Florida, USA. anthonyjviera@yahoo.com
Irritable bowel syndrome is the most common functional disorder
of the gastrointestinal tract and is frequently treated by family
physicians. Despite patients' worries about the symptoms of irritable
bowel syndrome, it is a benign condition. The diagnosis should
be made using standard criteria after red flags that may signify
organic disease have been ruled out. An effective physician-patient
relationship is vital to successful management. Episodes of diarrhea
are best managed with loperamide, while constipation often will
respond to fiber supplements. Antispasmodics or anticholinergic
agents may help relieve the abdominal pain of irritable bowel
syndrome. Refractory cases are often treated with tricyclic antidepressants.
Newer agents such as tegaserod and ondansetron target neurotransmitter
receptors in the gastrointestinal tract Some forms of psychologic
treatment may be helpful, and gastroenterology consultation is
occasionally needed to reassure the patient. Comorbid conditions
such as depression or anxiety should be investigated and treated.
-----
Eur J Gastroenterol Hepatol 2002 Dec;14(12):1331-8
Extended analysis of a double-blind, placebo-controlled,
15-week study with otilonium bromide in
irritable bowel syndrome.
Glende M, Morselli-Labate AM, Battaglia G, Evangelista S.
BACKGROUND/OBJECTIVE: In order to follow the most recent developments
and recommendations in trial methodology for drug evaluation in
patients with irritable bowel syndrome, we performed an extended
analysis of a large clinical trial from a previously published
study of otilonium bromide, using an assessment that integrates
the key symptoms of irritable bowel syndrome. MATERIALS AND METHODS:
A large-scale clinical trial with a double-blind, placebo-controlled,
parallel-group study design was conducted in 378 patients, treated
for 15 weeks with the recommended standard dose of 40 mg otilonium
bromide or placebo three times daily. The study was based on the
collection of 12 single efficacy endpoints. The new efficacy assessment
was based on the data reported by the patients. Rather than demonstrating
score differences between the treatment groups of the study, we
carried out an assessment that integrates the most frequent symptoms
reported (pain frequency and intensity, presence of meteorism
and distension) by the patient. RESULTS: The rate of response
to treatment within 2-4 months (the primary efficacy outcome measure)
was significantly higher in the otilonium bromide group (36.9%)
than in the placebo group (22.5%; P = 0.007). In each month of
treatment, the rate of monthly response was higher in the otilonium
bromide group as compared to the placebo group (P < 0.05).
The total monthly and weekly responses to the single endpoints
(intensity and frequency of pain and discomfort, meteorism/abdominal
distension, severity of diarrhoea or constipation and mucus in
the stool) were significantly more frequent in the group treated
with otilonium bromide than in the placebo-treated group, with
differences ranging from 10% to 20%. The subgroup analysis of
the intestinal habits endpoint indicates that patients with diarrhoea
have an additional benefit. CONCLUSION: The present re-evaluation
of a previously published study confirms that otilonium bromide
is more effective than placebo for the treatment of irritable
bowel syndrome, being very efficient in relieving pain and discomfort.
-----
Dig Dis Sci 2002 Nov;47(11):2615-20
Effect of Lactobacillus plantarum 299v on colonic
fermentation and symptoms of
irritable bowel syndrome.
Sen S, Mullan MM, Parker TJ, Woolner JT, Tarry SA, Hunter JO.
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge,
UK.
A number of recent clinical trials have promoted the use of
probiotic bacteria as a treatment for irritable bowel syndrome
(IBS). The recent demonstration of abnormal colonic fermentation
in some patients with this condition provides an opportunity for
the objective assessment of the therapeutic value of these bacteria.
This study was designed to investigate the effects of Lactobacillus
plantarum 299V on colonic fermentation. We conducted a double-blind,
placebo-controlled, cross-over, four-week trial of Lactobacillus
plantarum 299V in 12 previously untreated patients with IBS. Symptoms
were assessed daily by a validated composite score and fermentation
by 24-hr indirect calorimetry in a 1.4-m3 canopy followed by breath
hydrogen determination for 3 hr after 20 ml of lactulose. On placebo,
the median symptom score was 8.5 [6.25-11.25 interquartile range
(IQR)], the median maximum rate of gas production was 0.55 ml/min
(0.4-1.1 IQR), and the median hydrogen production was 189.7 ml/24
hr (118.3-291.1 IQR). On Lactobacillus plantarum 299V the median
symptom score was 8 (6.75-13.5 IQR), the median maximum rate of
gas production 0.92 ml/min (0.45-1.5 IQR), and the median hydrogen
production 208.2 ml/24 hr (146-350.9 IQR). There was no significant
difference. Breath hydrogen excretion after lactulose was reduced
by the probiotic (median at 120 min, 6 ppm; placebo, 17 ppm; P
= 0.019). In conclusion, Lactobacillus plantarum 299V in this
study did not appear to alter colonic fermentation or improve
symptoms in patients with the irritable bowel syndrome.
