From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Bupropion is the safest option to add to vilazodone due to its distinct mechanism of action that primarily targets dopamine and norepinephrine systems, reducing the risk of serotonin syndrome compared to other serotonergic antidepressants. When considering the addition of another antidepressant to vilazodone, it is crucial to weigh the potential benefits against the risks, particularly the risk of serotonin syndrome, which can be fatal. Vilazodone itself has selective serotonin reuptake inhibitor (SSRI) properties, making the combination with other serotonergic antidepressants like SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs) potentially hazardous 1.
Mechanism of Action and Safety Considerations
- Bupropion works primarily on dopamine and norepinephrine systems, with minimal effects on serotonin, making it a safer choice for combination therapy with vilazodone 1.
- Mirtazapine, with its unique mechanism of enhancing norepinephrine and serotonin neurotransmission by blocking alpha-2 presynaptic adrenoceptors, might also be considered in some cases, although its interaction profile with vilazodone should be carefully evaluated 1.
- The addition of any antidepressant to vilazodone should be done with caution, starting with low doses that are slowly titrated upward, and patients should be closely monitored for signs of serotonin syndrome, including confusion, rapid heart rate, dilated pupils, muscle rigidity, and high fever 2.
Clinical Evidence and Recommendations
- Clinical trials and reviews have shown vilazodone to be effective in treating major depressive disorder with a favorable side effect profile, including less sexual dysfunction and weight gain compared to other antidepressants 3, 4.
- However, the risk of serotonin syndrome with vilazodone, especially in combination with other serotonergic agents, necessitates careful consideration and monitoring 2.
- The decision to add another antidepressant to vilazodone should always be made by a psychiatrist who can weigh the potential benefits against the risks for the individual patient, considering factors such as the patient's medical history, current medications, and the potential for drug interactions 1, 5.
Conclusion on Safe Combination
Given the potential risks and the need for careful management, bupropion stands out as a preferable option for addition to vilazodone due to its mechanism of action and relatively safer profile regarding serotonin syndrome risk. However, each case must be evaluated individually, and the decision should be based on the most current and highest quality evidence available, prioritizing the patient's safety and well-being above all.