A PROSPECTIVE STUDY: DOES CITALOPRAM INCREASE THE

Acta Medica Mediterranea, 2013, 29: 125
A PROSPECTIVE STUDY: DOES CITALOPRAM INCREASE THE REFLUX SYMPTOMS?
TIMUCIN AYDOGAN*, MEHMET ALI EREN**, TURGAY ULAS**, FATIH KARABABA***, SALIH SELEK****, IBRAHIM ARSLAN**,
AHMET UYANIKOGLU*, IDRIS KIRHAN**, HASIM NAR*
*Harran University, Faculty of Medicine, Department of Gastroenterology, Sanliurfa - **Harran University, Faculty of Medicine,
Department of Internal Medicine, Sanliurfa - ***Harran University, Faculty of Medicine, Department of Psychiatry, Sanliurfa ****Medeniyet University, Faculty of Medicine, Department of Psychiatry, Istanbul
[Uno studio prospettico: Citalopram aumentare i sintomi di reflusso?]
ABSTRACT
Objective: Selective serotonin reuptake inhibitors (SSRIs) induce some adverse effects on gastrointestinal system. We aimed to
investigate the role of citalopram, a well-known SSRI, on the reflux symptoms.
Methods: Seventy patients with gastro-oesophageal reflux disease (GERD) were included to the study. Anxiety and depressive
symptoms were measured with the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI), version II, respectively.
Participants were divided into two groups: Group 1 (n=35) treated with only esomeprazole + sodium alginate and Group 2 (n=35)
who were classified as moderate-severe depression and/or anxiety treated with esomeprazole + sodium alginate + citalopram.
Results: At the beginning, BDS and BAS were significantly higher in Group 2 than in Group 1 (both p<0.001) and BAS and
BDS were significantly decreased with the treatments in both groups (both p<0.001). Moreover, the numbers of the patient who said
the reflux symptoms improved were significantly higher in Group 1 than in Group 2 (p=0.001).
Conclusions: The administration of citalopram to patients with GERD caused the distribution of recovery of the reflux symptoms. This relation should be taken into account when managing depression in the patients with severe reflux symptoms.
Key words: Gastro-oesophageal reflux disease, citalopram, anxiety, depression
Received January 16, 2013; Accepted January 21, 2013
Introduction
Gastro-oesophageal reflux disease (GERD) is
a chronic and a common health problem; it affects
approximately 10–20% of adults(1). Depression is
also a most common health problem(2). At the same
time, an association between GERD and depression
has been shown in several studies (3-5). Selective
serotonin reuptake inhibitors (SSRIs) induce some
gastrointestinal adverse effects such as anorexia,
nausea, dyspepsia, diarrhea and upper gastrointestinal bleeding(6). Otherwise, SSRIs may be a beneficial option for treatment of hypersensitive esophagus(7). However, the effects of SSRIs on the reflux
symptoms remain controversial.
Although based upon the side effects of SSRIs
on gastrointestinal system mentioned above, no
research study has been performed yet to show the
effect of SSRIs on reflux symptoms. By this way,
we aimed to investigate the role of citalopram, a
well-known antidepressant drug and a SSRI,
whether the treatment increases or not the reflux
symptoms.
Material and method
Study population
The study was conducted in a prospective way
in our gastroenterology outpatient unit and 70
patients diagnosed GERD were included. At the
beginning, the study protocol was reviewed and
approved by the local ethics committee, in accordance with the ethical principles for human investi-
126
Timucin Aydogan, Mehmet Ali Eren et Al
gations, as outlined by the Second Declaration of
Helsinki, and written informed consent was
obtained from all the patients.
Exclusion criteria included a past history of
gastrointestinal surgery, gastric and duodenal ulcer,
the concurrent presence of organic diseases including cancer and unwillingness of questionnaire.
GERD diagnosis was made by occurring of
typical symptoms (heatburn and/or regurtitation) at
a frequency higher than twice a week and for a
period longer than 4 weeks(8,9). All participants in
the current study were administered esomeprazole
40 milligram twice a day and sodium alginate 4 x
500 milligram for three months. Anxiety symptoms
were measured using the Beck Anxiety Inventory
(BAI) and depressive symptoms were measured
with the Beck Depression Inventory (BDI), version
II (10-12). Patients who had BAI score (BAS) > 15
and/or BDI score (BDS) > 16 were treated additionally with citalopram 10 milligram/day for three
months, which were classified as moderate-severe
depression and/or anxiety. Participants were divided
into two groups: Group 1 (n=35) treated with only
esomeprazole + sodium alginate and Group 2
(n=35) treated with esomeprazole + sodium alginate + citalopram. At the end of the study patients
were asked for the recovery of present reflux symptoms and categorized as i) Completely resolved, ii)
Significantly reduced, iii) Slightly reduced and iv)
Unchanged.
