Gastrointestinal Side Effects of Fluoxetine

Introduction to Gastrointestinal Side Effects

The American College of Physicians guidelines identify gastrointestinal disturbances as the most frequently reported adverse events with SSRIs, including fluoxetine 1, 2
Nausea and vomiting are the most common reasons for treatment discontinuation in efficacy studies 1, 2, 3
Diarrhea is a commonly reported side effect across all SSRIs 1, 2, 3
Constipation also occurs, though less frequently than with tricyclic antidepressants 1, 2

Fluoxetine increases serotonin concentration at nerve endings throughout the body, including the gastrointestinal tract 4, 5
Increased GI motility results from elevated serotonin levels, which can manifest as bloating, cramping, diarrhea, or altered bowel habits 4, 6
The American Gastroenterological Association specifically recommends against using SSRIs for irritable bowel syndrome because they did not significantly improve global symptoms or abdominal pain (RR 0.74; 95% CI 0.52-1.06), with the upper confidence interval suggesting possible symptom worsening 4, 6
Sertraline has higher rates of diarrhea than fluoxetine 1, 2
Venlafaxine has higher rates of nausea and vomiting than fluoxetine 1, 2
Mirtazapine has fewer GI side effects overall but causes increased appetite 1