Dysmotility-like Functional Dyspepsia Research Articles

Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study

Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life. Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.

Long-Term Tegaserod Treatment for Dysmotility-like Functional Dyspepsia: Results of Two Identical 1-year Cohort Studies

Functional dyspepsia (FD) is a chronic disorder that adversely affects health-related quality of life (HRQoL). Published information on its long-term management is minimal and treatment options are limited. The aim of this study was to evaluate safety, efficacy and HRQoL with tegaserod 6 mg twice daily over 1 year in women with FD who completed one of two 6-week, randomized, placebo-controlled, double-blind studies. About 780 patients received tegaserod 6 mg twice daily in two identical 1-year extension studies. Scheduled assessments included adverse events, the Short-Form Nepean Dyspepsia Index (SF-NDI), Work Productivity and Activity Impairment-Dyspepsia (WPAI-Dyspepsia) questionnaire, and patient perceptions of treatment efficacy. Mean tegaserod treatment duration in the two studies was 236 and 222 days. Most adverse events occurred in the first 6 months, were similar to previous reports (commonly diarrhea), and were transient and well tolerated. SF-NDI, WPAI-Dyspepsia scores and perceived symptom relief improved from baseline over the 1-year evaluation. The long-term safety profile of tegaserod in women with FD was consistent with that of short-term treatment and accompanied by improvements in HRQoL, work productivity and symptom relief. These long-term results add to the clinical experience with FD and support the potential value of a 5-HT(4) agonist in the management of FD.

Plasma Ghrelin Levels and Their Relationship with Gastric Emptying in Patients with Dysmotility-Like Functional Dyspepsia

Background/Aims: Ghrelin affects gastric motility. However, little is known about the role of ghrelin in the pathophysiology of functional dyspepsia (FD). We investigated plasma ghrelin levels and their relationship with gastric emptying time in dysmotility-like FD patients. Methods: 42 patients with dysmotility-like FD and 14 healthy volunteers were enrolled in the study. Gastric half-emptying time was measured using a radiolabeled meal. Plasma total ghrelin levels before and after the meal were determined using a radioimmunoassay kit. Results: Preprandial ghrelin levels were significantly lower in FD patients than in controls. Postprandial ghrelin levels were similar between the two groups. Abnormally low preprandial ghrelin levels were observed in 7 out of 42 patients, in whom significant postprandial decrease of ghrelin levels was absent. Delayed gastric emptying was observed in 5 out of 7 patients with abnormally low ghrelin levels. Pre- or postprandial ghrelin levels were not significantly correlated with gastric half-emptying time, both in the patient group and in the control group. Conclusions: Abnormally low preprandial ghrelin levels and absence of significant postprandial decrease of ghrelin levels are present in a subset of dysmotility-like FD patients. Further investigation on the pathogenetic implication of these alterations in FD is required.

Tegaserod Treatment for Dysmotility-Like Functional Dyspepsia: Results of Two Randomized, Controlled Trials

Therapies for dysmotility-like functional dyspepsia (FD) are limited. We studied tegaserod, a selective serotonin type 4 receptor agonist, in patients with FD. Two identical multicenter, double-blind, randomized, placebo-controlled trials enrolled women >/=18 yr with recurring mid-upper abdominal discomfort characterized by postprandial fullness, early satiety, and/or bloating. Patients were randomized to tegaserod 6 mg b.i.d. or placebo. Two patient-reported primary variables were assessed: percentage of days with satisfactory symptom relief, and symptom severity using the composite average daily severity score (CADSS). In total, 2,667 women were randomized with no differences between trials in terms of recruitment method, Helicobacter pylori status, heartburn, or medication use. Mean percentage of days with satisfactory symptom relief for tegaserod versus placebo in Trial 1: 32.2%versus 26.6% (95% CI of treatment difference 2.82, 9.27; P < 0.01), Trial 2: 31.9%versus 29.4% (95% CI of treatment difference -0.21, 6.53; P= 0.066). Mean CADSS in Trial 1: 3.14 versus 3.35 (95% CI of treatment difference -0.29, -0.10; P < 0.0001), Trial 2: 3.15 versus 3.23 (95% CI of treatment difference -0.18, 0.01; P= 0.094). Meta-analysis showed significant benefit for both end points: increase in days with satisfactory relief 4.6% (95% CI 2.29, 6.96); decrease in CADSS 0.14 (95% CI 0.21, 0.07). Treatment effect was greater in patients with severe baseline symptoms. Diarrhea requiring study discontinuation was more common with tegaserod than placebo (4.1%vs 0.3%). Some improvement in dysmotility-like FD was observed with tegaserod treatment. The clinical implication of this improvement is uncertain.

