Diarrhea-predominant Irritable Bowel Syndrome Patients Research Articles

A randomized, controlled exploratory study of clonidine in diarrhea-predominant irritable bowel syndrome

Background & Aims: The aim of this study was to evaluate the efficacy and tolerability of the alpha-2 adrenoreceptor agonist, clonidine, in patients with diarrhea-predominant irritable bowel syndrome (D-IBS) in a double-blind, randomized, parallel-group, placebo-controlled trial. Methods: A 2-week run-in evaluated baseline symptoms. Patients received 0.05, 0.1, or 0.2 mg clonidine or placebo twice a day for 4 weeks. We evaluated satisfactory relief of IBS by weekly question and stool parameters with a daily diary. Satisfactory relief and overall bowel function were primary end points. Secondary end points were stool frequency, consistency, and ease of passage; gut transit; and fasting and postprandial gastric volumes. Analysis followed intention-to-treat principles. Results: Forty-four D-IBS patients participated; there were 4 treatment-related dropouts: 2/2 in the 0.2-mg and 2/12 in the 0.05-mg clonidine groups. Proportion with satisfactory relief of IBS was 0.46, 0.42, and 0.67 with placebo, 0.05 mg, and 0.1 mg clonidine, respectively. Relief was sustained through 4 weeks of treatment, and bowel dysfunction (firmer stools and easier stool passage [ P < 0.05]) was reduced with clonidine, 0.1 mg twice a day. Clonidine did not significantly alter gastrointestinal transit or gastric volumes. Drowsiness, dizziness, and dry mouth were the most common adverse events with the 0.1-mg dose; severity of adverse effects subsided after the first week of treatment. A trial to replicate 20% or more responders with clonidine will require 95 patients per treatment arm. Conclusions: Clonidine, 0.1 mg twice a day for 4 weeks, relieves bowel dysfunction and appears promising for relief of D-IBS; these effects are unassociated with significant alterations in transit.

Gender-related differences in slowing colonic transit by a 5-HT 3 antagonist in subjects with diarrhea-predominant irritable bowel syndrome

OBJECTIVE: To evaluate the influence of gender on the effect of a 5-HT 3 antagonist, alosetron, 1 mg b.i.d., on GI and colonic transit in D-IBS. METHODS: Thirty patients (15 male, 15 female) with D-IBS received 1 mg b.i.d. alosetron for 6 wk. Transit was measured by scintigraphy at baseline and at the end of treatment. RESULTS: Alosetron, 1 mg b.i.d., significantly retarded small bowel and, proximal and overall colonic transit in the 30 patients with D-IBS. The effect of alosetron on the primary endpoint, colonic geometric center at 24 h, was significantly greater in females than in males ( p < 0.05). However, two females showed no slowing of colonic transit on treatment. Among male patients, two of 15 had a slowing of colonic transit at 24 h that was greater than the mean change in female patients, suggesting responsiveness to alosetron among a subgroup of males. CONCLUSION: A 5-HT 3 antagonist, alosetron, significantly retards small intestinal and colonic transit in diarrhea-predominant IBS patients, with significantly greater female to male responsiveness. Gender partly contributes to differences in the serotonergic control of intestinal and colonic transit in patients with D-IBS.

Rectal hypersensitivity may be play a role in diarrhea-predominant irritable bowel syndrome patients younger than 40 year-old or with normal parasympathetic function

Rectal hypersensitivity may be play a role in diarrhea-predominant irritable bowel syndrome patients younger than 40 year-old or with normal parasympathetic function

Rectal hypersensitivity may be play a role in diarrhea-predominant irritable bowel syndrome patients younger than 40 year-old or with normal parasympathetic function

Rectal hypersensitivity may be play a role in diarrhea-predominant irritable bowel syndrome patients younger than 40 year-old or with normal parasympathetic function

Effect of a calcium channel blocker and antispasmodic in diarrhoea‐predominant irritable bowel syndrome