-----
Dig Dis Sci 2002 Nov;47(11):2605-14
Hypnosis treatment for severe irritable bowel
syndrome: investigation of mechanism and
effects on symptoms.
Palsson OS, Turner MJ, Johnson DA, Burnelt CK, Whitehead WE.
University of North Carolina at Chapel Hill, Chapel Hill, North
Carolina 27599-7080 USA.
Hypnosis improves irritable bowel syndrome (IBS), but the mechanism
is unknown. Possible physiological and psychological mechanisms
were investigated in two studies. Patients with severe irritable
bowel syndrome received seven biweekly hypnosis sessions and used
hypnosis audiotapes at home. Rectal pain thresholds and smooth
muscle tone were measured with a barostat before and after treatment
in 18 patients (study I), and treatment changes in heart rate,
blood pressure, skin conductance, finger temperature, and forehead
electromyographic activity were assessed in 24 patients (study
II). Somatization, anxiety, and depression were also measured.
All central IBS symptoms improved substantially from treatment
in both studies. Rectal pain thresholds, rectal smooth muscle
tone, and autonomic functioning (except sweat gland reactivity)
were unaffected by hypnosis treatment. However, somatization and
psychological distress showed large decreases. In conclusion,
hypnosis improves IBS symptoms through reductions in psychological
distress and somatization. Improvements were unrelated to changes
in the physiological parameters measured.
-----
Adv Ther 2002 Sep-Oct;19(5):245-52
Charcoal tablets in the treatment of patients
with irritable bowel syndrome.
Hubner WD, Moser EH.
Berolina Drug Development GmbH, Neuenhagen, Germany.
This double-blind, randomized, multicenter, prospective clinical
trial evaluated a commercial formulation of charcoal tablets (Eucarbon)
and tablets containing only nonactivated charcoal (carbo ligni
[CL]) in 284 patients between the ages of 19 and 70 years with
irritable bowel syndrome (IBS). After 12 weeks, 262 patients were
available for intention-to-treat analysis. Overall well-being,
the primary efficacy parameter, was determined by means of the
Francis scoring system. Eucarbon treatment alleviated symptoms
by about 60%, but the relative gain in efficacy vis-a-vis the
CL group was only 9%. Several clinical observations and subgroup
analyses, however (eg, in patients suffering from constipation),
showed that Eucarbon was more effective. Both treatments were
well tolerated and produced adverse events at a similar frequency
(22%, Eucarbon vs 17%, CL). In most cases, it was not possible
to distinguish the adverse event from symptoms of IBS. The herbal
preparation Eucarbon was effective and safe in IBS, a complex
disease requiring long-term treatment.
-----
Psychosomatics 2002 Nov-Dec;43(6):451-5
Does a preexisting anxiety disorder predict response
to paroxetine in irritable bowel syndrome?
Masand PS, Gupta S, Schwartz TL, Kaplan D, Virk S, Hameed A, Lockwood
K.
Department of Psychiatry, Duke University Medical Center, Durham,
NC 27710, USA. masan001@mc.duke.edu
Irritable bowel syndrome (IBS) is the most common disorder
in patients seen by gastroenterologists. Twenty subjects with
IBS diagnosed with the Rome criteria were treated for 12 weeks
with 20-40 mg/day of paroxetine (mean dose=31 mg/day). At baseline,
10 patients had a lifetime history of an anxiety disorder, and
10 patients did not have such a history. Both groups had similar
improvement in abdominal pain, constipation, diarrhea, incomplete
emptying, and bloating/ abdominal distension. Paroxetine was very
well tolerated.
-----
Clin Pharmacokinet 2002;41(13):1021-42
Clinical pharmacokinetics of tegaserod, a serotonin
5-HT(4) receptor partial agonist with
promotile activity.
Appel-Dingemanse S.
