Effect of nortriptyline on brain responses to painful esophageal acid infusion in patients with non‐erosive reflux disease

Forcelini, Cassiano Mateus; Tomiozzo, José Carlos; Farré, Ricard; Oudenhove, Lukas Van; Callegari-Jacques, Sídia M.; Ribeiro, Mário; Madalosso, Ben Hur; Fornari, Fernando

doi:10.1111/nmo.12251

Cited by 22 publications

(16 citation statements)

References 51 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two studies reported a beneficial effect of antidepressant therapy, 26,29 whereas 1 published study and 1 conference abstract reported no benefit of nortriptyline on heartburn scores. 27,28 Differences in medication and patient selection between these studies may explain the observed differences. Both negative studies used nortriptyline, a TCA, whereas the positive studies used citalopram or fluoxetine, both SSRIs.…”

Section: Discussionmentioning

confidence: 92%

“…[17][18][19][20][21][22][23][24] For the treatment of heartburn this percentage ranged from 23% to 61%. [26][27][28][29] Unfortunately, considerable differences between the selected studies regarding the patient definition, outcome definition, and the method of symptom analysis hampered the meta-analysis of the data presented.…”

Section: Discussionmentioning

confidence: 97%

“…[26][27][28][29] Viazis et al 26 identified 75 patients with a hypersensitive esophagus among a group of 252 patients with proton pump inhibitor (PPI)-refractory reflux symptoms. Although these patients showed physiological acid exposure during a 24-hour pH-impedance measurement, Ten milligrams during the first week, followed by 25 mg during weeks 2 and 3.…”

Section: Heartburn In Gastroesophageal Reflux Disease Patientsmentioning

confidence: 99%

“…Besides these 2 positive studies, we also retrieved 2 studies that reported negative results. In a study by Forcelini et al, 28 20 patients with nonerosive reflux disease were evaluated after treatment with nortriptyline (10 mg/d for 1 week, followed by 25 mg/d for 2 weeks) and placebo in a cross-over randomized fashion. Both nortriptyline and placebo significantly improved symptoms assessed using a validated heartburn questionnaire.…”

Section: Heartburn In Gastroesophageal Reflux Disease Patientsmentioning

confidence: 99%

See 3 more Smart Citations

Effects of Antidepressants in Patients With Functional Esophageal Disorders or Gastroesophageal Reflux Disease: A Systematic Review

Weijenborg

Schepper

Smout

et al. 2015

Clinical Gastroenterology and Hepatology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 97%

Section: Heartburn In Gastroesophageal Reflux Disease Patientsmentioning

confidence: 99%

Section: Heartburn In Gastroesophageal Reflux Disease Patientsmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Antidepressants in Patients With Functional Esophageal Disorders or Gastroesophageal Reflux Disease: A Systematic Review

Weijenborg

Schepper

Smout

et al. 2015

Clinical Gastroenterology and Hepatology

View full text Add to dashboard Cite

“…Th e results of this study suggest that the fi rst two are not achieved with a TCA. A similar conclusion stems from a small fMRI study of nortriptyline vs. placebo for non-erosive refl ux disease ( 8 ). Even though the TCA was superior to placebo in decreasing the brain's physiological response to esophageal acid infusion, it had no advantage over placebo with respect to heartburn perception.…”

Section: Conflict Of Interestmentioning

confidence: 76%

Editorial: Low-Dose Tricyclics for Esophageal Hypersensitivity: Is It All Placebo Effect?

