Can I take fluoxetine (Prozac) with duloxetine (Cymbalta)?

From the Guidelines

No, you should not take Prozac (fluoxetine) with Cymbalta (duloxetine) together without medical supervision. These medications are both antidepressants that increase serotonin levels in the brain, and taking them together can lead to serotonin syndrome, a potentially serious condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or loss of consciousness. According to the American College of Physicians clinical practice guideline 1, second-generation antidepressants, including fluoxetine and duloxetine, should be selected based on adverse effect profiles, cost, and patient preferences.

Key Considerations

• Both medications work in similar ways - Prozac is a selective serotonin reuptake inhibitor (SSRI) while Cymbalta is a serotonin-norepinephrine reuptake inhibitor (SNRI).
• If you're currently taking one medication and your doctor is considering switching you to the other, they will typically recommend a washout period between medications, especially for Prozac which has a long half-life and can remain in your system for weeks.
• The American College of Physicians recommends that clinicians assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy 1.

Important Precautions

• Always consult with your healthcare provider before starting, stopping, or combining any antidepressant medications.
• Be aware of the potential for serotonin syndrome and seek medical attention immediately if you experience any symptoms.
• Regular monitoring of your condition and adjustment of your treatment plan as needed can help minimize the risks associated with taking these medications.

From the FDA Drug Label

Duloxetine delayed-release capsules and some medicines may interact with each other, may not work as well, or may cause serious side effects Especially tell your healthcare provider if you take: medicines used to treat mood, anxiety, psychotic or thought disorders, including tricyclics, lithium, buspirone, SSRIs, SNRIs or MAOIs Ask your healthcare provider for a list of these medicines if you are not sure.

The FDA drug label does not explicitly state that you can or cannot take Prozac (an SSRI) with Cymbalta (duloxetine, an SNRI). However, it does mention that duloxetine delayed-release capsules and some medicines may interact with each other, may not work as well, or may cause serious side effects, especially when taken with other medicines used to treat mood, anxiety, psychotic or thought disorders, including SSRIs.

• Key consideration: The label advises to tell your healthcare provider about all the medicines that you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
• Clinical decision: Given the potential for interaction, it is recommended to consult your healthcare provider before taking Prozac with Cymbalta to discuss the potential risks and benefits of this combination 2.

From the Research

Combination of Prozac and Cymbalta

• The combination of Prozac (fluoxetine), a selective serotonin reuptake inhibitor (SSRI), and Cymbalta (duloxetine), a serotonin-norepinephrine reuptake inhibitor (SNRI), may increase the risk of serotonin syndrome, a potentially fatal complication 3, 4.
• Serotonin syndrome is characterized by symptoms such as neuromuscular symptoms, altered thermoregulation, and altered mental status 4.
• The risk of serotonin syndrome may be increased when combining SSRIs and SNRIs, as both classes of medications enhance serotonin activity 3, 4.

Mechanism of Action

• Prozac (fluoxetine) works by inhibiting the reuptake of serotonin at the serotonin transporter, increasing serotonin levels in the synapse 5, 6.
• Cymbalta (duloxetine) works by inhibiting the reuptake of both serotonin and norepinephrine, increasing the levels of both neurotransmitters in the synapse 7.
• The combination of these two mechanisms of action may increase the risk of serotonin syndrome, as the enhanced serotonin activity may lead to excessive serotonin levels in the synapse 3, 4.

Adverse Effects

• The combination of Prozac and Cymbalta may also increase the risk of other adverse effects, such as gastrointestinal disturbances, headache, sedation, insomnia, and sexual dysfunction 5, 6.
• The risk-benefit analysis of combining these two medications should be carefully considered, taking into account the potential treatment effects, adverse effects, and dangers of the illness being treated 5.