Psychological Processes, Not Physiological Parameters, Are Most Important Contributors to Symptom Severity in Patients With Refractory Heartburn/Regurgitation Symptoms.

BACKGROUND & AIMS: Physiological and psychological factors have been found to influence esophageal symptom reporting. We aimed to evaluate which of these factors are associated with 3 reflux symptom severity outcomes (ie, Total Reflux, Heartburn, and Sleep Disturbance) through a traditional statistical and a complementary machine-learning approach. METHODS: Consecutive adult patients with refractory heartburn/regurgitation symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing past and current gastrointestinal and psychological health. In the traditional statistical approach, hierarchical general linear models assessed relationships of psychological and physiological variables (eg, total number of reflux episodes) with reflux severity scores. Mediation analyses further assessed pathways between relevant variables. In the machine-learning approach, all psychological and physiological variables were entered into 11 different models and cross-validated model performance was compared among the different models to select the best model. RESULTS: Three hundred ninety-three participants (mean [SD] age, 48.5 [14.1] years; 60% were female) were included. General psychological functioning emerged as an important variable in the traditional statistical approach, as it was significantly associated with all 3 outcomes and mediated the relationship between childhood trauma and both Total Reflux and Heartburn Severity. In the machine-learning analyses, general psychological variables (eg, depressive symptoms) were most important for Total Reflux and Sleep Disturbance outcomes, and symptom-specific variables, like visceral anxiety, were more influential for Heartburn Severity. Physiological variables were not significant contributors to reflux symptom severity outcomes in our sample across reflux classifications and statistical methodology. CONCLUSIONS: Psychological processes, both general and symptom-specific, should be considered as another important factor within the multifactorial processes that impact reflux symptom severity reporting across the reflux spectrum.

Psychological symptoms do not discriminate between reflux phenotypes along the organic-functional refractory GERD spectrum.

OBJECTIVE: Historically, psychological processes are associated with disorders at the functional end of the gastro-oesophageal reflux disease (GERD) spectrum. However, recent research suggests that psychological symptoms are relevant across the entire GERD spectrum. We aim to investigate whether psychological symptoms are associated with reflux phenotype (True GERD, Borderline GERD, reflux hypersensitivity, functional heartburn) along the GERD spectrum in a cohort of refractory reflux patients. DESIGN: Consecutive adult patients with refractory reflux symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing demographic, clinical and psychological information. Bayesian one-way analysis of variance assessed whether psychological variables differed across reflux phenotypes. Next, we applied multinomial and ordinal logistic regressions with clinical, demographic and psychological variables set as independent variables and reflux phenotype as the outcome variable. The complementary machine-learning approach entered all demographic, clinical and psychological variables into models, with reflux phenotype set nominally and ordinally. Cross-validated model performance was used to select the best model. RESULTS: 393 participants (mean (SD) age=48.5 (14.1); 60% female) were included. The Bayesian analyses found no difference in psychological variables across reflux phenotypes. Similarly, age, gender and proton pump inhibitor use were the only significant variables in the multinomial logistic regression and body mass index was significant in both regressions. Machine-learning analyses revealed poorly performing models with high misclassification rates (67-68%) in both models. CONCLUSION: Psychological symptoms do not differ between nor predict reflux phenotype membership in refractory reflux patients. Findings suggest that psychological symptoms are relevant across the spectrum of GERD, rather than specific to functional oesophageal disorders.

Gastroesophageal Reflux Disease-Functional Dyspepsia Overlap: Do Birds of a Feather Flock Together?