Department of Clinical Pharmacology, Novartis Pharma AG, Basel,
Switzerland. silke.appeldingemanse@pharma.novartis.com
Tegaserod, a selective serotonin (5-hydroxytryptamine; 5-HT)
5-HT(4) receptor partial agonist, is indicated in patients with
irritable bowel syndrome (IBS) who identify abdominal pain or
discomfort and constipation as their predominant symptoms. Tegaserod
at dosages of 1 to 12 mg/day exerts pharmacodynamic actions in
the upper and the lower gastrointestinal tract, accelerating small
bowel and colonic transit in patients with IBS. Tegaserod is rapidly
absorbed following oral administration; peak plasma concentrations
(C(max)) are reached after approximately 1 hour. Absolute bioavailability
is about 10% under fasted conditions. Food reduces the bioavailability
of tegaserod by 40 to 65% and the C(max) by 20 to 40%. Systemic
exposure to tegaserod is not significantly altered at neutral
gastric pH compared with the fasted state (pH 2). Tegaserod is
approximately 98% bound to plasma proteins, primarily to alpha(1)-acid
glycoprotein, and has a volume of distribution at steady-state
of 368 +/- 223L. Tegaserod is metabolised mainly via two pathways.
The first is a presystemic acid-catalysed hydrolysis in the stomach
followed by oxidation and conjugation which produces the main
metabolite of tegaserod, 5-methoxyindole-3-carboxylic acid glucuronide
(M 29.0). This metabolite has negligible affinity for 5-HT(4)
receptors and is devoid of promotile activity. The second is direct
glucuronidation which leads to generation of three isomeric N-glucuronides.
The plasma clearance of tegaserod is 77 +/- 15 L/h, with an estimated
terminal half-life of 11 +/- 5 hours following intravenous administration.
Approximately two-thirds of the orally administered dose of tegaserod
is excreted unchanged in faeces, with the remainder excreted in
urine, primarily as M 29.0. The pharmacokinetics of tegaserod
are dose-proportional over the range 2 to 12mg given twice daily
for 5 days, with no relevant accumulation. The pharmacokinetics
of tegaserod in patients with IBS are comparable to those in healthy
individuals, and similar between men and women. No dosage adjustment
is required in elderly patients or those with mild to moderate
hepatic or renal impairment. Tegaserod should not be used in patients
with severe hepatic or renal impairment. No clinically relevant
drug-drug interactions with tegaserod have been identified. In
vivo drug-drug interaction studies with theophylline [a cytochrome
P450 (CYP) 1A2 prototype substrate], dextromethorphan (a CYP2D6
prototype substrate), digoxin, warfarin and oral contraceptives
have indicated no clinically relevant interactions and no requirement
for dosage adjustment.
-----
Aliment Pharmacol Ther 2002 Nov;16(11):1877-88
A randomized, double-blind, placebo-controlled
trial of tegaserod in female patients suffering from irritable
bowel syndrome with constipation.
Novick J, Miner P, Krause R, Glebas K, Bliesath H, Ligozio G,
Ruegg P, Lefkowitz M.
Charles City Research, Towson, MD, USA.
BACKGROUND: Irritable bowel syndrome is a common functional
gastrointestinal disorder which affects up to 20% of the population,
with a predominance in females. AIM: To evaluate the efficacy
and safety of tegaserod in female patients with irritable bowel
syndrome characterized by symptoms of abdominal pain/discomfort
and constipation. METHODS: In a randomized, double-blind, multicentre
study, 1519 women received either tegaserod, 6 mg b.d. (n = 767),
or placebo (n = 752) for 12 weeks, preceded by a 4-week baseline
period without treatment and followed by a 4-week open withdrawal
period. The primary efficacy evaluation was the patient's symptomatic
response as measured by the Subject's Global Assessment of Relief.
Other efficacy variables included abdominal pain/discomfort, bowel
habits and bloating. RESULTS: Tegaserod produced significant (P
< 0.05) improvements in the Subject's Global Assessment of
Relief and other efficacy variables. These improvements were seen
within the first week, and were maintained throughout the treatment
period. After withdrawal of treatment, the symptoms rapidly returned.
Overall, tegaserod was well tolerated. Diarrhoea was the most
frequent adverse event; however, this led to discontinuation in
only 1.6% of tegaserod-treated patients. CONCLUSIONS: Tegaserod,
6 mg b.d., produced rapid and sustained improvement of symptoms
in female irritable bowel syndrome patients and was well tolerated.