Keefer

Kahrilas

2016

American Journal of Gastroenterology

View full text Add to dashboard Cite

Limsrivilai et al. report on a randomized control trial (RCT) testing the effi cacy of imipramine for treating esophageal hypersensitivity and functional heartburn, the fi rst RCT to test this therapy in this indication. Among 43 functional heartburn and esophageal hypersensitivity patients randomized to treatment with 25 mg qhs imipramine and 40 randomized to matched placebo, the response rates, judged by a 50% reduction in gastroesophageal refl ux disease symptoms, were 37.2% and 37.5%, respectively, with no observed difference between patients with hypersensitivity and those with functional heartburn. On the positive side, imipramine treatment was associated with improvement in quality of life as assessed by total SF-36 score. Although negative at fi rst glance, there are several important lessons from this study: (i) low-dose tricyclic is suffi cient in these patients; (ii) proton pump inhibitors can (and should) be discontinued when they are ineffective; and (iii) distinguishing between functional heartburn and esophageal hypersensitivity is of unclear clinical relevance. Am J Gastroenterol 2016; 111:225-227; doi: 10.1038/ajg.2016 In this issue of the Journal, Limsrivilai et al.( 1 ) report on a long overdue randomized control trial (RCT) testing the effi cacy of imipramine for treating esophageal hypersensitivity and functional heartburn. To our knowledge, this is the fi rst RCT to test this therapy in this indication, despite it having become the bedrock of expert recommendations for managing this challenging set of patients ( 2 ). Among 43 functional heartburn and esophageal hypersensitivity patients randomized to treatment with 25 mg qhs imipramine and 40 randomized to matched placebo, the response rates, judged by a 50% reduction in gastro esophageal refl ux disease (GERD) symptoms, were 37.2% and 37.5%, respectively, basically, within a rounding error of each other. On the positive side, those treated with imipramine were more likely to experience improvement in quality of life (QOL) as assessed by total SF-36 score. To be sure, a 37% response rate is not bad when treating functional disorders, but is this really all placebo eff ect?Although we tend to dismiss placebo response as simply a confounder in clinical trials, that may not be the best slant on it. Aft er all, if a therapy achieved a 37% response rate in patients who had been poorly responsive to proton pump inhibitors (PPIs), and they achieved that along with discontinuing the PPI, that is notable. Th is placebo response rate is on the high side of that observed in other GERD trials (PPIs, H 2 receptor antagonists, so on), estimated at about 18%, but within the reported range of 3-47% ( 3 ). Perhaps, some of the placebo benefi t was attributable to dietary and/or lifestyle modifi cations subconsciously adopted in conjunction with participating in a clinical trial or, perhaps, to the comforting eff ects of the concerned engagement by study personnel but, regardless, there is a lesson in this; sometimes, less is more. Th is adage appl...

show abstract

Recent Advances in the Pharmacological Management of Gastroesophageal Reflux Disease

Kung

Hsu

et al. 2017

Dig Dis Sci

View full text Add to dashboard Cite

The management of proton pump inhibitor-refractory GERD (rGERD) is a challenge in clinical practice. Since up to one-third of patients with typical GERD symptoms (heartburn and/or acid regurgitation) are not satisfied with proton pump inhibitor (PPI) therapy, new drug development targeting different pathophysiologies of GERD is imperative. At present, no other drugs serve as a more potent acid suppression agent than PPIs. As an add-on therapy, histamine type-2 receptor antagonists, alginates, prokinetics and transient lower esophageal sphincter relaxation inhibitors have some impact on the subgroups of rGERD, but greater effectiveness and fewer adverse effects for widespread use are required. Visceral hypersensitivity also contributes to the perception of GERD symptoms, and neuromodulators including antidepressants play a role in this category. Esophageal pH-impedance monitoring helps to distinguish functional heartburn from true GERD, and psychologic medication and cognitive behavior therapy are further therapy options instead of PPIs.

show abstract

Effect of nortriptyline on brain responses to painful esophageal acid infusion in patients with non‐erosive reflux disease

Abstract: Nortriptyline decreased the brain response to esophageal acid infusion more markedly than placebo, but without clinical significance.

Cited by 22 publications

References 51 publications

Effects of Antidepressants in Patients With Functional Esophageal Disorders or Gastroesophageal Reflux Disease: A Systematic Review

Effects of Antidepressants in Patients With Functional Esophageal Disorders or Gastroesophageal Reflux Disease: A Systematic Review

Editorial: Low-Dose Tricyclics for Esophageal Hypersensitivity: Is It All Placebo Effect?

Recent Advances in the Pharmacological Management of Gastroesophageal Reflux Disease

Contact Info

Product

Resources

About