Irritable bowel syndrome (IBS) is a colonic function disorder. Both pinaverlum bromide (a selective calcium channel blocker) and mebeverine (an antispasmodic) are reported to be effective in the long-term (12-16 weeks) treatment of IBS patients. Their efficacy in the short-term treatment of IBS patients and colonic transit time is unclear. Furthermore, substance P and neuropeptide Y have either excitatory or inhibitory effects on colonic motility. Whether the efficacy of both drugs is mediated through these neuropeptides remains unknown. A clinical trial was conducted with 91 patients with diarrhoea-predominant IBS. After basal measurement of the total colonic transit time, IBS patients were randomized to receive either pinaverlum bromide (50 mg, t.i.d.) or mebeverine (100 mg, t.i.d.) for 2 weeks. The symptomatic scores regarding defaecation, total colonic transit time and serum levels of substance P and neuropeptide Y were measured before and after treatments. The daily defaecation frequency was markedly decreased after treatment (pinaverlum bromide, 2.9+/-1.2 vs 2.0+/-1.0, P< 0.05; mebeverine, 2.7+/-1.1 vs 2.1+/-1.0, P< 0.05). The stool consistency became well formed after both treatments (P< 0.05). Both drugs similarly improved the global well-being in these IBS patients (pinaverlum bromide vs mebeverine 73.4 vs 71.8%, P> 0.05). The total colonic transit time was significantly prolonged only after pinaverlum bromide treatment (21.4+/-15.5 vs 30.8+/-14.8 h, P< 0.01). Neither substance P nor neuropeptide Y serum level was significantly changed after either treatments. Pinaverlum bromide and mebeverine have similar therapeutic efficacies on diarrhoea-predominant IBS patients. Prolonged colonic transit time may be one of the factors responsible for the efficacy of pinaverlum bromide on the IBS patients. Substance P and neuropeptideY appear less important in the pathogenesis of diarrhoea-predominant IBS.

Perceptual Hyperreactivity to Auditory Stimuli in Patients with Irritable Bowel Syndrome

Background: Patients with irritable bowel syndrome (IBS) have abnormal perception of visceral stimuli; however, no study has so far investigated the perception of non-visceral stimuli in IBS. In the present study we used event-related potentials (ERP) to study whether IBS patients differed from healthy controls in processing of auditory stimuli and, if so, how this was influenced by emotions. Methods: We compared ERPs to auditory stimuli in 40 female diarrhoea-predominant IBS patients without current psychiatric illness with those in 20 healthy controls. Tones were used as standard and target stimuli, and words with emotional content as distractors. Characteristics of the first negative wave (N100) and mean amplitudes in 50-msec time intervals between 150 and 600 msec were assessed. Results: At the frontal midline electrode IBS patients had significantly enhanced N100 amplitude to all stimuli, persisting after adjustment for age, current emotions, and personality traits. They additionally had enhanced waves 200-300 msec and 400-500 msec after stimulus. The latter differences disappeared after adjustment for emotions and personality traits. Conclusions: In the frontal brain region, IBS patients seem to have a hyperreactivity to auditory stimuli compared with controls. Later elements (P300, N400) of stimulus processing were influenced by emotions and personality traits. These may possibly contribute to changes in intestinal motility caused by stress. The study indicates that aberrant brain functioning may be an element of the irritable bowel syndrome. It may elucidate a mechanism for brain-gut interaction by which psychosocial stress may influence visceral pain perception in non-psychiatric subjects with an intestinal motility disorder and also the efficacy of psychiatric treatment on IBS symptoms.

Abnormal vagal cholinergic function and psychological behaviors in irritable bowel syndrome patients: a hospital-based Oriental study.

Irritable bowel syndrome (IBS) patients in Western countries usually manifest autonomic nerve dysfunctions and abnormal psychological behaviors. The purpose of this study was to assess whether Oriental IBS patients with predominant bowel symptoms also exhibited similar abnormalities. We enrolled 40 IBS patients from the outpatient clinic and 20 controls with normal daily bowel habit for study. The IBS patients were further divided according to their predominant bowel habit: 20 were constipation-predominant and 20 were diarrhea-predominant. Sympathetic function was evaluated by sympathetic skin response (SSR) while vagal cholinergic function was determined by measuring R-R interval variation (RRIV) in electrocardiography during rest and deep breathing. Psychological parameters were assessed by scales of the Minnesota Multiphasic Personality Inventory (MMPI) and the Hopkins Symptom Checklist (HSCL-90). IBS patients, despite their bowel habit, showed normal SSR response. RRIV during deep breathing was significantly lower in constipation-predominant IBS patients than in controls or diarrhea-predominant IBS patients (16.5+/-3.1% vs 20.5+/-4.8% and 21.5+/-4.6%, P < 0.001). IBS patients also exhibited abnormal MMPI measuring scores on depression, hysteria, paranoia, and masculinity/femininity scales. In addition, they also had more severe psychological distress in the items of HSCL-90 measurement. In conclusion, vagal dysfunction characterizes Oriental constipation-predominant IBS patients seeking medical help. Abnormal psychoneurotic profiles also exist in these IBS patients, irrespective of their bowel habits.