-----
Int J Colorectal Dis 2002 Nov;17(6):402-11
Improvement in irritable bowel syndrome following
ano-rectal surgery.
Palmer BV, Lockley WJ, Palmer RB, Kulinskaya E.
Lister Hospital, Corey's Mill Lane, Stevenage, SG1 4AB, UK. bernardpalmer@ntlworld.com
BACKGROUND AND AIMS: To assess the effect on irritable bowel
syndrome (IBS) of treating ano-rectal problems by applying multiple
Barron's bands to prolapsing mucosa and excising haemorrhoids,
with or without a low lateral sphincterotomy. PATIENTS AND METHODS:
144 patients with IBS whose ano-rectal abnormalities were treated
by a single consultant surgeon. A prospective "within person"
study of consecutive patients referred with ano-rectal problems
who also had IBS symptoms according to the Rome criteria. All
patients completed structured questionnaires about anal and IBS
symptoms before operation and 6-60 months later. The findings
were compared with those from patients who had no abdominal pains.
RESULTS: The principal IBS symptoms of abdominal pain, abdominal
distension, and altered bowel habit all improved significantly
after operation. Those with persistent anal problems had more
problems with persistent IBS symptoms, but when the anal problems
were corrected, the IBS tended to settle. Posterior anal tenderness
is present in 80% of IBS patients and is a useful diagnostic sign.
CONCLUSIONS: This work suggests that in many patients with IBS
there is a physical ano-rectal disorder amenable to physical treatment.
Patients with IBS should all be proctoscoped carefully, with and
without the patient straining, looking for abnormalities. Correcting
mucosal prolapse and other anal problems produced an improvement
in IBS symptoms in 86% of patients. This suggests that ano-enteric
reflexes are a significant factor in irritable bowel syndrome,
if not the major cause.
-----
Aliment Pharmacol Ther 2002 Oct;16(10):1701-8
Long-term safety of tegaserod in patients with
constipation-predominant irritable bowel syndrome.
Tougas G, Snape WJ Jr, Otten MH, Earnest DL, Langaker KE, Pruitt
RE, Pecher E, Nault B, Rojavin MA.
Medicine and Gastroenterology, McMaster University Medical Center,
Hamilton, Canada.
BACKGROUND: Tegaserod is a 5-hydroxytryptamine-4 receptor partial
agonist. Oral administration causes gastrointestinal effects resulting
in increased gastrointestinal motility and attenuation of visceral
sensation. AIM: : To determine the long-term safety and tolerability
of tegaserod in patients suffering from irritable bowel syndrome
with constipation as the predominant symptom of altered bowel
habits. METHOD: A multicentre, open-label study with flexible
dose titration of tegaserod in out-patients suffering from constipation-predominant
irritable bowel syndrome. RESULTS: A total of 579 patients with
constipation-predominant irritable bowel syndrome were treated
with tegaserod. Of these, 304 (53%) completed the trial. The most
common adverse events, classified as related to tegaserod for
any dose, were mild and transient diarrhoea (10.1%), headache
(8.3%), abdominal pain (7.4%) and flatulence (5.5%). Forty serious
adverse events were reported in 25 patients (4.4% of patients)
leading to discontinuation in six patients. There was one serious
adverse event, acute abdominal pain, classified as possibly related
to tegaserod. There were no consistent differences in adverse
events between patients previously exposed to tegaserod and those
treated de novo. No pattern-forming tegaserod-related abnormalities
in haematological and biochemical laboratory tests, urinalysis,
blood pressure, pulse rate or electrocardiograms were found. CONCLUSIONS:
Tegaserod appears to be well tolerated in the treatment of patients
with constipation-predominant irritable bowel syndrome. The adverse
event profile, clinical laboratory evaluations, vital signs and
electrocardiogram recordings revealed no evidence of any unexpected
adverse events, and suggest that treatment is safe over a 12-month
period.
-----
Curr Gastroenterol Rep 2002 Oct;4(5):427-34
New developments in the diagnosis and treatment
of irritable bowel syndrome.
Longstreth GF, Drossman DA.
