Can fluoxetine (Prozac) and brexpiprazole (Rexulti) be taken together?

From the Guidelines

Prozac (fluoxetine) and Rexulti (brexpiprazole) can be taken together, but it is crucial to exercise caution due to the potential risk of serotonin syndrome, a potentially life-threatening condition caused by elevated brain serotonin levels 1. When considering this combination, it's essential to understand that Prozac is a selective serotonin reuptake inhibitor (SSRI) antidepressant, while Rexulti is an atypical antipsychotic that can also affect serotonin levels. Some key points to consider when taking these medications together include:

• Potential side effects such as increased risk of drowsiness, dizziness, weight gain, and metabolic changes
• The need for close monitoring by a healthcare provider to adjust dosages as needed and minimize the risk of adverse effects
• The importance of reporting any unusual side effects, such as mental status changes, neuromuscular hyperactivity, or autonomic hyperactivity, which can be symptoms of serotonin syndrome 1 It's also important to note that the combination of Prozac and Rexulti should only be used under medical supervision, as the healthcare provider will need to weigh the potential benefits against the potential risks and monitor the patient's response to the treatment. Some of the factors that may influence the decision to use this combination include:
• The patient's medical history, including any history of seizure disorders or bleeding events
• The patient's current medications, including any other serotonergic agents or medications that may interact with Prozac or Rexulti
• The patient's ability to tolerate potential side effects and adhere to the prescribed treatment regimen 1

From the FDA Drug Label

• In the clinical studies examining the adjunctive use of brexpiprazole in the treatment of MDD, dosage was not adjusted for strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine).

1. 2 Drugs Having No Clinically Important Interactions with Brexpiprazole Based on pharmacokinetic studies, no dosage adjustment of brexpiprazole is required when administered concomitantly with CYP2B6 inhibitors (e.g., ticlopidine) or gastric pH modifiers (e.g., omeprazole). Additionally, no dosage adjustment for substrates of CYP2D6 (e.g., dextromethorphan), CYP3A4 (e.g., lovastatin), CYP2B6 (e.g., bupropion), BCRP (e.g., rosuvastatin), or P-gp (e.g., fexofenadine) is required when administered concomitantly with brexpiprazole.

Key Points:

• Fluoxetine (Prozac) is a strong CYP2D6 inhibitor.
• Brexpiprazole (Rexulti) can be administered without dosage adjustment in patients taking strong CYP2D6 inhibitors, such as fluoxetine.
• No dosage adjustment is required when administering brexpiprazole with fluoxetine.

2

From the Research

Combination of Prozac and Rexulti

• Prozac (fluoxetine) is a selective serotonin reuptake inhibitor (SSRI), while Rexulti (brexpiprazole) is an atypical antipsychotic with partial serotonin agonist activity.
• There is evidence to suggest that combining brexpiprazole with SSRIs, such as fluoxetine, can have a synergistic anti-depressive effect 3.
• A study found that the combination of brexpiprazole and fluoxetine showed a rapid antidepressant effect in a social defeat stress model, with the involvement of BDNF-TrkB signaling 4.
• Another study found that the combination of brexpiprazole with SSRIs, including fluoxetine, reduced immobility time in the forced swimming test in mice, indicating a synergistic antidepressant-like effect 3.

Safety Considerations

• However, it is essential to consider the potential risks of combining these medications, including the risk of serotonin syndrome, a potentially life-threatening condition 5.
• A case report described a patient who developed delayed-onset serotonin syndrome after ingesting a mixture of fluoxetine and other serotonergic agents, highlighting the need for caution when combining these medications 5.
• Additionally, fluoxetine has been associated with reversible cerebral vasoconstriction syndrome (RCVS), a rare but potentially serious condition 6.

Clinical Implications

• Clinicians should carefully evaluate the potential benefits and risks of combining Prozac and Rexulti, taking into account the individual patient's medical history and current medications.
• Close monitoring for signs of serotonin syndrome and other adverse effects is crucial when combining these medications 5, 6, 7.