S1663 Enhanced Ghrelin Production and Secretion and Reduced Expression of Ghrelin Receptor in Rat Stomach with Delayed Gastric Emptying

Background. Ghrelin is a gastrointestinal peptide that stimulates growth hormone secretion, food intake, body weight gain and upper gastrointestinal motility. Ghrelin has distinct effects on gastrointestinal motility, which may be mediated through the growth hormone secretagogue receptor (GHS-R) on the vagus nerve and enteric nerve endings. We previously reported that plasma ghrelin levels were significantly higher in patients with dysmotilitylike functional dyspepsia (Aliment Pharmacol Ther. S4:104-110, 2006). Plasma ghrelin was also increased in obese patients after gastric banding operation (Obese Surg. 15, 1024-9, 2005). The aim of the present study was to investigate the influence of delayed gastric emptying caused by surgical manipulation on the dynamics of ghrelin and GHS expression in rats.Methods. 7-week-old male Sprague-Dawley rats with or without duodenal strictures were used as models of delayed gastric emptying. After 24 hours' fasting, the rats were divided into two groups, as follows; Control group (n=14; sham operation with abdominal incision alone), impaired gastric emptying group (n=14; proximal duodenal stricture with an 18 Fr.-Nelaton catheter) As weight loss is known to increase the circulating levels of ghrelin, a pair-feeding method was applied to equalize the body weight. Rats were sacrificed 2 weeks after the operation after the 24 hours' food deprivation. Gastric emptying rate was evaluated by the phenol red method. Plasma and gastric levels of ghrelin levels were measured by radioimmunoassay. Gastric expressions of preproghrelin mRNA and GHS-R mRNA were evaluated by quantitative RT-PCR, and immunohistochemistry was performed to determine gastric ghrelin localization. Results. No significant differences in the body weight were observed among two groups. The gastric emptying rate in groups with duodenal stricture was significantly lower compared with control group (9.8%, 61.0%, p<0.05). Rats with duodenal strictures showed significant increase in the preproghrelin mRNA expression (p<0.05) and density of ghrelin positive cells in the stomach (p<0.01), significant decrease of gastric total ghrelin levels (p<0.05), and increase of the plasma total ghrelin levels (p<0.01), while they showed a significant decrease in the levels of GHS-R mRNA expression (p<0.05). Conclusion. The present study has provided the first evidence that production and secretion of gastric ghrelin is enhanced in rats with delayed gastric emptying. It suggests that deregulation of gastric accommodation and emptying would induce the enhancement of ghrelin dynamics and the down-regulation of GHS-R.

Effectiveness and safety of levosulpiride in the treatment of dysmotility-like functional dyspepsia

The objective of this study was to assess the effectiveness and safety of levosulpiride in patients with dysmotility-like functional dyspepsia including nonerosive reflux esophagitis in conditions of daily practice. The study was conducted as a prospective, open-label, multicenter design in 342 patients with dysmotility-like functional dyspepsia (n=279) and nonerosive reflux disease (n=63), who received levosulpiride 25 mg 3 times daily orally for 4 weeks. Individual symptoms (pain/discomfort, fullness, bloating, early satiety, pyrosis, regurgitation, and nausea/vomiting) and a global symptom score were assessed at 15, 30, and 60 days after starting treatment. Adverse events also were recorded. There were 151 men and 191 women (mean age 38.8 years) who referred dyspeptic symptoms for a mean of 10.2 (10.7) months. A total of 66.4% patients were treated with 75 mg/day levosulpiride and 33.6% with 50 mg/day. At the 15-day visit, a decrease greater than 50% in the global symptom score was observed. The frequency and intensity of individual symptoms showed a statistically significant decrease (p<0.001) at all visits compared with baseline. At the 30-day visit, all symptoms had almost disappeared, a trend that was maintained until the last visit. Treatment with levosulpiride was well tolerated and only 40 adverse events were recorded (galactorrhea 26.7%, somnolence 17.8%, fatigue 11.1%, headache 11.5%) and no patient had to abandon the study due to side effects. In conclusion, levosulpiride is an effective and safe drug in the treatment of dysmotility-like functional dyspepsia and non-erosive reflux disease.