Department of Gastroenterology, Kaiser Permanente Medical Care
Program, 4647 Zion Avenue, San Diego, CA 92120, USA. George.F.Longstreth@kp.org
Irritable bowel syndrome (IBS) is a common disorder with major
health status and economic effects. Symptom criteria are of paramount
importance in diagnosis, but differences among the Manning, Rome
I, and Rome II criteria may lead to variable identification of
people with the disorder. Practice guidelines are based on evidence
and, to a greater degree, on consensus; therefore, experts vary
on the specifics of ordering particular diagnostic tests. There
is an overlap of IBS symptoms with those of celiac sprue, and
selected patients should be tested for the latter disease. Symptom
confusion with biliary pain and overlap with chronic pelvic pain
could contribute to the predisposition of IBS patients to undergo
cholecystectomy and hysterectomy. Development and documentation
of effective therapy has been difficult, but depending on the
selection of subgroups, there is evidence for usefulness of smooth
muscle relaxants, loperamide, and antidepressants. Various forms
of psychological therapy and new serotonin-modulating agents seem
especially promising. The placebo effect of the physician-patient
relationship has important therapeutic benefit.
-----
Aliment Pharmacol Ther 2002 Sep;16(9):1649-54
Naloxone treatment for irritable bowel syndrome--a
randomized controlled trial with an oral formulation.
Hawkes ND, Rhodes J, Evans BK, Rhodes P, Hawthorne AB, Thomas
GA.
Department of Gastroenterology, Prince Charles Hospital, Merthyr
Tydfil, UK. NeilHawkes@aol.com
BACKGROUND: Opioids change gut motility and secretion, causing
delayed intestinal transit and constipation. Endorphins play a
role in the constipation troubling some patients with irritable
bowel syndrome; hence naloxone, an opioid antagonist, may have
a therapeutic role. AIM: To assess the efficacy and safety of
an oral formulation of naloxone in irritable bowel syndrome patients
with constipation. METHODS: A randomized, double-blind, placebo-controlled
trial was performed. Patients fulfilling the Rome II criteria
for irritable bowel syndrome (constipation-predominant and alternating
types) were randomized to receive 8 weeks of treatment with naloxone
capsules, 10 mg twice daily, or identical placebo. RESULTS: Twenty-eight
patients entered the study, which was completed by 25. 'Adequate
symptomatic relief' was recorded in six of 14 on naloxone and
three of 11 on placebo. Whilst the differences were not significant,
improvements in severity gradings and mean symptom scores for
pain, bloating, straining and urgency to defecate were greater
with naloxone than placebo for all parameters. In addition, quality
of life assessments improved to a greater extent in patients taking
naloxone. CONCLUSIONS: Preliminary results suggest that naloxone
is well tolerated and beneficial in patients with irritable bowel
syndrome and constipation. A larger clinical trial is needed to
provide sufficient statistical power to assess efficacy.
-----
J Clin Gastroenterol 2002 Jul;35(1 Suppl):S58-67
Irritable bowel syndrome neuropharmacology. A
review of approved and investigational compounds.
Callahan MJ.
Department of Medical Affairs, Novartis Pharmaceuticals Inc.,
59 Route 10, East Hanover, NJ 07936, USA.
Anticholinergics and prokinetics are mainstays of therapy for
Irritable Bowel Syndrome (IBS) patients despite their limited
efficacy and troublesome side-effect profile. The clinical limitations
of these drugs are a result of their relative broad and nonspecific
pharmacologic interaction with various receptors. Recent advances
in gut physiology have led to the identification of various receptor
targets that may play a pivotal role in the pathogenesis of IBS.
Medicinal chemists searching for safe and effective IBS therapies
are now developing compounds targeting many of these specific
receptors. The latest generation of anticholinergics, such as
zamifenacin, darifenacin, and YM-905, provide selective antagonism
of the muscarinic type-3 receptor. Tegaserod, a selective 5-HT4
partial agonist, tested in multiple clinical trials, is effective
in reducing the symptoms of abdominal pain, bloating, and constipation.
Ezlopitant and nepadudant, selective antagonists for neurokinin
receptors type 1 and type 2, respectively, show promise in reducing
gut motility and pain. Loperamide, a mu (mu) opioid receptor agonist,
is safe and effective for IBS patients with diarrhea (IBS-D) as
the predominant bowel syndrome. Fedotozine, a kappa (kappa) opioid
receptor agonist, has been tried as a visccral analgesic in various
clinical trials with conflicting results. Alosetron, a 5-HT3 receptor
antagonist, has demonstrated efficacy in IBS-D patients but incidents
of ischemic colitis seen in post-marketing follow-up resulted
its removal from the market. Compounds that target cholecystokinin.
