CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2012;10:1239 1245

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

Functional Dyspepsia
JAN TACK, PIETER JANSSEN, TATSUHIRO MASAOKA, RICARD FARR, and LUKAS VAN OUDENHOVE
Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium

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.
Keywords: Gastric Barostat; Therapy; Clinical Trial; Mechanoreceptor.

unctional dyspepsia (FD), defined as the presence of symptoms thought to originate in the gastroduodenal region in
the absence of organic, systemic, or metabolic disease that is
likely to explain the symptoms, is one of the most common
gastrointestinal disorders.1 According to the Rome III consensus, typical FD symptoms are early satiation, postprandial fullness, epigastric pain, and epigastric burning. Other symptoms
such as upper abdominal bloating, belching, and nausea often
coexist, and a subset of patients may experience weight loss.1,2
At present, there is no treatment with established efficacy for
FD. Proton pump inhibitors and prokinetic drugs are most
frequently used, although the evidence to support their efficacy
is limited.3 The rationales for the use of these classes of drugs
are the frequent overlap with gastroesophageal reflux disease

and the hypothesis that delayed gastric emptying is an important underlying pathophysiological mechanism, respectively.4
However, it has become clear that delayed gastric emptying is
only present in a minority of FD patients.5
Several studies have reported impaired gastric accommodation in FD, which may contribute to symptom generation.6 8
Gastric accommodation is a relaxation of the proximal stomach
that occurs during meal ingestion and provides the meal with a
reservoir, enabling a gastric volume increase without a rise in
pressure.7,8 Impaired accommodation is present in approximately 40% of FD patients and is associated with more prevalent symptoms of early satiation and weight loss.6 On the basis
of observations in healthy controls and in FD patients, restoration of accommodation is considered a valid therapeutic
target.6 8 Besides delayed gastric emptying and impaired accommodation, hypersensitivity to gastric distention is another
prevalent pathophysiological abnormality in FD.9 Mechanistic
studies have established that tension-sensitive mechanoreceptors are involved in symptom generation in FD patients with
hypersensitivity to gastric distention and that drugs that relax
the proximal stomach have a potential to improve symptoms in
these patients.10
Targeting impaired accommodation or visceral hypersensitivity in FD through enhanced relaxation of the proximal stomach is hampered by a lack of suitable pharmacologic tools for
human use. Because nitric oxide is the major neurotransmitter
mediating gastric relaxation, nitric oxide donors have been used
to enhance gastric relaxation and to reduce dyspeptic symptoms, but their effect was short-lasting and accompanied by
vascular side effects.11,12 Animal studies identified a 5-hydroxytryptamine (5-HT)1p receptor on nitrergic enteric neurons as a
suitable target, and studies in humans confirmed the ability of
the 5-HT1 receptor agonist sumatriptan to relax the proximal
stomach through a nitrergic pathway.6,1316 However, because of
its low bioavailability when taken orally and because of its
pharmacologic profile, sumatriptan is less suitable for FD therapy.17 Activation of presynaptic 5-HT1A receptors on cholinergic
nerve endings is another pathway that relaxes the proximal
stomach in animal models.18 In healthy volunteers, buspirone,
a 5-HT1A receptor agonist used in the treatment of anxiety,
dose-dependently relaxed the proximal stomach and delayed
gastric emptying of solids and liquids.19
Abbreviations used in this paper: DSS, dyspepsia symptom severity;
FD, functional dyspepsia; 5-HT, 5-hydroxytryptamine; SCL-90R, Symptom Checklist-90-Revised.
2012 by the AGA Institute
1542-3565/$36.00
http://dx.doi.org/10.1016/j.cgh.2012.06.036

1240

TACK ET AL

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 10, No. 11

Our aim was to study the influence of buspirone on symptoms, gastric emptying rate, gastric accommodation, and sensitivity to gastric distention in FD patients.