INTRODUCTION: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are 2 of the most prevalent upper gastrointestinal (GI) disorders in the Western world. Previous Rome definitions excluded patients with predominant heartburn from the definition of FD because they were considered to have GERD. However, more recent studies showed that heartburn and acid regurgitation are also common symptoms in patients with FD. The aim of this study is to provide an overview of the prevalence of overlap between GERD and FD, the underlying pathophysiology and implications for treatment. METHODS: A review of the literature was performed using the PubMed database, and a meta-analysis with random effects model was completed. RESULTS: This review showed considerable overlap between GERD and FD. A meta-analysis on the data included in this review showed 7.41% (confidence interval [CI]: 4.55%-11.84%) GERD/FD overlap in the general population, 41.15% (CI: 29.46%-53.93%) GERD with FD symptoms, and 31.32% (CI: 19.43%-46.29%) FD with GERD symptoms. Although numerous committees and consensus groups attempted to develop uniform definitions for the diagnosis of GERD and FD, various diagnostic criteria are used across studies and clinical trials (frequency, severity, and location of symptoms). Several studies showed that the overlap between GERD and FD can be explained by a shared pathophysiology, including delayed gastric emptying and disturbed gastric accommodation. DISCUSSION: For diagnoses of GERD and FD, uniform definitions that are easy to implement in population studies, easy to interpret for physicians, and that need to be well explained to patients to avoid overestimation or underestimation of true prevalence are needed. Both GERD and FD coexist more frequently than expected, based on coincidence, suggesting a potential pathophysiological link. More research is needed to explore the common GERD/FD overlap population to identify the underlying pathophysiological mechanisms, which may lead to a more effective therapeutic approach.

The Acute Effect of Hydroxychloroquine Sulfate on Hunger, the Plasma Concentration of Orexigenic Peptides and Hedonic Food Intake: A Pilot Study.

The direct infusion of bitter solutions in the gastrointestinal tract can reduce the secretion of orexigenic hormones and influence appetite and food intake. We aimed to explore whether oral ingestion of the bitter tastant hydroxychloroquine sulfate can exert similar effects. Ten lean adult women were included in this double-blind, randomized, two-visit, crossover study. After an overnight fast, each volunteer received film-coated tablets containing 400 mg of hydroxychloroquine sulfate (Plaquenil®) or placebo. Plasma-ghrelin, -motilin, -insulin and blood-glucose concentrations were determined every 10 min before and 30 min after feeding; appetite was scored every 10 min. Hunger scores were investigated with a special interest 50-60 min after the ingestion of hydroxychloroquine sulfate, right before a rewarding chocolate milkshake was offered to drink ad libitum. Compared with the placebo, hydroxychloroquine sulfate tended to reduce hunger at the time of interest (p = 0.10). No effect was found upon subsequent milkshake intake. Motilin plasma concentrations were unaltered, but acyl-ghrelin plasma concentrations decreased after the ingestion of hydroxychloroquine sulfate (t = 40-50; p < 0.05). These data suggest that the oral intake of hydroxychloroquine sulfate tablets reduces subjective hunger via a ghrelin-dependent mechanism but does not affect motilin release, hedonic food intake or insulin levels in healthy women.

Evaluating the impact of position, volume, and consistency on high-resolution esophageal manometry outcomes.

BACKGROUND: The Chicago classification primarily utilizes ten 5 mL liquid swallows in a supine position as the standard high-resolution esophageal manometry (HRM) protocol. HRM can be performed with varying volumes and consistencies and in an upright position. We aimed to determine the impact on HRM results by (1) position, (2) swallows of differing volume and consistency, and (3) perception of bolus passage. METHODS: HRM was performed in healthy volunteers (HV) with the following protocol of swallows: liquids 10 × 5 mL, 5 × 10 mL, and 3 × 10 mL multiple rapid swallows; applesauce 5 × 5 mL and 5 × 10 mL; and bread 5 × 2 × 2 cm and 5 × 4 × 4cm. HV rated difficulty of each swallow on a 5-point Likert scale. All HVs performed the protocol in supine position first and then in "semi-upright" (sitting 70 degrees in a bed) and "upright" (sitting in a chair) in a randomized order. KEY RESULTS: Thirty-seven HVs, median age 27 years, 64% female completed this study. Median distal contractile integral (DCI) and integrated relaxation pressure 4 s (IRP4) of 5 mL liquid swallows significantly differed (all p < 0.01) between position performed. Large volume swallows resulted in higher DCI and lower IRP4. IRP4 results were significantly increased for 2 × 2 cm pieces of bread compared to 5 mL water swallows. DCI results were higher for 2 × 2 cm pieces of bread compared to 5 mL water swallows. Distal latency was shorter in more upright positions. Among this cohort of HV, perceived difficulty of bolus passage was more likely to occur with solid boluses. CONCLUSIONS AND INFERENCES: The volume and consistency of a swallow and the position it is performed in, significantly alter HRM metrics. Interpretation of HRM studies should incorporate different normative values which are specific to the position and bolus type.

The impact of endoscopic lung volume reduction on physical activity coaching in patients with severe emphysema.