A, N-methyl-D-aspartate, alpha 2-adrenergic, and corticotropin-releasing
factor receptors are also examined in this review.
-----
J Clin Gastroenterol 2002 Jul;35(1 Suppl):S53-7
Psychotropic agents in irritable bowel syndrome.
Wald A.
University of Pittsburgh Medical Center, Division of Gastroenterology,
Hepatology & Nutrition, PUH, Mezzanine Level, C-Wing, 200
Lothrop Street, Pittsburgh, PA 15213, USA. walda@msx.upmc.edu
The use of antidepressants to treat patients with irritable
bowel syndrome (IBS) has been extended in recent years because
of their possible neuromodulatory and analgesic effects, generally
in doses that do not have antidepressant effects. There seems
to be sufficient evidence to support the recommendation that psychotropic
agents may be effective in two clinical scenarios that are not
mutually exclusive. The first is in patients with IBS who have
pain and related symptoms that are unresponsive to medical therapy.
The second is in patients with IBS who have concomitant psychologic
dysfunction. This article reviews the evidence to support these
recommendations and guidelines, which may be used to optimize
medical management in these patients.
-----
J Clin Gastroenterol 2002 Jul;35(1 Suppl):S45-52
Diet in the irritable bowel syndrome.
Floch MH, Narayan R.
Gastroenterology & Nutrition Section, Norwalk Hospital, Yale
University School of Medicine, Norwalk, Connecticut, USA. martinfloch@snet.net
Patients with irritable bowel syndrome (IBS) often request
dietary recommendations. They must eat, and they want to know
what to eat. Present national guidelines recommend dietary treatment
with fiber for IBS patients with constipation. Diet recommendations
are made based on symptoms. There may be different dietary recommendations
for constipation, diarrhea, and pain or bloating. This article
reviews the relationship of foods to IBS and issues of food intolerances
and hypersensitivities, and recommendations for diet therapy.
The role of dietary fiber, both soluble and insoluble, is reviewed.
Although there are few studies to substantiate exact diets, broad
dietary plans are recommended for the different symptoms of IBS.
In addition, the recent literature on probiotics and prebiotics
pertinent to IBS is reviewed.
-----
Aliment Pharmacol Ther 2002 Aug;16(8):1407-30
Clinical perspectives, mechanisms, diagnosis and
management of irritable bowel syndrome.
Camilleri M, Heading RC, Thompson WG.
Mayo Clinic, Rochesster, MN 55905, USA. camilleri.michael@mayo.edu
This consensus document reviews the current status of the epidemiology,
social impact, patient quality of life, pathophysiology, diagnosis
and treatment of irritable bowel syndrome. Current evidence suggests
that two major mechanisms may interact in irritable bowel syndrome:
altered gastrointestinal motility and increased sensitivity of
the intestine. However, other factors, such as psychosocial factors,
intake of food and prior infection, may contribute to its development.
Management of patients is based on a positive diagnosis of the
symptom complex, careful history and physical examination to exclude
'red flags' as risk factors for organic disease, and, if indicated,
investigations to exclude other disorders. Therapeutic choices
include dietary fibre for constipation, opioid agents for diarrhoea
and low-dose antidepressants or infrequent use of antispasmodics
for pain, although the evidence basis for efficacy is limited
or in some cases absent. Psychotherapy and hypnotherapy are the
subject of ongoing study. Treatment should be tailored to patient
needs and fears. Novel therapies are emerging, and drugs acting
on serotonin receptors have proven efficacy and a scientific rationale
and, if approved, should be useful in the overall management of
patients with irritable bowel syndrome. Patient and physician
education, early identification of psychosocial issues and better
therapies are important strategies to reduce the suffering and
societal cost of irritable bowel syndrome.
-----
Aliment Pharmacol Ther 2002 Aug;16(8):1395-406
The treatment of irritable bowel syndrome.
Thompson WG.
University of Ottawa, Ottawa, Ontario, Canada. wgthomson@rogers.com
The efforts of clinical researchers, lay organizations and
pharmaceutical companies have increased the public profile of
irritable bowel syndrome and made it a respectable diagnosis.
Diagnostic symptom criteria encourage a firm clinical diagnosis,
which is the foundation of a logical management strategy. This
begins with education. Reassurance that no structural disease
threatens should be tempered with the reality that symptoms are
likely to recur over many years. Patients expect diet and lifestyle
advice, even if this is not specific to irritable bowel syndrome.