Methods
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 abdominal surgery, and the use of nonsteroidal
anti-inflammatory drugs, steroids, prokinetics, or drugs affecting gastric acid secretion.
All patients were seen by a psychiatrist for a structured
psychiatric interview.21 Patients with current anxiety or depression and patients treated with antipsychotics or antidepressants
during the last 6 weeks were not eligible for the study. The
psychiatrist also ruled out anorexia nervosa in patients with
weight loss. Pregnant female patients or patients of childbearing potential without effective contraception were also excluded. All drugs potentially affecting gastrointestinal motility
or sensitivity were discontinued at least 1 week before the start
of the study and were forbidden for the entire course of the
study. Informed consent was obtained from each participant.
The protocol was approved by the Ethics Committee of the
University Hospital.

Study Design
After a 2-week run-in period, the study consisted of two
4-week treatment periods, separated by a 2-week washout (Figure 1). Treatment consisted of buspirone 10 mg or matching
placebo 3 times daily 15 minutes before meals. Patients filled
out a dyspepsia symptom severity (DSS) score at the end of the
run-in period, at the end of the washout period, and at the end
of each treatment period. In this questionnaire, whose reproducibility and sensitivity have previously been reported, patients scored the intensity of 8 dyspeptic symptoms (epigastric
pain, postprandial fullness, upper abdominal bloating, early
satiation, nausea, vomiting, epigastric burning, belching) during the last week on a Likert scale (range, 0 3 [absent, mild,
moderate, severe]).22,23 DSS is defined as the sum of all 8 items.
At the beginning of the study, an extensive clinical psychiatric
assessment was performed, and patients filled out the Symptom
Checklist-90-Revised (SCL-90R) questionnaire.
At the end of the run-in period and at the end of each
treatment period, all patients underwent a gastric barostat
study and a gastric emptying study with registration of mealrelated symptoms. The details of these measurements are outlined below.

Gastric Emptying Breath Test and

Meal-Related Symptoms
Gastric solid and liquid emptying rates were determined by the 14C-octanoic acid and 13C-glycin breath test,
respectively.24,25 In the treatment phases, study medication was
ingested 15 minutes before the meal. Breath samples were taken

Figure 1. (A) Number of patients included and selected for randomization. (B) Outline of the study protocol. AE, adverse event.

before the meal and at 15-minute intervals during 240 minutes

postprandially and were analyzed as previously reported.24,25
At each breath sampling, the patient was asked to grade the
intensity (0 3) of 6 epigastric symptoms (epigastric pain, bloating, postprandial fullness, nausea, belching, and epigastric
burning).26

Gastric Barostat Studies

Gastric barostat studies to assess sensitivity to gastric
distention and meal-induced accommodation were performed
as previously reported.6,8

Data Analysis
Gastric half-emptying time was calculated from the
and 14CO2 excretion curves as previously reported and
validated.24,25 For each symptom, a meal-related severity score
was obtained by adding scores at all time points. A cumulative
meal-related symptom score was obtained by adding individual
symptom severity scores.26
Gastric barostat studies were analyzed as previously reported.6,9 Hypersensitivity to gastric distention was defined as a
discomfort threshold 6.6 mm Hg above intragastric pressure.
Impaired accommodation to a meal was defined as a mealinduced relaxation 64 mL.6,9
13CO
2

Statistical Analysis
Data are presented as mean standard error of the
mean. The primary outcome variable was the improvement in
DSS scores. DSS scores after 4 weeks of treatment were compared with the scores at the end of the preceding period off
therapy (run-in period or washout period, depending on treatment order allocation). To evaluate carryover effects, DSS
scores at the end of run-in and the end of washout were also

November 2012

BUSPIRONE IN FUNCTIONAL DYSPEPSIA

1241

compared. The study was powered to detect a 30% difference in

symptom scores with 85% sensitivity at P .05.
Secondary outcome variables were the effects of treatment
on meal-related symptom severity score, on solid and liquid
gastric emptying rates, on gastric compliance, thresholds during gastric balloon distention, and meal-induced gastric accommodation. Because gastric barostat and meal-related symptom
assessment with gastric emptying were only performed at baseline and at the end of each treatment period, these analyses
compared baseline with on-therapy measures.
The correlation between changes in DSS scores and the
baseline SCL-90R scores, changes in gastric emptying rate, and
changes in barostat parameters were assessed by Pearson correlation analysis. A similar correlation analysis was done for
changes in meal-related symptom scores.
Symptom scores and changes in measured variables of gastric sensorimotor function were compared by paired t test.
Differences were considered significant, with P .05.