Fecal short-chain fatty acids in patients with diarrhea-predominant irritable bowel syndrome: in vitro studies of carbohydrate fermentation.

Colonic bacterial production of short-chain fatty acids (SCFA) plays an important role in the salvage of unabsorbed carbohydrate and in colonic absorption of electrolytes and water. The objective of this study was to determine whether patients with diarrhea-predominant irritable bowel syndrome (DP-IBS) have a different pattern and rate of fermentation of carbohydrate and fiber to SCFA compared with controls. Fecal homogenates from 10 patients with DP-IBS and 10 age-matched controls were studied. SCFA were measured by gas chromatography in baseline fecal samples and in fecal homogenates in an in vitro anaerobic fermentation system after incubation with no additional substrate, lactulose, potato starch, citrus pectin, and hemicellulose over a 24-hour period. Net SCFA production rates were calculated for the first 6 h of the incubation period. Patients with DP-IBS had a consistently different pattern of less total SCFA, a lower percentage of acetate (p < 0.05), and a higher proportion of n-butyrate (p < 0.05) than controls. In stool homogenates from both controls and DP-IBS patients, lactulose fermentation resulted in the highest rate of SCFA production followed by pectin, starch, and hemicellulose. However, at all time points, the fecal homogenates from controls generated a higher concentration of total SCFA, acetate, and propionate with all substrates tested. SCFA production rates were higher in controls incubated with lactulose, starch, and hemicellulose. The fecal SCFA profile of patients with DP-IBS is characterized by lower concentrations of total SCFA, acetate, and propionate and a higher concentration and percentage of n-butyrate. Fecal flora from these patients produced less SCFA in an in vitro fermentation system in response to incubations with various carbohydrates and fibers. Differences in SCFA production by colonic bacterial flora in patients with DP-IBS may be related to the development of gastrointestinal symptoms.

Influence of antidepressants on whole gut and orocaecal transit times in health and irritable bowel syndrome

Antidepressants are used in the treatment of irritable bowel syndrome but it is unclear whether any symptomatic improvement is due solely to correction of an associated affective disorder, or whether these drugs have effects on bowel function which may be of therapeutic benefit. Intestinal transit is known to be abnormal in some irritable bowel syndrome patients. We have studied the effects of imipramine, a tricyclic antidepressant with mixed pharmacological properties, and paroxetine, a selective 5-hydroxytryptamine re-uptake inhibitor, on intestinal transit times. Median (range) whole gut transit time was lower in 10 diarrhoea-predominant irritable bowel syndrome patients, 22.2 (3.6-51.6) h, compared to 28 control subjects 39.6 (7.2-68.4) h, (P < 0.05). Similarly, orocaecal transit time was shorter at 55 (30-90) min in diarrhoea-predominant irritable bowel syndrome patients compared to 75 (40-150) min in controls, (P < 0.05). Four days' administration of imipramine increasing to a daily dose of 100 mg prolonged both orocaecal and whole gut transit times in 12 control subjects and six diarrhoea-predominant irritable bowel syndrome patients. In contrast, 30 mg paroxetine daily for 4 days reduced orocaecal transit time in ten controls and eight irritable bowel syndrome patients, but had no effect on whole gut transit time. Short-term administration of antidepressants alters intestinal transit, but the selective 5-hydroxytryptamine re-uptake inhibitor, paroxetine, has different effects to the tricyclic drug, imipramine. These effects on transit precede any effects on mood. Although there is a high prevalence of affective disorder in irritable bowel syndrome clinic patients, these drugs may have additional therapeutic actions on the gut. These actions might be taken into account when prescribing antidepressants in irritable bowel syndrome.