From the Guidelines
Combining Contrave (naltrexone/bupropion) with Prozac (fluoxetine) is generally not recommended due to potential serious drug interactions, including an increased risk of serotonin syndrome and seizures, as both medications affect brain chemicals like serotonin and norepinephrine 1.
Key Considerations
- The use of Contrave and Prozac together can lead to serious adverse effects, including serotonin syndrome, which is a potentially life-threatening condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or loss of consciousness.
- Both medications can lower the seizure threshold, further increasing seizure risk when used together.
- 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, and modify treatment if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder 1.
Recommendations
- If you're currently taking Prozac and considering Contrave for weight management, consult your healthcare provider first to discuss alternatives.
- They might recommend completing a taper off Prozac before starting Contrave, switching to a different antidepressant with fewer interactions, or exploring alternative weight management medications.
- Never adjust these medications on your own, as proper medical supervision is essential when making changes to psychiatric medications.
Important Notes
- Bupropion is associated with a lower rate of sexual adverse events than fluoxetine or sertraline, whereas paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 1.
- SSRIs, such as fluoxetine, are associated with an increased risk for suicide attempts compared with placebo, and patients should be monitored for the emergence of agitation, irritability, or unusual changes in behavior, as these symptoms can indicate that the depression is getting worse 1.
From the Research
Interaction between Contrave and Prozac
The interaction between Contrave (bupropion and naltrexone) and Prozac (fluoxetine) is a significant concern due to the potential risk of serotonin syndrome.
- Bupropion, a component of Contrave, can increase the levels of selective serotonin reuptake inhibitors (SSRIs) like fluoxetine in the blood by inhibiting the cytochrome P450 2D6 pathway 2.
- A case study reported a patient who developed serotonin syndrome after taking a combination of bupropion and sertraline, another SSRI 2.
- Another study reported a case of delayed-onset serotonin syndrome in a patient who ingested a mixture of fluoxetine, cyproheptadine, trazodone, olanzapine, risperidone, and bupropion 3.
- However, there is no direct evidence of the interaction between Contrave and Prozac, and the available studies do not provide specific information on the safety of concomitant use of these medications.
Mechanism of Action
- Contrave is a combination therapy of bupropion and naltrexone, which works by stimulating central melanocortin pathways, resulting in increased energy expenditure and reduced appetite 4.
- Bupropion is a dopamine and norepinephrine reuptake antagonist, while naltrexone is an opioid antagonist 4.
- Fluoxetine, on the other hand, is an SSRI that increases the levels of serotonin in the brain.
Safety and Efficacy
- A systematic literature review found no increased risk of major adverse cardiovascular events (MACE) among users of Contrave, bupropion, or naltrexone compared to nonusers 5.
- Bupropion has been shown to be effective in the treatment of major depressive disorder, including as combination therapy with SSRIs 6.
- However, the safety and efficacy of concomitant use of Contrave and Prozac have not been specifically studied, and caution should be exercised when prescribing these medications together.