Results
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 a history of H pylori
infection, with eradication 6 months before the study. At
baseline, anxiety and depression levels, as assessed by the SCL90R questionnaire, were 15.2 1.2 and 33.3 3.0, respectively,
which is below the Dutch norms for psychiatric outpatients (25
and 43, respectively). Seven patients were randomized to receive
buspirone first, and 10 patients received placebo first. Both
groups did not differ in mean age (35 5 vs 41 2.0 years;
P .18) and in sex distribution (2/7 vs 2/10 males; NS).
Two patients (one female) stopped the study during the first
week of treatment (one on buspirone, one on placebo) because
of nausea and abdominal discomfort. In one patient with poor
tolerance of the barostat, no repeat barostats were performed.
All other patients finished the protocol as planned.

Table 1. Symptom Profile in Patient Population at End of

Run-in Period (N 17)
Symptom

Absent

Mild

Moderate

Severe

Postprandial fullness
Upper abdominal bloating
Early satiation
Nausea
Belching
Epigastric pain
Vomiting
Epigastric burning

1
3
6
4
4
8
12
8

2
1
2
2
4
3
0
4

4
5
3
6
5
2
2
5

10
8
6
5
4
4
3
0

NOTE. Rows indicate number of patients for each symptom severity level.

Figure 2. (A) Influence of buspirone and placebo on DSS. (B) Influence

of buspirone and placebo on severity scores of individual dyspeptic
symptoms. *P .05 compared with baseline.

Dyspepsia Symptom Severity

DSS before placebo treatment was 10.8 1.0, and no
significant difference occurred after placebo (9.5 1.1; NS).
Before buspirone treatment, DSS was 11.5 1.2, and this was
significantly decreased after 4 weeks of buspirone therapy to
7.5 1.3 (P .005). The difference in DSS at the end of
placebo and buspirone treatment was borderline significant
(P .05) (Figure 2A).
Compared with the end of the pretreatment phase, the
individual symptoms of postprandial fullness (2.2 0.2 vs
1.3 0.3; P .005), upper abdominal bloating (2.2 0.2 vs
1.6 0.3; P .005), and early satiation (1.6 0.3 vs 0.5 0.3;
P .005) were significantly improved by buspirone but not by
placebo treatment (Figure 2B). The severity of postprandial
fullness was significantly lower after 4 weeks of buspirone
compared with placebo (1.3 0.3 vs 1.9 0.2; P .05).

Meal-Related Symptom Scores and Gastric

Emptying Rates
Table 2 and Figure 3 summarize the meal-related symptom scores and gastric emptying rates. No significant changes
in solid emptying occurred, whereas liquid gastric emptying was
significantly slower after buspirone compared with baseline
(Table 2). Delayed gastric emptying was found in 2 patients at

1242

TACK ET AL

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 10, No. 11

Table 2. Influence of Placebo and Buspirone on Different Parameters of Gastric Sensorimotor Function Testing
Test

Variable

Baseline

Placebo

Buspirone

Gastric emptying rate

Solid emptying half-emptying time (min)

Liquid emptying half-emptying time (min)
MDP (mm Hg)
Fasting discomfort threshold (mm Hg above MDP)
Fasting discomfort volume (mL)
Gastric accommodation (mL)
Postprandial discomfort threshold (mm Hg above MDP)
Postprandial discomfort volume (mL)

95 16
64 5
6.6 0.6
5.5 0.3
406 21
132 40
8.6 2.1
523 84

88 6
80 6
7.1 0.6
5.3 0.5
367 47
141 32
7.7 1.3
457 54

110 17
119 24a
5.9 0.7
5.9 0.4
380 25
229 28a,b
6.4 0.9
593 49b

Gastric barostat

MDP, minimal distending pressure.

