Efficacy of Buspirone, a Fundus-Relaxing Drug, in Patients With Functional Dyspepsia

doi:10.1016/j.cgh.2012.06.036

Clinical Gastroenterology and Hepatology

Volume 10, Issue 11, November 2012, Pages 1239-1245

https://doi.org/10.1016/j.cgh.2012.06.036 Get rights and content

Background & Aims

Impaired accommodation and hypersensitivity to gastric distention are believed to be involved in the development of functional dyspepsia (FD). Buspirone, a 5-hydroxytryptamine 1A receptor agonist, relaxes the proximal stomach in healthy individuals. We studied the effects of buspirone on symptoms and mechanisms of FD.

Methods

We performed a randomized, double-blind, placebo-controlled, crossover study of 17 patients (13 women; mean age, 38.5 ± 2.4 years). The study included 2 treatment periods of 4 weeks each, separated by a 2-week washout period. In the first period, 7 participants were given buspirone (10 mg, 3 times daily for 4 weeks) and 10 were given placebo 15 minutes before meals; patients switched groups for the second period. We assessed meal-related symptoms and severity, along with gastric sensitivity, accommodation, and emptying (by using barostat and breath tests) before and after 4 weeks of treatment.

Results

Buspirone significantly reduced the overall severity of symptoms of dyspepsia (7.5 ± 1.3 vs 11.5 ± 1.2 for placebo; P < .005) and individual symptoms of postprandial fullness, early satiation, and upper abdominal bloating, whereas placebo had no significant effect (all P < .05). Buspirone did not alter the rate of gastric emptying of solids or sensitivity to gastric distention, but it significantly increased gastric accommodation, compared with placebo (229 ± 28 vs 141 ± 32 mL, respectively; P < .05), and delayed gastric emptying of liquids (half-life = 64 ± 5 vs 119 ± 24 minutes, respectively). Adverse events were similar when patients were given buspirone or placebo.

Conclusions

In patients with FD, 4 weeks of administration of buspirone significantly improved symptoms and gastric accommodation, compared with placebo, whereas gastric emptying of liquids was delayed.

Section snippets

Patient Selection

Patients aged 20–70 years with FD according to Rome II criteria were eligible for the study.²⁰ Organic or metabolic disease was excluded by routine biochemistry, upper abdominal ultrasound, and upper gastrointestinal endoscopy. During endoscopy, biopsies were taken to assess the presence of Helicobacter pylori. Exclusion criteria were the presence of esophagitis, gastric atrophy, or erosive gastroduodenal lesions on endoscopy, heartburn as a predominant symptom, a history of peptic ulcer, major

Conduct of the Study

Twenty patients were recruited for the study. Three were excluded during the run-in phase, one because of pregnancy, one because the general practitioner started an antidepressant, and one who was hospitalized with vomiting.

Seventeen FD patients (13 women; mean age, 38.5 ± 2.4 years) were randomized to the study drug or placebo. Table 1 summarizes their symptom patterns at the end of the run-in period. Ten patients (58%) reported weight loss. All patients were H pylori negative; 4 patients had

Discussion

FD is a highly prevalent condition for which no treatment with well-established efficacy is presently available. Previous approaches to improve FD symptoms through acid-suppressive or prokinetic drugs have failed to generate substantial symptomatic benefit for the majority of patients.2, 3, 4 The use of prokinetics was based on the assumption that delayed gastric emptying was a major pathophysiological mechanism, but studies have identified impaired gastric accommodation and hypersensitivity to

References (34)

J. Tack et al.
Functional gastroduodenal disorders
Gastroenterology
(2006)
J. Tack et al.
Pathophysiology and treatment of functional dyspepsia
Gastroenterology
(2004)
J. Tack
Prokinetics and fundic relaxants in upper functional GI disorders
Curr Opin Pharmacol
(2008)
G. Sarnelli et al.
Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia
Am J Gastroenterol
(2003)
J. Tack et al.
Role of impaired gastric accommodation to a meal in functional dyspepsia
Gastroenterology
(1998)
J. Tack et al.
Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia
Gastroenterology
(2001)
J. Tack et al.
Role of tension receptors in dyspeptic patients with hypersensitivity to gastric distention
Gastroenterology
(2004)
J. Tack et al.
Clinical and pathophysiological characteristics of acute-onset functional dyspepsia
Gastroenterology
(2002)
Y.F. Ghoos et al.
Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test
Gastroenterology
(1993)
L. Van Oudenhove et al.
Central nervous system involvement in functional gastrointestinal disorders
Best Pract Res Clin Gastroenterol
(2004)

B. Geeraerts et al.

Influence of experimentally induced anxiety on gastric sensorimotor function in humans

Gastroenterology

(2005)

P. Blier et al.

Is there a role for 5-HT_1A agonists in the treatment of depression?

