Can Pristiq (Milnacipran) Cause Nausea and Diarrhea?
Yes, milnacipran commonly causes both nausea and diarrhea as gastrointestinal side effects, with nausea being the most frequently reported adverse event in clinical trials. 1
Evidence from Clinical Trials
Nausea is the most common adverse event reported in milnacipran recipients during fibromyalgia treatment trials, occurring frequently enough to be the leading side effect across multiple studies. 1
Gastrointestinal disturbances including nausea have been documented in clinical practice, though they occurred as isolated events in some cases and required treatment with antiemetics like metopimazine. 2
In a case report, a patient developed diarrhea and nausea after starting milnacipran 50 mg twice daily, which resolved after discontinuation of the medication. 3
Comparison to Other Antidepressants
Milnacipran belongs to the class of serotonin-norepinephrine reuptake inhibitors (SNRIs), and gastrointestinal side effects are frequently observed across all second-generation antidepressants in patients with major depressive disorder. 4
The gastrointestinal side effects of milnacipran appear to be related to its mechanism of action as a selective serotonin and norepinephrine reuptake inhibitor. 1
Clinical Management Considerations
Most adverse events with milnacipran are mild to moderate in severity, which means these gastrointestinal symptoms, while common, are typically manageable. 1
In clinical practice studies, milnacipran was well tolerated by the majority of patients (18 out of 28), with side effects leading to withdrawal in only 2 cases. 2
When gastrointestinal disturbances do occur, symptomatic treatment with antiemetics can be considered for nausea management. 2
Important Safety Context
Be aware that when combined with other serotonergic medications, milnacipran can contribute to serotonin toxicity, which presents with diarrhea and nausea among other symptoms including restlessness, increased heart rate, and elevated blood pressure. 3
The gastrointestinal symptoms resolved within one day after discontinuation of milnacipran in documented cases. 3