aP .05 compared with baseline.
bP .05 compared with placebo.

baseline, 3 during placebo treatment, and 5 during buspirone

treatment (NS). Rapid gastric emptying, defined as half-emptying time below the 95% confidence interval in healthy volunteers (44 minutes for solids, 35 minutes for liquids), was
found in only one patient at baseline (44 minutes for solids, 37
minutes for liquids).
Total meal-related symptom severity scores were significantly
lower after buspirone compared with baseline (67 17 vs 119
24; P .005) or with placebo (67 17 vs 97 15; P .01),
whereas baseline and placebo did not differ significantly (Figure
3A).

Compared with baseline, buspirone significantly improved

meal-related symptom severities for postprandial fullness (27
6 vs 14 5; P .005), upper abdominal bloating (26 6 vs
14 4; P .05), nausea (20 5 vs 12 4; P .01), and
belching (24 4 vs 12 3; P .005), whereas placebo only
improved belching (24 4 vs 16 3; P .05). Compared with
placebo, buspirone was associated with significantly lower mealrelated symptom severity of postprandial fullness (23 5 vs
14 5; P .05) and upper abdominal bloating (22 5 vs 14
4; P .05) (Figure 3B).

Gastric Barostat Studies

Table 2 summarizes the results of the gastric barostat
studies. No significant differences were found between baseline,
placebo, and buspirone for minimal distending pressure, sensitivity to gastric distention in the fasting and postprandial state
(Figure 4A), and gastric compliance. Hypersensitivity to fasting
gastric distention was found in 13 patients at baseline, in 12
during placebo, and in 10 during buspirone (NS).
Preprandial intraballoon volumes did not differ between the
3 conditions. Postprandial intraballoon volumes tended to be
higher after buspirone compared with placebo (367 35 vs
276 28; P .05). Gastric accommodation was significantly
higher after buspirone compared with placebo (229 28 vs
141 32; P .05) (Figure 4B). Impaired accommodation to
meal was found in 5 patients at baseline, in 6 during placebo
treatment (NS), and in 1 during buspirone treatment (P .09).

Correlates of Symptom Evolution

The improvements in DSS and in meal-related symptoms were not significantly correlated to demographics, baseline severity scores, baseline anxiety and depression scores, and
baseline gastric emptying or barostat characteristics. Significant
correlations were found between the improvement in DSS and
changes in solid and liquid gastric half-emptying times (R2
0.30 and R2 0.27, respectively; both P .04). Borderline
significant correlations were found between changes in gastric
accommodation and improvement in postprandial fullness and
in upper abdominal bloating (R2, 0.26 and 0.24, respectively;
P .05 and .06, respectively).
Figure 3. (A) Influence of buspirone and placebo on gastric emptying
and total meal-related symptom severity. (B) Influence of buspirone and
placebo on individual meal-related symptom severity. *P .05 vs
run-in; **P .005 vs baseline; P .05 vs placebo.

Carryover Effect
In crossover studies, symptom severity may fail to return to baseline after the first treatment period. In the present
study, DSS scores at the end of 2-week washout after the initial

November 2012

Figure 4. (A) Influence of buspirone and placebo on gastric sensitivity

to fasting and postprandial balloon distention. (B) Influence of buspirone
and placebo on intraballoon volumes before and after a meal.

treatment period did not differ significantly from baseline

(11.4 1.2 vs 10.9 0.9; NS).
To further address the issue of a carryover effect, a separate
analysis of the first treatment period as a parallel group study
was performed, although numbers for this analysis are very low.
According to this analysis, buspirone significantly decreased
DSS (5.7 1.8 vs 9.7 0.9; P .01) compared with baseline,
and the individual symptoms of postprandial fullness (1.0
1.4 vs 2.2 0.3; P .05) and belching (0.8 0.3 vs 1.8 0.3;
P 0.05). In contrast, placebo had no significant effect on
overall (9.8 1.7 vs 11.5 1.4; NS) and individual symptom
scores compared with baseline. No significant differences in
symptom intensities were found at the end of the first treatment phase between placebo and buspirone in this parallel
group analysis.