Improvement of gastrointestinal quality of life scores in cases of Helicobacter pylori‐positive functional dyspepsia after successful eradication therapy

Functional dyspepsia (FD) refers to a broad range of chronic upper abdominal symptoms associated with food intake. A definitive treatment for FD has not yet been established, and the effect of Helicobacter pylori (H. pylori) eradication still remains under debate. The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The present study examined the quality of life (QOL) of patients with H. pylori-positive FD following H. pylori eradication. Sixty-eight patients with FD who gave informed consent were recruited for the study. H. pylori infection was diagnosed by the culture and histological methods, and the H. pylori eradication consisted of a 7-day course of lansoprazole, amoxicillin and clarithromycin. The overall success of the treatment was confirmed by a 13C urea breath test (UBT) conducted 3 months after the eradication. The GSRS questionnaire was administered to the patient just before the start of the eradication therapy and at 3 months after the therapy, just before the UBT was performed. In successfully eradicated patients, the total GSRS and the abdominal pain score significantly decreased. In particular, the abdominal pain score and indigestion score were significantly decreased after successful eradication in patients with ulcer-like FD or dysmotility-like FD. Conversely, in patients in whom the eradication was unsuccessful, neither the total GSRS nor any of the individual symptom scores showed any significant change. Successful H. pylori eradication improved the QOL of patients with FD, in particular H. pylori-positive patients with ulcer-like FD or dysmotility-like FD.

Levosulpiride and cisapride in the treatment of dysmotility-like functional dyspepsia: a randomized, double-masked trial

Background & Aims: Levosulpiride is a benzamide derivate d 2 dopamine antagonist with prokinetic activity that can accelerate gastric emptying and reduce discomfort in response to gastric distention. The aim of the study is to compare the clinical efficacy of levosulpiride and cisapride in patients with dysmotility-like functional dyspepsia. Methods: In a exploratory pilot study performed as a multicenter, randomized, double-masked trial, the effects of 8 weeks of treatment with either levosulpiride, 25 mg, 3 times daily (n = 69) or cisapride, 10 mg, 3 times daily (n = 71) were compared. Individual symptoms (pain/discomfort, fullness, bloating, early satiety, and nausea/vomiting), global symptom score, effect on health-related quality of life (HRQoL), and anxiety-state and anxiety-trait were evaluated. Adverse events also were recorded. Results: Both levosulpiride and cisapride improved dyspeptic symptoms and decreased total symptom score (79.9% and 71.3%, respectively); no significant statistical difference between treatments was found ( P = 0.07 for total symptom score). HRQoL improved similarly after both treatments, whereas no change was observed in anxiety. Medication-related adverse effects were present in 13 of 69 patients (18.8%) in the levosulpiride group and 8 of 71 patients (11.3%) in the cisapride group. Significantly more ( P = 0.03) patients treated with cisapride had to abandon the trial because of side effects. Conclusions: Levosulpiride is at least as effective as cisapride in the treatment of dysmotility-like functional dyspepsia.

Postprandial symptoms in dysmotility-like functional dyspepsia are not related to disturbances of gastric myoelectrical activity.

Gastric dysrhythmias, such as tachy- or bradygastria, have been reported in patients with functional dyspepsia (FD), but their role in symptom production is uncertain. It is also not known whether gastric dysrhythmias in these patients can be elicited by physiological gastric distension with a meal. We investigated the relationships between symptoms after ingestion of different volumes of water following a test meal and gastric dysrhythmias in FD patients. Fourteen patients with dysmotility-like FD and 13 healthy volunteers underwent paired electrogastrography (EGG) studies. Fasted subjects ingested 150 ml of yoghurt with either 150 ml (low volume) or 300 ml (high volume) water in random order. Fasting and fed EGGs with monitoring of symptoms were performed in both studies. Ten FD patients (71.4%) reported upper abdominal discomfort and bloating after the low volume meal, but only one (7.1%) presented an abnormal EGG (dominant frequency in the 2-4-cpm range: 58%). Following the high volume meal, 7 patients (50%) had symptoms, but none had EGG abnormalities. No significant differences were found between FD patients and controls for any of the EGG variables, in any test. In FD patients with postprandial symptoms, the percentage of the EGG dominant frequency in the normal range (median, 84.6%; range, 76.0-100.0%) was similar (P>0.20) to that in those without symptoms (88.5%; 75.0-100.0%). We conclude that disturbances of gastric myoelectrical activity are unlikely to play a role in the origin of postprandial upper abdominal discomfort and bloating in dysmotility-like FD.