Introduction: Endoscopic lung volume reduction (ELVR) aims to improve pulmonary function in severe emphysema. Physical activity (PA) coaching is expected to improve daily life PA. When improving ventilatory constrains in severe COPD, a better response to PA coaching is expected. The present study investigated the impact of PA coaching in addition to ELVR in severe emphysema. Methods: Patients allocated, based on fissure integrity, in the ELVR or no-ELVR cohort, received the PA coaching intervention with a step counter and smartphone application from 3 to 6 months follow-up. The primary end-point of this research question was the change in daily step count from baseline to 6 months follow-up compared between the ELVR and no-ELVR cohort. The secondary end-points were time spent in moderate to vigorous PA, movement intensity and patient-reported experience with PA between ELVR and no-ELVR. Results: At 6 months, PA in both ELVR+coaching (1479±460 steps·day-1; p=0.001) and no-ELVR+coaching (1910±663 steps·day-1; p=0.004) improved within group, without significant between-group differences (-405±781 steps·day-1; p=0.60). Patients in the ELVR group tended to experience less difficulty with PA compared to no-ELVR+coaching (7±4 points, p=0.08). Conclusion: We found that PA coaching is feasible and can help to enhance PA in patients with severe emphysema. Improving the ventilatory capacity through ELVR is not a prerequisite for a successful coaching intervention to increase objectively measured PA, although it alleviates patients' experienced difficulty with PA in those with severe COPD.

Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial.

Psychological stress negatively affects the intestinal barrier function in animals and humans. We aimed to study the effect of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress-markers during public speech. Healthy students were randomized to L. rhamnosus-containing (test) or acidified (placebo) milk consumed twice daily for 4 weeks, with 46 subjects per treatment group. Small intestinal permeability was quantified by a 2 h urinary lactulose-mannitol ratio (LMR, primary outcome), fractional excretion of lactulose (FEL) and mannitol (FEM). Salivary cortisol, State-Trait Anxiety Inventory (STAI) and Perceived Stress scores (PSS) were collected. No between-treatment differences were found for LMR (p = .71), FEL or FEM. Within-treatment analyses showed similar LMR and FEL but a stress-induced increase of FEM with the placebo (p < .05) but not test product. Despite a similar increase in salivary cortisol, the stress-induced increase in STAI was significantly lower with the test product vs. placebo (p = .01). Moreover, a stress-preventative effect of the probiotic was found for PSS and more pronounced in subjects with high stress-induced cortisol (p = .01). While increased FEM was mediated by salivary cortisol levels, the effect of the test product on subjective stress was not mediated by changes in FEM. No serious adverse events occurred. In conclusion, we demonstrated that L. rhamnosus CNCM I-3690 prevented stress-induced hyperpermeability to mannitol. Subjective but not objective stress-markers were reduced with L. rhamnosus vs. placebo, suggesting anxiolytic effects, which were independent of barrier stabilization and attractive for the reduction of stress in both health and disease. Clinicaltrials.gov, number NCT03408691.

The effect of an air purifier on aerosol generation measurements during clinical motility testing.

BACKGROUND: Aerosol spread is key to interpret the risk of viral contamination during clinical procedures such as esophageal high-resolution manometry (HRM). Installing an air purifier seems a legitimate strategy, but this has recently been questioned. METHODS: Patients undergoing an HRM procedure at the Leuven University Hospital were included in this clinical study. All subjects had to wear a surgical mask which was only lowered beneath the nose during the placement and removal of the nasogastric catheter. The number of aerosol particles was measured by a Lasair® II Particle Counter to obtain data about different particles sizes: 0.3; 0.5; 1.0; 3.0; 5.0; and 10.0 µm. Measurements were done immediately before the placement and the removal of the HRM catheter, and one and 5 min after. A portable air purifier with high-efficiency particle air filters was installed in the hospital room. KEY RESULTS: Thirteen patients underwent a manometry examination. The amount of 0.3 µm-sized particles was unaffected during the whole procedure. The larger particle sizes (1.0; 3.0; 5.0; and 10.0 µm) decreased when the catheter was positioned, but not 0.5 µm. During the HRM measurements itself, these numbers decreased further. Yet, 1 min after catheter removal a significant elevation of particles was seen, which did not recover within 5 min. CONCLUSIONS & INTERFERENCES: Based on this study, there is no evidence that filtration systems reduce aerosol particles properly during a clinical investigation.