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 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 gastric distention as potentially more relevant factors underlying FD symptom generation.2,59 In acute
studies, relaxation of the proximal stomach has been identified

BUSPIRONE IN FUNCTIONAL DYSPEPSIA

1243

as a target to improve symptoms in FD patients with impaired

accommodation and hypersensitivity to gastric distention, and
5-HT1A agonists have been identified as a class of agents that
induce gastric relaxation.6 10,19,27
In the present proof-of-concept study evaluating symptoms
and mechanisms, we demonstrated that the 5-HT1A agonist
buspirone was superior to placebo in alleviating FD symptoms,
more specifically early satiation, postprandial fullness, and upper abdominal bloating. Improvement was apparent both from
an FD symptom severity questionnaire28 and from the assessment of postprandial symptoms after a standardized meal.26
Buspirone seemed most effective for the meal-related FD symptoms of early satiation, upper abdominal bloating, and postprandial fullness, whereas symptoms of epigastric pain and
burning were not affected, suggesting that this treatment approach may be most beneficial for the FD subgroup with
postprandial distress syndrome according to Rome III criteria.1
The observations are in agreement with a recent large placebocontrolled study from Japan, which showed significant benefit
from a 4-week treatment with the 5-HT1A agonist tandospirone
compared with placebo.29 Taken together, these studies support
a therapeutic benefit of 5-HT1A receptor agonists in FD. On the
other hand, a smaller mechanistic study with R137696, another
5-HT1A agonist, failed to demonstrate symptomatic benefit, but
there was a suggestion of lack of drug effect on repeated
administration.30
The 5-HT1A agonists may improve FD symptom severity
through a number of mechanisms. Both buspirone and tandospirone are clinically used as anxiolytic drugs. The comorbidity between functional gastrointestinal disorder and psychiatric disorders, especially anxiety disorders, is high,31 and
experimentally induced anxiety in healthy volunteers is associated with decreased gastric compliance and accommodation
and increased epigastric symptom scores during a standard
nutrient challenge.32 In hypersensitive FD patients, state anxiety
is significantly correlated with lower discomfort and pain
thresholds and decreased compliance during gastric balloon
distention.33 These observations suggest a potential for anxiolytics to alter both FD symptoms and gastric sensorimotor
function. In the present article, baseline anxiety scores were not
correlated to symptom improvement, but because these scores
were not repeated at the end of treatment, we are unable to
correlate changes in anxiety levels with improvement in FD
symptoms. This, together with the relatively low number of
patients studied, is the main limitation of the present proofof-concept study. On the other hand, in the much larger tandospirone controlled trial, no correlation was found between
anxiety scores and symptom improvement, arguing against an
anxiolytic effect as a main mechanism underlying symptom
improvement with 5-HT1A agonists in FD.29
Symptom improvement in the present study was associated
with a delay in liquid gastric emptying rate and an increase in
meal-induced gastric accommodation. These data suggest that
the inhibitory effect of buspirone on proximal stomach tone is
an important contributor to its therapeutic efficacy. The small
sample size of the current study does not allow comparisons of
symptomatic benefit in specific subgroups such as patients with
impaired accommodation or visceral hypersensitivity. A significant correlation was found between slowing of gastric emptying and symptom improvement by buspirone. However, with
only one patient with rapid gastric emptying at baseline, delay-