Levosulpiride in the treatment of dysmotility-like functional dyspepsia: Randomised double-dimmed comparison with cisapride

Levosulpiride in the treatment of dysmotility-like functional dyspepsia: Randomised double-dimmed comparison with cisapride

Orocecal transit time in patients with functional dyspepsia.

The importance of intestinal dysmotility in functional dyspepsia is a controversial issue. To investigate the orocecal transit time in patients with functional dyspepsia, as well as a possible association between intestinal transit and the presence of anxiety or Helicobacter pylori infection in these patients. The participants in this study were 23 patients with dysmotility-like functional dyspepsia and 24 control subjects. Orocecal transit time was measured by the lactulose hydrogen breath test. The presence of anxiety was assessed by the Hospital Anxiety and Depression (HAD) scale. No significant difference in orocecal transit times was found between patients (median, 55 minutes; 95% confidence interval [CI], 40-60 minutes) and control subjects (median, 50 minutes; 95% CI, 40-60 minutes; p = 1). In the assessment, 15 patients (73%) scored for anxiety on the HAD scale, and 15 patients (65%) had positive test results for H. pylori. There was no significant difference in orocecal transit times between the patients with (median, 55 minutes; 95% CI, 40-63 minutes) and those without H. pylori infection (50 minutes; 95% CI, 40-68 minutes; p = 0.85), or between the patients with (median, 45 minutes; 95% CI, 40-68 minutes) and those without (60 minutes; 95% CI, 40-63 minutes; p = 0.77) anxiety. Orocecal transit time is within the normal range in patients with functional dyspepsia. Anxiety and H. pylori infection do not seem to influence orocecal transit time in these patients.

Functional (Nonulcer) Dyspepsia.

Functional (nonulcer) dyspepsia refers to upper abdominal pain or discomfort with or without symptoms of early satiety, nausea, or vomiting with no definable organic cause. The current Rome II criteria help to diagnose functional dyspepsia and avoid misdiagnosis of gastroesophageal reflux disease and irritable bowel syndrome as functional dyspepsia. Assessment of gastric emptying with scintigraphy or breath testing may be useful in identifying delayed gastric emptying in patients with dyspeptic symptoms and may be helpful in patient management. Electrogastrography is a noninvasive test that evaluates for gastric dysrhythmias. Satiety testing is being evaluated as an indirect test for impaired fundic relaxation and visceral hypersensitivity. The symptom response to Helicobacter pylori therapy in patients with functional dyspepsia and a negative endoscopy examination but a positive H. pylori test is marginal. Lifestyle modifications often are suggested for initial treatment of functional dyspepsia. Dietary changes such as frequent small meals, low-fat diet, and avoidance of certain aggravating foods may improve symptoms. Additional measures include cessation of smoking, avoiding excess alcohol intake, and minimizing coffee intake. Antacids and over-the-counter histamine type 2 receptor antagonists may be helpful as an "on-demand" therapy for intermittent symptoms. They are safe and relatively inexpensive. Different subgroups of functional dyspepsia are based on the predominant symptom and may help in choosing an appropriate drug to initiate therapy. If the predominant symptom is epigastric pain (ulcer-like functional dyspepsia), histamine-2 receptor antagonists or proton pump inhibitors are the initial treatment of choice. If fullness, bloating, early satiety or nausea is the predominant complaint (dysmotility-like functional dyspepsia), a prokinetic agent may help. Metoclopramide is the only available effective prokinetic agent at present. If metoclopramide is used, short-term treatment and discussion of possible side effects with the patient are advised. If there is no response to these initial treatments, switching therapy from proton pump inhibitor to prokinetic or vice versa can be tried. If these treatment options fail, patient re-evaluation for other disorders (including other functional bowel disorders) is advised. A low-dose tricyclic antidepressant at bedtime may be helpful for treatment of visceral hypersensitivity.

Autonomic function in patients with functional dyspepsia assessed by 24-hour heart rate variability.

