Can Bupropion Cause Diarrhea?
Bupropion causes diarrhea significantly less often than SSRIs, making it a preferred choice when gastrointestinal side effects are a concern. In head-to-head trials, bupropion demonstrated a 69% lower risk of diarrhea compared to selective serotonin reuptake inhibitors 1, 2.
Comparative Incidence of Diarrhea
Bupropion versus SSRIs: Direct comparison trials show bupropion has a relative risk of 0.31 (95% CI 0.16 to 0.57) for diarrhea compared to SSRIs—meaning patients on bupropion are approximately three times less likely to experience diarrhea than those on sertraline, fluoxetine, or paroxetine 1.
Specific comparison with sertraline: In a 16-week double-blind trial, sertraline-treated patients experienced diarrhea significantly more frequently (p < 0.05) than bupropion SR-treated patients 2.
Clinical guideline context: The American College of Physicians' 2008 guideline on second-generation antidepressants confirms that sertraline has a higher rate of diarrhea than bupropion, citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, or venlafaxine 3.
Other Gastrointestinal Effects
While diarrhea is uncommon with bupropion, other gastrointestinal effects warrant consideration:
Nausea: Bupropion has a 40% lower risk of nausea compared to SSRIs (relative risk 0.6,95% CI 0.41 to 0.89), though nausea remains more common than diarrhea with this medication 1.
Constipation: The American College of Physicians notes constipation as one of the most commonly reported adverse events across second-generation antidepressants, including bupropion 3.
Rare severe reactions: One case report documented diarrhea as part of thrombotic thrombocytopenic purpura syndrome occurring 54 days after bupropion initiation, though this represents an extremely rare immune-mediated reaction rather than a typical side effect 4.
Clinical Implications
When selecting an antidepressant for patients with pre-existing gastrointestinal sensitivity or irritable bowel syndrome, bupropion offers a distinct advantage over SSRIs in terms of lower diarrhea risk 1, 2. The British Society of Gastroenterology guidelines on IBS management note that SSRIs can be effective gut-brain neuromodulators but require counseling about side effects—diarrhea being notably less problematic with bupropion 3.
For patients experiencing diarrhea on an SSRI, switching to bupropion or augmenting with bupropion (rather than adding another serotonergic agent) may reduce gastrointestinal side effects while maintaining antidepressant efficacy 3, 1.