The gastro-sphincteric pressure gradient: A new parameter to diagnose a rumination episode.

BACKGROUND: Rumination is defined as the repetitive, effortless regurgitation of recently ingested food into the mouth. These episodes are preceded by a rise in intragastric pressure (IGP) and mainly occur postprandially. IGP peaks >30 mmHg have been proposed as a cutoff to differentiate rumination from reflux events. In clinical practice, we observed that this cutoff, which does not consider esophagogastric junction (EGJ) resistance, is not always reached. METHODS: We studied 27 patients with rumination syndrome [age: 43.6, 59% female] and 28 gastro-esophageal reflux disease patients [age: 45.9, 54% female]. For each rumination episode, reflux event, transient lower esophageal sphincter relaxation (TLESR), or straining without regurgitation, the following parameters were registered: maximal IGP, IGP, and EGJ pressure preceding the respective episodes. We also quantified the gastro-sphincteric pressure gradient (GSPG) prior to the respective episodes. KEY RESULTS: Five reflux episodes were characterized by a maximal IGP >30 mmHg. In 28% of the rumination episodes, the IGP peak did not exceed 30 mmHg. Median GSPG was positive for rumination episodes and significantly higher compared with TLESRs, reflux episodes, and straining without regurgitation (7 [3-13] vs. 0 [-1-0] vs. 0 [-1-0] vs. -9 [-13--2]; p < 0.0001). CONCLUSIONS & INTERFERENCES: Applying the proposed cutoff of 30 mmHg, 28% of the rumination episodes were missed. We found that the GSPG differentiates between rumination (positive GSPG), TLESRs and reflux events (GSPG around 0), and straining without regurgitation (negative GSPG). We propose a GSPG value ≥2 mmHg to distinguish rumination from reflux episodes, TLESRs, and straining without regurgitation.

The bitter tastant denatonium benzoate has no influence on the number of transient lower esophageal sphincter relaxations in health.

BACKGROUND: Administration of a bitter compound can alter the intragastric pressure (IGP) after a meal. Additionally, a negative correlation between IGP and the number of transient lower esophageal sphincter relaxations (TLESRs) has been demonstrated. However, the effect of a bitter tastant on the number of TLESRs and subsequent reflux episodes has never been investigated and it is unclear whether bitter food items should be avoided in gastro-esophageal reflux disease. We hypothesize that bitter administration in healthy volunteers (HVs) will lead to an increase in the number of TLESRs. METHODS: After an overnight fast, 20 female HVs (36 years [21-63]) underwent a high-resolution impedance manometry (HRiM) measurement. After placement of the HRiM probe, 0.1 ml/kg of a 10 mM denatonium benzoate solution (bitter) or an identical volume of water (placebo) was administered directly into the stomach. The number of TLESRs and reflux episodes was quantified 30 min before and 2 h after consumption of a high caloric meal. KEY RESULTS: There was no significant difference in the number of TLESRs or reflux episodes between the bitter and placebo condition. Additionally, no differences were observed in the nature (gas or liquid) and extent of reflux events. Lower esophageal sphincter pressures dropped significantly in the first postprandial hour to start recovering slowly back to baseline values during the second postprandial hour (p < 0.0001), without any difference between both conditions. CONCLUSIONS & INTERFERENCES: Administration of the bitter tastant denatonium benzoate has no influence on the number of TLESRs or reflux episodes.

Management of Ineffective Esophageal Hypomotility.

Esophageal hypomotility in general and especially ineffective esophageal motility according to the Chicago criteria of primary motility disorders of the esophagus, is one of the most frequently diagnosed motility disorders on high resolution manometry and results in a large number of patients visiting gastroenterologists. Most patients with esophageal hypomotility present with gastroesophageal reflux symptoms or dysphagia. The clinical relevance of the motility pattern, however, is not well established but seems to be correlated with disease severity in reflux patients. The correlation with dysphagia is less clear. Prokinetic agents are commonly prescribed as first line pharmacologic intervention to target esophageal smooth muscle contractility and improve esophageal motor functions. However, the beneficial effects of these medications are limited and only confined to some specific drugs. Serotonergic agents, including buspirone, mosapride and prucalopride have been shown to improve parameters of esophageal motility although the effect on symptoms is less clear. Understanding on the complex correlation between esophageal hypomotility and esophageal symptoms as well as the limited evidence of prokinetic agents is necessary for physicians to appropriately manage patients with Ineffective Esophageal Motility (IEM).

