Which SSRIs Cause GERD
SSRIs do not directly cause GERD, but escitalopram and sertraline are associated with the highest rates of gastrointestinal side effects including nausea, vomiting, and abdominal discomfort that may mimic or exacerbate reflux symptoms. 1
Evidence from Gastrointestinal Side Effect Profiles
The most comprehensive analysis of antidepressant gastrointestinal effects demonstrates that among SSRIs:
Escitalopram and sertraline showed the highest rates of GI adverse effects, being associated with nausea/vomiting, diarrhea, abdominal pain, dyspepsia, anorexia, and dry mouth (but not constipation or increased appetite). 1
Citalopram was specifically reported in a case series to cause persistent nausea and gastric reflux symptoms that required addition of omeprazole for management. 2
The adverse drug reaction probability assessment indicated a probable relationship (Naranjo score 7/12) between SSRI initiation and GERD symptom presentation. 2
Mechanism: SSRIs vs. True GERD Causation
Important distinction: SSRIs do not cause GERD through the same mechanism as tricyclic antidepressants (which relax the lower esophageal sphincter via anticholinergic effects). 3, 2
SSRIs increase gastrointestinal motility by increasing serotonin concentration at nerve endings, which can accelerate transit and cause upper GI symptoms. 4, 5
These medications have no demonstrated impact on visceral sensation or lower esophageal sphincter tone. 4, 5
The symptoms patients experience are primarily nausea, dyspepsia, and abdominal discomfort rather than true reflux esophagitis. 1
Clinical Context from Guidelines
The American Gastroenterological Association recommends against using SSRIs for irritable bowel syndrome and related visceral disorders because they did not significantly improve symptoms (RR 0.74; 95% CI 0.52-1.06), with the upper confidence interval suggesting possible symptom worsening. 4
Paradoxical Therapeutic Use
Despite causing GI side effects, citalopram has been used successfully to treat hypersensitive esophagus (a condition where patients have reflux symptoms without true acid exposure), suggesting SSRIs modulate symptom perception rather than causing structural GERD. 6
- In refractory GERD patients with functional heartburn (normal acid exposure), paroxetine achieved symptom relief in 67% (14/21 patients). 7
Critical Clinical Pitfall
Do not confuse SSRI-induced upper GI symptoms with true GERD. If a patient develops reflux-like symptoms on SSRIs, consider:
The symptoms are likely medication side effects (nausea, dyspepsia) rather than acid-mediated esophageal injury. 1, 2
Adding a proton pump inhibitor may help symptomatically but does not address the underlying SSRI effect. 2
Switching to mirtazapine should be considered, as it has the fewest GI side effects among antidepressants (only associated with increased appetite). 1