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 saidthe 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 symp- toms. 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
research study has been performed yet to show theeffect of SSRIs on reflux symptoms. By this way,
Gastro-oesophageal reflux disease (GERD) is
we aimed to investigate the role of citalopram, a
a chronic and a common health problem; it affects
well-known antidepressant drug and a SSRI,
approximately 10–20% of adults(1). Depression is
whether the treatment increases or not the reflux
also a most common health problem(2). At the same
time, an association between GERD and depressionhas been shown in several studies(3-5). Selective
Material and method
serotonin reuptake inhibitors (SSRIs) induce somegastrointestinal adverse effects such as anorexia,
Study population
nausea, dyspepsia, diarrhea and upper gastrointesti-nal bleeding(6). Otherwise, SSRIs may be a benefi-
The study was conducted in a prospective way
cial option for treatment of hypersensitive esopha-
in our gastroenterology outpatient unit and 70
gus(7). However, the effects of SSRIs on the reflux
patients diagnosed GERD were included. At the
beginning, the study protocol was reviewed and
Although based upon the side effects of SSRIs
approved by the local ethics committee, in accor-
on gastrointestinal system mentioned above, no
dance with the ethical principles for human investi-
Timucin Aydogan, Mehmet Ali Eren et Al
gations, as outlined by the Second Declaration of
decreased with the treatments in both groups (both
Helsinki, and written informed consent was
p<0.001). Moreover, the numbers of the patient
who said the reflux symptoms improved were sig-
Exclusion criteria included a past history of
nificantly higher in Group 1 than in Group 2 espe-
gastrointestinal surgery, gastric and duodenal ulcer,
cially in the terms of patients who said “Completely
the concurrent presence of organic diseases includ-
ing cancer and unwillingness of questionnaire.
Discussion
typical symptoms (heatburn and/or regurtitation) ata frequency higher than twice a week and for a
The data of this study reveal that i) depression
period longer than 4 weeks(8,9). All participants in
and anxiety scores were decreased in both treatment
the current study were administered esomeprazole
group suggest us that the association between anxi-
40 milligram twice a day and sodium alginate 4 x
ety, depression and reflux; ii) reflux symptoms were
500 milligram for three months. Anxiety symptoms
not resolved in the citalopram group suggest us that
were measured using the Beck Anxiety Inventory
citalopram has worsening effect on reflux.
(BAI) and depressive symptoms were measured
The previous study by Jansson et al. demon-
with the Beck Depression Inventory (BDI), version
strated the correlation between the anxiety, depres-
II (10-12). Patients who had BAI score (BAS) > 15
sion and reflux symptoms and they found that 2.8
and/or BDI score (BDS) > 16 were treated addition-
times increased reflux symptoms in present of anxi-
ally with citalopram 10 milligram/day for three
ety and depression(3). Marti´N-Merino et al. found
months, which were classified as moderate-severe
an increased incidence of GERD among patients
depression and/or anxiety. Participants were divided
with depression(13). At the same time anxiety, but not
into two groups: Group 1 (n=35) treated with only
depression, has found to be independent factor for
esomeprazole + sodium alginate and Group 2
the determining of health care utilization in dyspep-
(n=35) treated with esomeprazole + sodium algi-
tic patients(4). Patients with GERD have impaired
nate + citalopram. At the end of the study patients
quality of life compared with general populations
were asked for the recovery of present reflux symp-
and psychological factors could affect the clinical
toms and categorized as i) Completely resolved, ii)
manifestations of reflux disease(14,15). We showed
Significantly reduced, iii) Slightly reduced and iv)
that treatment of reflux disease provided improve-
ment in depression and anxiety scores independentfrom anti-depressant treatment. Statistical analysis
SSRIs had a direct damaging effect on the gas-
trointestinal mucosa and related with the increased
All statistical analyses were performed using
prevalence of gastric mucosal damage(16,17).
SPSS 15.0 for Windows (SPSS, Chicago, IL, USA).
However, it has been showed that citalopram can
Continuous variables were expressed as mean ±
mitigate inflammation-induced exacerbation of gas-
standard deviation (SD) and categorical variables
tric ulcers and augment the gastric mucus barrier(18).
were expressed as percentages. Either χ2 test or
SSRIs augment the availability of physiologically
Student’s unpaired t-test were used to compare the
released 5-hydroxytryptamine (5-HT) which is a
categorical or continuous variables, respectively.
neurotransmitter in the enteric nervous system and
Paired t-test was used to analyze changes within the
play a key role in the control of gastrointestinal
groups. A two-sided p value < 0.05 was considered
motility(19,20). Acute effects of citalopram as a selec-
tive 5-HT reuptake inhibitor include decreasing ofbasal gastric tone, impairing gastric accommoda-
tion to a meal, enhancing gastric emptying of solidsand increasing the volume of nutrient drink ingest-
There were no significant differences in base-
ed before maximal satiation(20). Citalopram signifi-
line demographic features and clinical findings
cantly decreases the of mechanical and chemical
other than BDS and BAS between two groups
sensitivity the esophagus and SSRIs treatment may
(Table 2). BDS and BAS were significantly higher
be a reasonable and beneficial option for the hyper-
in Group 2 than in Group 1 at the beginning (both
p<0.001). BAS and BDS were significantly
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
classification of gastroesophageal reflux disease: a
known. We found that reflux symptoms were not
global evidence-based consensus. Am J Gastroenterol2006 Aug; 101(8): 1900-20.
resolved in citalopram treated group as well as
DeVault KR, Castell DO: American College of
other treatment group that not include citalopram.
Gastroenterology. Updated guidelines for the diagnosis
The side effects of citalopram related with gastroin-
and treatment of gastroesophageal reflux disease. Am J
testinal system especially on reflux disease seem to
Gastroenterol 2005 Jan; 100(1): 190-200.
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occur over the inhibition of 5-HT reuptake. As dis-
for measuring clinical anxiety: psychometric proper-
cussed above, citalopram may be a treatment option
ties. Journal of Consulting and Clinical Psychology
for hypersensitive esophagus. However, present
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J:
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An inventory for measuring depression. Arch Gen
esophagus because of lack of upper gastrointestinal
system endoscopy and 24 hour pHmeter. It is the
Beck AT, Steer RA, Garbin MG: Psychometric proper-ties of the Beck depression inventory: twenty-five years
most important limitation of our study. of evaluation. Clin Psychol Rev 1988; 8: 77-100.
MartÃn-Merino E, Ruigómez A, GarcÃa RodrÃguez LA,
Conclusion
Wallander MA, Johansson S: Depression and treatmentwith antidepressants are associated with the develop-ment of gastro-oesophageal reflux disease. Aliment
In the present study, the administration of
Pharmacol Ther 2010 May; 31(10): 1132-40.
citalopram to patients with GERD caused the distri-
Kamolz T, Velanovich V: Psychological and emotional
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aspects of gastroesophageal reflux disease. DisEsophagus 2002; 15(3): 199-203.
study provides further evidence for the relationship
Baker LH, Lieberman D, Oehlke M: Psychological dis-
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should be taken into account when managing
Am J Gastroenterol 1995 Oct; 90(10):1797-803.
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65--Health and Medical Supplies Solicitation Number: W90M7903630300Agency: Department of the ArmyOffice: National Guard BureauLocation: USPFO for Utah :Combined Synopsis/SolicitationSynopsis:Added: Mar 22, 2011 4:08 pmThis is a combined synopsis/solicitation for commercial items prepared in accordance with the format inSubpart 12.6, as supplemented with additional information included in this n
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