Biol Psychiatry

(2003)

P. Moayyedi et al.

Pharmacological interventions for non-ulcer dyspepsia

Cochrane Database Syst Rev

(2006)

S. Kindt et al.

Impaired gastric accommodation and its role in dyspepsia

Gut

(2006)

R. Bisschops et al.

Dysaccommodation of the stomach: therapeutic nirvana?

Neurogastroenterol Motil

(2007)

J. Tack et al.

Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans

Gut

(2002)

O.H. Gilja et al.

Effect of glyceryl trinitrate on gastric accommodation and symptoms in functional dyspepsia

Dig Dis Sci

(1997)

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Side effects and cognitive benefits of buspirone: A systematic review and meta-analysis
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Buspirone, a 5-hydroxytryptamine 1A (5-HT1A) receptor agonist, has been investigated for its use in various diseases. However, knowledge about its side effects and potential cognitive benefits in different conditions is limited. Cognitive impairment is also a prevalent symptom in many diseases, yet effective treatments are still lacking. Therefore, to explore the potential side effects of buspirone and the possible cognitive benefits of buspirone, we conducted a comprehensive search of several databases, including PubMed, Embase, Web of Science, Cochrane Review, Cochrane Trial, and ClinicalTrials.gov, to identify eligible randomized clinical trials. Our primary outcome measures included both side effects (adverse events) and cognitive benefits. For continuous variables, we utilized effect size with a 95% confidence interval (CI), whereas for dichotomous variables, we used odds ratios (OR) with a 95% CI. In total, 16 studies were included in this analysis, with 13 studies reporting on buspirone's side effects and 4 studies focusing on cognitive tasks. In terms of side effects, buspirone exhibited a higher rate of dizziness (OR = 4.66, 95% CI: 2.07–10.47), constipation (OR = 4.11, 95% CI: 1.34–12.55), and gastric distress (OR = 1.97, 95% CI: 1.03–3.78) than the placebo group. Regarding cognitive functions, buspirone showed significant benefits (g = 0.20, 95% CI: 0.06–0.34) while the placebo did not. Subgroup analysis indicated superior performance in visual learning and memory (g = 0.49, 95% CI: 0.21–0.78), logical reasoning (g = 0.42, 95% CI: 0.14–0.71), and attention (g = 0.37, 95% CI: 0.13–0.61) when compared to placebo. Our findings indicated that participants in the buspirone group experienced side effects of dizziness, constipation, and gastric distress in different diseases. Despite these adverse events, however, buspirone demonstrated significant cognitive benefits, particularly in the domains of visual learning and memory, logical reasoning, and attention.
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Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators, are often prescribed. Their therapeutic benefits alone or in combination remain unclear.
One hundred and twenty-nine patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time and gastric emptying scintigraphy. Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables.
In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (interquartile range, -1.25 to 0.05; P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy (P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores (P = .04) and all individual symptoms except nausea/vomiting (P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores (P ≤ .04) and most individual symptoms. Adjusting for gastric emptying time on multivariate analyses showed greater GCSI decreases for nondelayed emptying for neuromodulators as solo new therapy (P = .01). Gastric emptying scintigraphy, gender, diabetes, and functional dyspepsia did not influence responses to any treatment.
Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with nondelayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826.)
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Patients with a previous fundoplication operation and ongoing significant gastroduodenal symptoms and matched controls were included. BSGM using Gastric Alimetry (Alimetry Ltd) was employed, consisting of a high-resolution 64-channel array, validated symptom-logging application, and wearable reader.
A total of 16 patients with significant chronic symptoms after fundoplication were recruited, with 16 matched controls. Overall, 6 of 16 patients (37.5%) showed significant spectral abnormalities defined by unstable gastric myoelectrical activity (n = 2), abnormally high gastric frequencies (n = 3), or high gastric amplitudes (n = 1). Patients with spectral abnormalities had higher Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index scores than those of patients without spectral abnormalities (3.2 [range, 2.8–3.6] vs 2.3 [range, 2.2–2.8], respectively; P = .024). Moreover, 7 of 16 patients (43.8%) had BSGM test results suggestive of gut-brain axis contributions and without myoelectrical dysfunction. Increasing Principal Gastric Frequency Deviation and decreasing Rhythm Index scores were associated with symptom severity (r > .40; P < .05).