The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health.

BACKGROUND: Esophageal hypersensitivity is considered an important pathophysiological mechanism in refractory gastroesophageal reflux disease (GERD) patients. Serotonin (5-HT) plays an important role in the regulation of GI (gastrointestinal) secretion, motility and sensitivity. Previous studies found that altered 5-HT availability has no clear effects on esophageal/GI sensations. Our aim was therefore to investigate the role of 5-HT in esophageal sensitivity in healthy volunteers (HV). METHODS: Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 3 different placebo-controlled studies. In the first study, the effect of citalopram (40 mg; 5-HT reuptake inhibitor; intravenous) was investigated (n = 14). In the second study, the effect of buspirone (20 mg; 5HT1A agonist; oral) was investigated (n = 10). In the third study, acute tryptophan depletion (ATD) was used to decrease 5-HT levels to investigate the effect of reduced 5-HT availability on esophageal sensitivity (n = 15). KEY RESULTS: No difference was observed in esophageal sensitivity after the administration of citalopram or buspirone (all p > 0.06). In contrast, pain perception threshold to chemical stimulation was increased after ATD (p = 0.017, Cohen's d+ = 0.67). No effect was found on the first perception or pain tolerance threshold. ATD had no influence on esophageal sensitivity to thermal, mechanical, and electrical stimulation compared with placebo. CONCLUSIONS AND INFERENCES: ATD, which induces 5-HT depletion, significantly decreased pain perception threshold during chemical stimulation, without affecting sensitivity to mechanical, thermal, or electrical stimulation. These findings confirm the involvement of 5-HT in the control of esophageal acid sensitivity, but identifying the receptors involved requires more ligands and studies.

Codeine induces increased resistance at the esophagogastric junction but has no effect on motility and bolus flow in the pharynx and upper esophageal sphincter in healthy volunteers: A randomized, double-blind, placebo-controlled, cross-over trial.

BACKGROUND: Chronic opioid use can induce esophageal dysfunction with symptoms resembling achalasia and a manometric pattern of esophagogastric junction-outflow obstruction (EGJ-OO). However, the effect of opioids in acute setting on pharyngeal function and esophageal body contractility has not been investigated. METHODS: After positioning the high-resolution impedance manometry (HRiM) catheter, codeine (60 mg) or placebo (glucose syrup) was infused intragastrically. Forty-five minutes post-infusion, participants received liquid, semi-solid, and solid boluses to assess esophageal and pharyngeal function. HRiM analysis was performed adhering to the Chicago classification v3.0. (CC v3.0). Pressure flow analysis (PFA) for the esophageal body and the pharynx was performed using the SwallowGateway™ online platform. KEY RESULTS: Nineteen healthy volunteers (HV) [5 male; age 38.3] were included. After codeine administration, higher integrated relaxation pressure 4 s values resulted in significantly reduced deglutitive EGJ relaxation and distal latency was significantly shorter. Distal contractility was similar in both conditions. Bolus flow resistance at the EGJ and distention pressures increased significantly after codeine infusion. Based on CC v3.0, acute infusion of codeine induced EGJ-OO in six HV (p = 0.0003 vs. placebo). Codeine administration induced no significant alterations in any of the pharyngeal PFA metrics. CONCLUSIONS & INFERENCES: In HV, acute administration of codeine increased bolus resistance at the EGJ secondary to induced incomplete EGJ relaxation leading to major motility disorders in a subset of subjects including EGJ-OO. However, an acute single dose of codeine did not affect motility or bolus flow in pharynx and UES. ClinicalTrials.gov number, NCT03784105.

Acute administration of fructans increases the number of transient lower esophageal sphincter relaxations in healthy volunteers.