1244

TACK ET AL

ing gastric emptying rate per se is unlikely to mediate the effects

of buspirone. The increase in gastric accommodation was borderline significantly correlated to the improvement of symptoms by buspirone treatment. Taking into account the prevalence of impaired accommodation at baseline and during
buspirone of 6 and 1 patients, respectively, it is conceivable that
enhancement of gastric accommodation underlies some of the
observed symptomatic benefit. Confirmation in a larger study
would strengthen this hypothesis, but measuring accommodation with a barostat or with other techniques is technically
difficult, which tends to preclude large-scale studies.7,8
The dose of buspirone, 10 mg 3 times daily, was based on
previous pharmacodynamic studies in healthy volunteers that
showed that acute administration of this dose did cause a delay
in solid gastric emptying; the latter is potentially undesirable
for FD symptom treatment.19 Buspirone was well tolerated in
the present study, with an adverse event and treatment interruption incidence similar to placebo. When used in large patient samples for anxiolytic purposes, buspirone use has been
associated with dizziness, lightheadedness, and nausea.34 Larger-scale therapeutic studies with buspirone to further assess its
efficacy and tolerability profile in FD seem warranted on the
basis of our study.
In conclusion, in a placebo-controlled crossover trial, 4
weeks of treatment with the 5-HT1A receptor agonist buspirone
10 mg 3 times daily significantly improved overall symptom
severity and the individual symptoms of early satiation, postprandial fullness, and upper abdominal bloating. The therapeutic effect was associated with a slowed liquid gastric emptying
and enhanced gastric accommodation. Buspirone 10 mg 3
times daily was well tolerated in this proof-of-concept study,
and larger studies in FD seem warranted.

References
1. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal
disorders. Gastroenterology 2006;130:1466 1479.
2. Tack J, Bisschops R, Sarnelli G. Pathophysiology and treatment
of functional dyspepsia. Gastroenterology 2004;127:1239
1255.
3. Moayyedi P, Soo S, Deeks J, et al. Pharmacological interventions
for non-ulcer dyspepsia. Cochrane Database Syst Rev 2006;4:
122.
4. Tack J. Prokinetics and fundic relaxants in upper functional GI
disorders. Curr Opin Pharmacol 2008;8:690 696.
5. Sarnelli G, Caenepeel P, Geypens B, et al. Symptoms associated
with impaired gastric emptying of solids and liquids in functional
dyspepsia. Am J Gastroenterol 2003;98:783788.
6. Tack J, Piessevaux H, Coulie B, et al. Role of impaired gastric
accommodation to a meal in functional dyspepsia. Gastroenterology 1998;115:1346 1352.
7. Kindt S, Tack J. Impaired gastric accommodation and its role in
dyspepsia. Gut 2006;55:16851691.
8. Bisschops R, Tack J. Dysaccommodation of the stomach: therapeutic nirvana? Neurogastroenterol Motil 2007;19:8593.
9. Tack J, Caenepeel P, Fischler B, et al. Symptoms associated with
hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology 2001;121:526 535.
10. Tack J, Caenepeel P, Corsetti M, et al. Role of tension receptors
in dyspeptic patients with hypersensitivity to gastric distention.
Gastroenterology 2004;127:1058 1066.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 10, No. 11