Only a few of those with irritable bowel syndrome see doctors,
and even fewer see specialists. Therefore, the treating physician
should ascertain the reason for the visit, the patient's fears
and the presence of any comorbid illness, such as depression,
that might require treatment in its own right. No drug treatment
is useful for all of the symptoms of irritable bowel syndrome,
and many patients require no drug at all. If used, drugs should
target the predominant symptom. Alosetron, a 5-HT3 antagonist,
is effective in treating women with irritable bowel syndrome who
also have diarrhoea. Tegaserod, a 5-HT4 agonist, is useful for
women with irritable bowel syndrome who are constipated. Most
patients with irritable bowel syndrome need psychological support.
Reassurance, discussion and relaxation techniques can be provided
by the family doctor. Difficult psychopathology may require referral
to a mental health professional, and the gastroenterologist can
settle diagnostic uncertainties. In all cases, successful treatment
depends on a confident diagnosis and the strength of the doctor-patient
relationship.
-----
Expert Opin Pharmacother 2002 Aug;3(8):1211-8
Tegaserod: a new 5-HT(4) agonist in the treatment
of irritable bowel syndrome.
Corsetti M, Tack J.
Department of Internal Medicine, Division of Gastroenterology,
University Hospital Gasthuisberg, University of Leuven, Belgium.
Tegaserod is a selective partial agonist acting on serotonergic
type 4 receptors (5-HT(4)). Pharmacodynamic studies indicate that
tegaserod is able to stimulate gut propulsion and secretion with
a net prokinetic effect. In contrast to other 5-HT(4) agonists
endowed with a complex pharmacological profile, tegaserod has
a reliable prokinetic activity in the colon. Clinical trials show
that tegaserod is effective and safe in the treatment of patients
with irritable bowel syndrome. In particular, tegaserod relieves
symptoms of abdominal pain, discomfort, abdominal bloating and
constipation.
-----
Aliment Pharmacol Ther 2002 Jul;16(7):1357-66
The effect of the 5-HT3 receptor antagonist, alosetron,
on brain responses to visceral stimulation in irritable bowel
syndrome patients.
Mayer EA, Berman S, Derbyshire SW, Suyenobu B, Chang L, Fitzgerald
L, Mandelkern M, Hamm L, Vogt B, Naliboff BD.
CURE Digestive Diseases Research Center / Neuroenteric Disease
Program, Department of Medicine, University of California School
of Medicine, Los Angeles, CA 90073, USA. emayer@ucla.edu
AIM: To conduct a placebo-controlled functional brain imaging
study to assess the effect of the 5-hydroxytryptamine-3 receptor
antagonist, alosetron, on irritable bowel syndrome symptoms, regional
brain activation by rectosigmoid distension and associated perceptual
and emotional responses. METHODS: Fifty-two non-constipated irritable
bowel syndrome patients (28 female) were enrolled in a randomized,
placebo-controlled trial with alosetron (1-4 mg b.d.). Thirty-seven
patients completed both brain scans following randomization. Rectosigmoid
stimulation was performed with a computer-controlled barostat.
Changes in regional cerebral blood flow were assessed using H215O
positron emission tomography. Stimulus ratings and changes in
gastrointestinal symptoms were assessed using verbal descriptor
scales. RESULTS: Alosetron, but not placebo, treatment was associated
with a decrease in symptom ratings, and reductions in emotional
stimulus ratings. Compared to baseline, alosetron treatment was
associated with reduced regional cerebral blood flow in bilateral
frontotemporal and various limbic structures, including the amygdala.
Compared to placebo, decreases in activity of the amygdala, ventral
striatum, hypothalamus and infragenual cingulate gyrus were significantly
greater after alosetron. CONCLUSIONS: In non-constipated irritable
bowel syndrome patients, 3 weeks of treatment with a 5-hydroxytryptamine-3
receptor antagonist decreases brain activity in response to unanticipated,
anticipated and delivered aversive rectal stimuli in structures
of the emotional motor system, and this is associated with a decrease
in gastrointestinal symptoms.
©Copyright 1992-date by The Center
for Current Research. The Irritable Bowel Syndrome File is a proprietary
compilation of the Center for Current Research. The information
in the File is solely for your use, and the use of your family,
friends, and doctors. The information is the property of the individual
researchers and institutions that produced it. It is an infringement
of copyright law to attempt to "resell" the information
as it is presented here.
|