INTRODUCTION: Dietary measures are often advised to patients with gastro-esophageal reflux disease (GERD). Fermentable Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs) induce lower gastrointestinal (GI) symptoms. However, their effects on esophageal motility, including transient lower esophageal sphincter relaxations (TLESRs), reflux events and GERD symptoms are unknown. We investigated the effect of acute administration of two FODMAPs, fructose, and fructans, on the number of TLESRs, reflux episodes and symptom perception in healthy volunteers (HVs). MATERIALS: After an overnight fast, 20 HVs (10 males; 32.6 ± 2.8 years) underwent a high-resolution impedance manometry. The number of TLESRs and reflux episodes was quantified during five hours after consumption of a high-caloric meal (740 kcal) enriched with 40 g of either fructose, fructans or glucose (as placebo). Results were analyzed using mixed models. RESULTS: There was a trend for a change in the number of TLESRs between the three conditions (P = .06). Post hoc analysis revealed a trend toward a higher number of TLESRs in the fructan condition compared with placebo (Pcorr  = .06). Acute administration of fructose did not influence the number of TLESRs. The total number of reflux events was not affected by either FODMAP condition. Lower esophageal sphincter (LES) pressures dropped significantly in the first postprandial hour to recover slowly back to baseline values (P < .0001), without any difference in LES pressure between the three conditions. CONCLUSION: Ingestion of fructans increased the number of TLESRs slightly compared with placebo. The effect of FODMAPs such as fructans or a low FODMAP diet on reflux parameters in GERD patients remains to be investigated.

A survey on the impact of the COVID-19 pandemic on motility and functional investigations in Europe and considerations for recommencing activities in the early recovery phase.

BACKGROUND: The COVID-19 pandemic, declared by WHO on March 13, 2020, had a major global impact on the healthcare system and services. In the acute phase, the presence of the SARS-CoV-2 virus in the aerodigestive tract limited activities in the gastroenterology clinic and procedures to emergencies only. Motility and function testing was interrupted and as we enter the recovery phase, restarting these procedures requires a safety-focused approach with adequate infection prevention for patients and healthcare professionals. METHODS: We summarized knowledge on the presence of the SARS-CoV-2 virus in the aerodigestive tract and the risk of spread with motility and functional testing. We surveyed 39 European centers documenting how the pandemic affected activities and which measures they are considering for restarting these measurements. We propose recommendations based on current knowledge as applied in our center. RESULTS: Positioning of catheters for gastrointestinal motility tests carries a concern for aerosol-borne infection of healthcare workers. The risk is low with breath tests. The surveyed centers stopped almost all motility and function tests from the second half of March. The speed of restarting and the safety measures taken varied highly. CONCLUSIONS AND INFERENCES: Based on these findings, we provided recommendations and practical relevant information for motility and function test procedures in the COVID-19 pandemic era, to guarantee a high-quality patient care with adequate infection prevention.

Effect of citalopram on esophageal motility in healthy subjects-Implications for reflux episodes, dysphagia, and globus.

BACKGROUND: Drugs such as citalopram, "targeting" the serotonin pathway, can alter esophageal mechano-chemical sensitivity and gastrointestinal motility. The aim of this study was to clarify the effect of citalopram on esophageal motility and sphincter function, transient lower esophageal sphincter relaxations (TLESRs), and reflux events. METHODS: Sixteen healthy volunteers (HV) receiving 20 mg citalopram or placebo intravenously, in a randomized cross-over fashion, underwent two high-resolution impedance manometry studies involving liquid swallows and a high-fat, high-caloric meal. Manometric, reflux, and symptom-related parameters were studied. KEY RESULTS: A lower distal contractile integral was recorded under citalopram, compared with placebo (P = 0.026). Upper esophageal sphincter (UES) resting pressure was significantly higher after citalopram administration throughout the study (P < 0.05, all periods). Similarly, the UES postswallow mean and maximum pressures were higher in the citalopram condition (P < 0.0001, in both cases) and this was also the case for the 0.2 s integrated relaxation pressure (P = 0.04). Esophagogastric junction resting pressures in the citalopram visit were significantly higher during swallow protocol, preprandial period, and the first postprandial hour (P < 0.05, in all cases). TLESRs and total reflux events were both reduced after citalopram infusion (P = 0.01, in both cases). During treatment with citalopram, five participants complained about globus sensation (P = 0.06). This citalopram-induced globus was associated with higher UES postswallow mean and maximum pressure values (P = 0.01 and P = 0.04, respectively). CONCLUSIONS AND INFERENCES: Administration of citalopram exerts a diversified response on esophageal motility and sphincter function, linked to clinically relevant phenomena: a reduction in postprandial TLESRs and the induction of drug-induced globus.