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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
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.
Beck AT, Epstein N, Brown G, Steer RA: An inventory 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: study unable to exclude patient with hypersensitive 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.
Martín-Merino E, Ruigómez A, García Rodríguez 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 bution of recovery of the reflux symptoms. This 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- between citalopram and GERD. This relation tress in patients with gastroesophageal reflux disease.
should be taken into account when managing Am J Gastroenterol 1995 Oct; 90(10):1797-803.
depression in the patients with severe reflux symp- Takeuchi K, Tanaka A, Takahira Y, et al.: Selective sero-tonin reuptake inhibitors (SSRIs) aggravate antral ulcers induced by indomethacin in rat stomachs (abstract 337)Gastroenterology 2005; 128 (suppl 2): 48.
Yamamoto T, Abe K, Hattori K, Ishii T, Kuyama Y:High prevalence of gastroduodenal mucosal injury inpatients taking selective serotonin reuptake inhibitors. References
Saxena B, Singh S: Investigations on gastroprotective Dent J, El-Serag HB, Wallander MA, Johansson S: effect of citalopram, an antidepressant drug against Epidemiology of gastrooesophageal reflux disease: a stress and pyloric ligation induced ulcers. Pharmacol systematic review. Gut 2005; 54: 710-7.
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Martı´n-Merino E, Ruigo´mez A, Johansson S, Gershon MD, Tack J: The serotonin signaling system: Wallander M-A, Garcı´a-Rodrı´guez LA: Study of a from basic understanding to drug development for cohort of patients newly diagnosed with depression in functional GI disorders. Gastroenterology 2007; 132: general practice: prevalence, incidence, comorbidity and treatment patterns. Prim Care Companion J Clin Janssen P, Van Oudenhove L, Casteels C, et al.: The effects of acute citalopram dosing on gastric motor Jansson C, Nordenstedt H, Wallander MA, et al.: Severe function and nutrient tolerance in healthy volunteers. gastro-oesophageal reflux symptoms in relation to anxi- Aliment Pharmacol Ther 2011 Feb; 33(3): 395-402. ety, depression and coping in a population-based study.
Broekaert D, Fischler B, Sifrim D, Janssens J, Tack J: Aliment Pharmacol Ther 2007; 26: 683-91.
Influence of citalopram, a selective serotonin reuptake Hu WH, Wong WM, Lam CL, et al.: Anxiety but not inhibitor, on oesophageal hypersensitivity: a double- depression determines health careseeking behaviour in blind, placebo-controlled study. Aliment Pharmacol Chinese patients with dyspepsia and irritable bowel Ther 2006 Feb 1; 23(3): 365-70.
syndrome: a population-based study. AlimentPharmacol Ther 2002; 16: 2081-8. Avidan B, Sonnenberg A, Giblovich H, Sontag SJ:Reflux symptoms are associated with psychiatric dis-ease. Aliment Pharmacol Ther 2001; 15: 1907-12.
Itatsu T, Nagahara A, Hojo M, et al.: Use of selectiveserotonin reuptake inhibitors and upper gastrointesti-nal disease. Intern Med 2011; 50(7): 713-7. Viazis N, Karamanolis G, Vienna E, Karamanolis DG: Selective-serotonin reuptake inhibitors for the treat- ment of hypersensitive esophagus. Therap Adv Gastroenterol 2011 Sep; 4(5): 295-300. Department of Internal Medicine and Gastroenterology Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group: The Montreal definition and


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