A significant number of patients with persistent postfundoplication symptoms displayed abnormal gastric function on BSGM testing, which correlated with symptom severity. Our findings advance the pathophysiologic understanding of postfundoplication disorders, which may inform diagnosis and patient selection for medical therapy and revisional procedures.
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Belching, bloating, and abdominal distention are all highly prevalent gastrointestinal symptoms and account for some of the most common reasons for patient visits to outpatient gastroenterology practices. These symptoms are often debilitating, affecting patients’ quality of life, and contributing to work absenteeism. Belching and bloating differ in their pathophysiology, diagnosis, and management, and there is limited evidence available for their various treatments. Therefore, the purpose of this American Gastroenterological Association (AGA) Clinical Practice Update is to provide best practice advice based on both controlled trials and observational data for clinicians covering clinical features, diagnostics, and management considerations that include dietary, gut-directed behavioral, and drug therapies.
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Clinical history and physical examination findings and impedance pH monitoring can help to differentiate between gastric and supragastric belching.
Treatment options for supragastric belching may include brain–gut behavioral therapies, either separately or in combination, such as cognitive behavioral therapy, diaphragmatic breathing, speech therapy, and central neuromodulators.
Rome IV criteria should be used to diagnose primary abdominal bloating and distention.
Carbohydrate enzyme deficiencies may be ruled out with dietary restriction and/or breath testing. In a small subset of at-risk patients, small bowel aspiration and glucose- or lactulose-based hydrogen breath testing may be used to evaluate for small intestinal bacterial overgrowth.
Serologic testing may rule out celiac disease in patients with bloating and, if serologies are positive, a small bowel biopsy should be done to confirm the diagnosis. A gastroenterology dietitian should be part of the multidisciplinary approach to care for patients with celiac disease and nonceliac gluten sensitivity.
Abdominal imaging and upper endoscopy should be ordered in patients with alarm features, recent worsening symptoms, or an abnormal physical examination only.
Gastric emptying studies should not be ordered routinely for bloating and distention, but may be considered if nausea and vomiting are present. Whole gut motility and radiopaque transit studies should not be ordered unless other additional and treatment-refractory lower gastrointestinal symptoms exist to warrant testing for neuromyopathic disorders.
In patients with abdominal bloating and distention thought to be related to constipation or difficult evacuation, anorectal physiology testing is suggested to rule out a pelvic floor disorder.
When dietary modifications are needed (eg, low–fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet), a gastroenterology dietitian should preferably monitor treatment.
Probiotics should not be used to treat abdominal bloating and distention.
Biofeedback therapy may be effective for bloating and distention when a pelvic floor disorder is identified.
Central neuromodulators (eg, antidepressants) are used to treat bloating and abdominal distention by reducing visceral hypersensitivity, raising sensation threshold, and improving psychological comorbidities.
Medications used to treat constipation should be considered for treating bloating if constipation symptoms are present.
Psychological therapies, such as hypnotherapy, cognitive behavioral therapy, and other brain–gut behavior therapies may be used to treat patients with bloating and distention.
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: Conflicts of interest The authors disclose no conflicts.

: Funding Supported by a Methusalem grant from Leuven University to Prof J. Tack.

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Original articleAlimentary tractEfficacy of Buspirone, a Fundus-Relaxing Drug, in Patients With Functional Dyspepsia

Background & Aims

Methods

Results

Conclusions

Section snippets

Patient Selection

Conduct of the Study

Discussion

Gastroenterology

Gastroenterology

Curr Opin Pharmacol

Am J Gastroenterol

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Best Pract Res Clin Gastroenterol

Gastroenterology

Biol Psychiatry

Pharmacological interventions for non-ulcer dyspepsia

Cochrane Database Syst Rev

Impaired gastric accommodation and its role in dyspepsia

Gut

Dysaccommodation of the stomach: therapeutic nirvana?

Neurogastroenterol Motil

Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans

Gut

Effect of glyceryl trinitrate on gastric accommodation and symptoms in functional dyspepsia

Dig Dis Sci

Original article
Alimentary tract
Efficacy of Buspirone, a Fundus-Relaxing Drug, in Patients With Functional Dyspepsia