The function of the autonomic nervous system was assessed in 23 patients with dysmotility-like functional dyspepsia and 12 healthy volunteers by analysis of 24-hr heart rate variability and a battery of five standardized sympathetic and parasympathetic cardiovascular reflex tests. Measures of heart rate variability were obtained by analysis of ambulatory electrocardiographic recordings using both the time and the frequency domain methods. The values of parameters reflecting vagal activity (HF, rMSSD) were significantly lower in patients with functional dyspepsia. Individual analysis of heart rate variability data identified at least one abnormal parameter of vagal function in seven (30.4%) patients, and in five of these the results of parasympathetic cardiovascular reflex tests were also abnormal. Our results suggest impaired efferent vagal function in a subgroup of patients with functional dyspepsia. This abnormality may play a role in the pathogenesis of the disease in these patients.

Gastric myoelectrical and emptying activity in patients with gastroesophageal reflux disease and dysmotility-like functional dyspepsia (GERD+): effect of water load test

Gastric myoelectrical and emptying activity in patients with gastroesophageal reflux disease and dysmotility-like functional dyspepsia (GERD+): effect of water load test

Can symptoms discriminate among those with delayed or normal gastric emptying in dysmotility-like dyspepsia?

OBJECTIVE: Different subgroups can be identified in functional dyspepsia based on symptom type or severity, and may correlate with pathophysiological disturbances. In particular, female sex and severe fullness and vomiting have been reported to be strong independent predictors of slow solid gastric emptying. We aimed to determine if symptom patterns or severity could identify those with abnormal gastric emptying among patients with dysmotility-like functional dyspepsia and, for comparison, type I diabetes mellitus. METHODS: Patients with postprandial symptoms and documented functional dyspepsia by endoscopy (n = 551) and patients with type I diabetes who had postprandial dyspepsia (n = 247) enrolling in two separate randomized controlled trials were evaluated at baseline. Patients were assigned to either the delayed or normal gastric emptying strata, based on a validated C 13 octanoic acid breath test with sampling over 4 h. A self-report questionnaire measured the presence and severity of eight symptoms on visual analog scales. The validated Nepean Dyspepsia Index measured the frequency, severity, and bothersomeness of 15 upper GI symptoms on Likert scales. RESULTS: Gastric emptying was definitely delayed (t1/2 >192 min) in 24% of patients with functional dyspepsia and 28% with diabetes. Delayed gastric emptying was associated with female gender but not age or Helicobacter pylori status. The age- and sex-adjusted risk (odds ratio) of delayed gastric emptying for the upper GI symptoms ranged from 0.99 to 1.0 (all p values ≥0.2). The results were very similar in functional dyspepsia and diabetes. There was also no correlation between t1/2 and number of symptoms or symptom severity scores. CONCLUSION: Symptom prevalence and severity were similar in dyspeptic patients with and without delayed gastric emptying. Specific symptoms do not seem to be of predictive value in dysmotility-like dyspepsia for identifying alterations of gastric emptying.

1 Nomenclature of dyspepsia, dyspepsia subgroups and functional dyspepsia: Clarifying the concepts

There is international agreement that dyspepsia refers to pain or discomfort centred in the upper abdomen. However, the term ‘discomfort’ has been variably defined. While other symptoms may often be simultaneously present, gastro-oesophageal reflux disease can usually be clearly distinguished by the presence of predominant heartburn. Dyspepsia is a frequent reason for consultation in primary care and in gastrointestinal practice. With the widespread availability and utilization of endoscopy, it has become evident that a structural (or organic) explanation is found in only a minority of patients presenting with dyspepsia. Operationally, functional dyspepsia is defined as persistent or recurrent dyspepsia for 3 or more months in the absence of a clinically identifiable structural disease causing the symptoms. It has been proposed, based on symptoms, that functional dyspepsia be subdivided into symptom subgroups to promote patient homogeneity. The initially proposed ‘clustering’ of symptoms into ulcer-like and dysmotility-like functional dyspepsia has proved a dismal failure because of the considerable overlap observed, the lack of stability over time and the failure to identify robust pathophysiological abnormalities or responses to therapy. A subcategorization based upon the most bothersome symptom is theoretically more attractive but needs to be prospectively and rigorously tested.

Responses to gastric distension in functional dyspepsia

Background—Studies have shown that an altered visceral perception threshold plays a role in the pathogenesis of upper gastrointestinal tract symptoms in dyspeptic patients. However, it is not clear whether the...

Correlation between symptomatic improvement and parameters of gastric motility after erythromycin(EM) treatment in patients with dysmotility-like functional dyspepsia (FD)

Correlation between symptomatic improvement and parameters of gastric motility after erythromycin(EM) treatment in patients with dysmotility-like functional dyspepsia (FD)