Statistical analysis
All statistical analyses were performed using
SPSS 15.0 for Windows (SPSS, Chicago, IL, USA).
Continuous variables were expressed as mean ±
standard deviation (SD) and categorical variables
were expressed as percentages. Either χ2 test or
Student’s unpaired t-test were used to compare the
categorical or continuous variables, respectively.
Paired t-test was used to analyze changes within the
groups. A two-sided p value < 0.05 was considered
to be statistically significant.
Results
There were no significant differences in baseline demographic features and clinical findings
other than BDS and BAS between two groups
(Table 2). BDS and BAS were significantly higher
in Group 2 than in Group 1 at the beginning (both
p<0.001). BAS and BDS were significantly
decreased with the treatments in both groups (both
p<0.001). Moreover, the numbers of the patient
who said the reflux symptoms improved were significantly higher in Group 1 than in Group 2 especially in the terms of patients who said “Completely
resolved” (p=0.001).
Discussion
The data of this study reveal that i) depression
and anxiety scores were decreased in both treatment
group suggest us that the association between anxiety, depression and reflux; ii) reflux symptoms were
not resolved in the citalopram group suggest us that
citalopram has worsening effect on reflux.
The previous study by Jansson et al. demonstrated the correlation between the anxiety, depression and reflux symptoms and they found that 2.8
times increased reflux symptoms in present of anxiety and depression(3). Marti´N-Merino et al. found
an increased incidence of GERD among patients
with depression(13). At the same time anxiety, but not
depression, has found to be independent factor for
the determining of health care utilization in dyspeptic patients(4). Patients with GERD have impaired
quality of life compared with general populations
and psychological factors could affect the clinical
manifestations of reflux disease(14,15). We showed
that treatment of reflux disease provided improvement in depression and anxiety scores independent
from anti-depressant treatment.
SSRIs had a direct damaging effect on the gastrointestinal mucosa and related with the increased
prevalence of gastric mucosal damage (16,17) .
However, it has been showed that citalopram can
mitigate inflammation-induced exacerbation of gastric ulcers and augment the gastric mucus barrier(18).
SSRIs augment the availability of physiologically
released 5-hydroxytryptamine (5-HT) which is a
neurotransmitter in the enteric nervous system and
play a key role in the control of gastrointestinal
motility(19,20). Acute effects of citalopram as a selective 5-HT reuptake inhibitor include decreasing of
basal gastric tone, impairing gastric accommodation to a meal, enhancing gastric emptying of solids
and increasing the volume of nutrient drink ingested before maximal satiation(20). Citalopram significantly decreases the of mechanical and chemical
sensitivity the esophagus and SSRIs treatment may
be a reasonable and beneficial option for the hypersensitive esophagus(7,21).
Besides all of this knowledge, the effect of
A prospective study: Does Citalopram Increase the Reflux Symptoms?
citalopram on the symptoms of GERD is not
known. We found that reflux symptoms were not
resolved in citalopram treated group as well as
other treatment group that not include citalopram.
The side effects of citalopram related with gastrointestinal system especially on reflux disease seem to
occur over the inhibition of 5-HT reuptake. As discussed above, citalopram may be a treatment option
for hypersensitive esophagus. However, present
study unable to exclude patient with hypersensitive
esophagus because of lack of upper gastrointestinal
system endoscopy and 24 hour pHmeter. It is the
most important limitation of our study.
127
9)
10)
11)
12)
13)
Conclusion
In the present study, the administration of
citalopram to patients with GERD caused the distribution of recovery of the reflux symptoms. This
study provides further evidence for the relationship
between citalopram and GERD. This relation
should be taken into account when managing
depression in the patients with severe reflux symptoms.
14)
15)
16)
17)
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_________
Request reprints from:
Assist. Prof. Dr. Timucin Aydogan
Harran University School of Medicine
Department of Internal Medicine and Gastroenterology
Yenisehir Campus, 63000, Sanliurfa
(Turkey)