What is the relationship between nausea and fluoxetine (Prozac)?

From the Guidelines

Nausea is a common side effect of Prozac (fluoxetine), and to manage it, taking the medication with food, especially in the morning, is recommended. The evidence from 1 suggests that nausea is one of the possible side effects of selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, and that it can be mitigated by taking the medication with food. Starting with a lower dose, such as 5-10mg daily, and gradually increasing to the therapeutic dose, typically 20mg daily, can also help reduce nausea 1.

Managing Nausea

To minimize nausea, consider the following:

• Take Prozac with food, particularly in the morning with breakfast
• Start with a lower dose and gradually increase to the therapeutic dose
• If nausea persists or is severe, temporary use of over-the-counter antiemetics like ginger supplements (250mg four times daily) or prescription options such as ondansetron (4-8mg as needed) may help
• Do not stop taking Prozac abruptly, as this can cause discontinuation symptoms

Mechanism of Nausea

Nausea occurs because Prozac increases serotonin levels not only in the brain but also in the gut, where serotonin receptors can trigger the nausea response. The evidence from 1 and 1 highlights the importance of considering the potential side effects of SSRIs, including nausea, when prescribing these medications. If nausea remains intolerable despite these measures, consulting a healthcare provider about switching to a different antidepressant with potentially fewer gastrointestinal side effects may be necessary.

From the FDA Drug Label

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea)

The most common signs and symptoms associated with non–fatal overdosage were seizures, somnolence, nausea, tachycardia, and vomiting.

• Nausea is a symptom of serotonin syndrome and a common sign of non-fatal overdosage of fluoxetine 2 2.

From the Research

Nausea and Prozac

• Nausea is a common side effect associated with the use of antidepressants, including Prozac (fluoxetine) 3, 4, 5.
• A systematic review and meta-analysis found that all considered antidepressants, including fluoxetine, showed higher rates of gastrointestinal side effects, such as nausea and vomiting, compared to placebo 3.
• Another study compared the safety and side-effect profiles of four selective serotonin reuptake inhibitor antidepressants, including fluoxetine, and found that nausea/vomiting was the most frequent clinical reason for stopping treatment and the most frequently reported clinical event 5.
• Fluoxetine has been shown to be effective in treating major depressive disorder, but it can cause gastrointestinal disturbances, including nausea, as a side effect 4, 6.
• The incidence of nausea and vomiting associated with fluoxetine is comparable to other selective serotonin reuptake inhibitors, such as sertraline and paroxetine 5.

Comparison with Other Antidepressants

• A comparative effectiveness review of second-generation antidepressants found that fluoxetine, sertraline, and paroxetine had similar side effect profiles, including gastrointestinal side effects such as nausea 6.
• Another study found that fluvoxamine had a higher incidence of side effects, including nausea, compared to fluoxetine, sertraline, and paroxetine 5.
• Mirtazapine was found to have fewer side effects on the gut, including nausea, compared to other antidepressants 3.

Treatment of Nausea

• A randomized controlled trial compared the efficacy of ondansetron, metoclopramide, and placebo in treating nausea and vomiting in adult emergency department patients, but did not specifically study the use of Prozac or other antidepressants in treating nausea 7.
• The study found that ondansetron and metoclopramide were effective in reducing nausea severity, but the differences from the placebo group did not reach significance 7.