11. Tack J, Demedts I, Meulemans A, et al. Role of nitric oxide in the

gastric accommodation reflex and in meal induced satiety in
humans. Gut 2002;51:219 224.
12. Gilja OH, Hausken T, Bang CJ, et al. Effect of glyceryl trinitrate on
gastric accommodation and symptoms in functional dyspepsia.
Dig Dis Sci 1997;42:2124 2131.
13. Tack J, Vanden Berghe P, Coulie B, et al. Sumatriptan is an
agonist at 5-HT receptors on myenteric neurones in the guinea-pig gastric antrum. Neurogastroenterol Motil 2007;19:
39 46.
14. Coulie B, Tack J, Sifrim D, et al. Role of nitric oxide in fasting
gastric fundus tone and in 5-HT1 receptor-mediated relaxation of
gastric fundus. Am J Physiol 1999;276:G373G377.
15. Tack J, Coulie B, Wilmer A, et al. Influence of sumatriptan on
gastric fundus tone and on the perception of gastric distension in
man. Gut 2000;46:468 473.
16. Tack J, Demedts I, Dehondt G, et al. Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology 2002;122:1738 1747.
17. Sarnelli G, Janssens J, Tack J. Effect of intranasal sumatriptan on
gastric tone and sensitivity to distension. Dig Dis Sci 2001;46:
15911595.
18. Tack JF, Janssens J, Vantrappen G, et al. Actions of 5-hydroxytryptamine on myenteric neurons in guinea pig gastric antrum.
Am J Physiol 1992;263:G838 G846.
19. Van Oudenhove L, Kindt S, Vos R, et al. Influence of buspirone on
gastric sensorimotor function in man. Aliment Pharmacol Ther
2008;28:1326 1333.
20. Talley NJ, Stanghellini V, Heading RC, et al. Functional gastroduodenal disorders. Gut 1999;45(Suppl 2):II37II42.
21. First MB, Spitzer RL, Gibbon M, et al. Structured clinical interview
for DSM-IV axis I disorders. New York: Biometrics Research
Department, New York State Psychiatric Institute, 1996.
22. Cuomo R, Sarnelli G, Grasso R, et al. Functional dyspepsia
symptoms, gastric emptying and satiety provocative test: analysis of relationships. Scand J Gastroenterol 2001;36:1030
1036.
23. Kindt S, Van Oudenhove L, Mispelon L, et al. Longitudinal and
cross-sectional factors associated with long-term clinical course
in functional dyspepsia: a 5-year follow-up study. Am J Gastroenterol 2011;106:340 348.
24. Ghoos YF, Maes BD, Geypens BJ, et al. Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test. Gastroenterology 1993;104:1640
1647.
25. Maes BD, Ghoos YF, Geypens BJ, et al. Combined carbon-13glycine/carbon-14-octanoic acid breath test to monitor gastric
emptying rates of liquids and solids. J Nucl Med 1994;35:824
831.
26. Arts J, Caenepeel P, Verbeke K, et al. Influence of erythromycin
on gastric emptying and meal related symptoms in functional
dyspepsia with delayed gastric emptying. Gut 2005;54:455
460.
27. Boeckxstaens GE, Tytgat GN, Wajs E, et al. The influence of the
novel 5-HT1A agonist R137696 on the proximal stomach function in healthy volunteers. Neurogastroenterol Motil 2006;18:
919 926.
28. Van Oudenhove L, Vandenberghe J, Geeraerts B, et al. Determinants of symptoms in functional dyspepsia: gastric sensorimotor
function, psychosocial factors or somatisation? Gut 2008;57:
1666 1673.
29. Miwa H, Nagahara A, Tominaga K, et al. Efficacy of the 5-HT1A
agonist tandospirone citrate in improving symptoms of patients
with functional dyspepsia: a randomized controlled trial. Am J
Gastroenterol 2009;104:2779 2787.

November 2012

30. Tack J, van den Elzen B, Tytgat G, et al. A placebo-controlled trial

of the 5-HT agonist R-137696 on symptoms, visceral hypersensitivity and on impaired accommodation in functional dyspepsia.
Neurogastroenterol Motil 2009;21:619 626.
31. Van Oudenhove L, Demyttenaere K, Tack J, et al. Central nervous
system involvement in functional gastrointestinal disorders. Best
Pract Res Clin Gastroenterol 2004;18:663 680.
32. Geeraerts B, Vandenberghe J, Van Oudenhove L, et al. Influence of experimentally induced anxiety on gastric sensorimotor function in humans. Gastroenterology 2005;129:1437
1444.
33. Van Oudenhove L, Vandenberghe J, Geeraerts B, et al. Relationship between anxiety and gastric sensorimotor function
in functional dyspepsia. Psychosom Med 2007;69:455
463.

BUSPIRONE IN FUNCTIONAL DYSPEPSIA

1245

34. Blier P, Ward NM. Is there a role for 5-HT1A agonists in the
treatment of depression? Biol Psychiatry 2003;53:193203.

Reprint requests
Address requests for reprints to: Jan Tack, MD, PhD, Department of
Pathophysiology, Division of Gastroenterology, University Hospitals
Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. e-mail: jan.
tack@med.kuleuven.ac.be; fax: 32-16-34-44-19.
Conicts of interest
The authors disclose no conicts.
Funding
Supported by a Methusalem grant from Leuven University to Prof J.
Tack.