Is it safe to combine Trintellix (vortioxetine) with Rexulti (brexpiprazole)?

Safety of Combining Trintellix (Vortioxetine) with Rexulti (Brexpiprazole)

The combination of Trintellix (vortioxetine) and Rexulti (brexpiprazole) is generally considered safe with no significant drug-drug interactions reported between these two specific medications.

Pharmacological Considerations

• Vortioxetine (Trintellix) is a novel antidepressant with a unique mechanism of action, classified as a serotonin modulator that works as a serotonin transporter inhibitor and has activity at multiple serotonin receptors 1
• Brexpiprazole (Rexulti) is an atypical antipsychotic that acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors 2, 3
• Brexpiprazole has less intrinsic activity at D2 receptors compared to similar medications like aripiprazole, which may contribute to a lower propensity for activating adverse events 2

Safety Profile of the Combination

• Neither medication has been specifically identified in major drug interaction guidelines as having contraindications when used together 4
• Unlike some medication combinations that affect the same metabolic pathways significantly, vortioxetine and brexpiprazole do not appear to have clinically significant interactions that would require dose adjustments 1, 5
• Both medications are metabolized through the cytochrome P450 system, but there is no evidence of significant competitive inhibition that would lead to dangerous increases in blood levels of either medication 1, 2

Monitoring Recommendations

• Monitor for potential serotonergic effects when combining these medications, although the risk of serotonin syndrome is lower than with combinations of multiple strong serotonergic agents 6, 7
• Watch for common side effects of both medications, which may be additive:
  • Nausea (common with vortioxetine) 1
  • Weight gain (possible with brexpiprazole) 5
  • Akathisia (reported in 5.5-8.6% of patients taking brexpiprazole) 5

Clinical Considerations

• The combination may be particularly beneficial for patients with major depressive disorder who have had an inadequate response to antidepressant monotherapy, as brexpiprazole is FDA-approved as an adjunctive treatment for MDD 8, 3
• Brexpiprazole has demonstrated efficacy as an adjunctive therapy in MDD with a number needed to treat (NNT) of 12 for response 5
• When initiating this combination, it's advisable to start with established doses of one medication before adding the second agent to better monitor for any potential adverse effects 5

Potential Pitfalls and Precautions

• Although direct interaction between these two specific medications is not a major concern, be aware that adding other serotonergic medications to this combination could increase the risk of serotonin syndrome 6, 7
• Avoid adding MAOIs to this combination, as this would significantly increase the risk of serotonin syndrome 6
• Be cautious with additional medications that are substrates of CYP2D6 or CYP3A4, as both vortioxetine and brexpiprazole utilize these metabolic pathways 1, 2

In conclusion, the combination of Trintellix (vortioxetine) and Rexulti (brexpiprazole) appears to be safe based on their pharmacological profiles and the absence of specific contraindications in clinical guidelines. However, as with any medication combination, careful monitoring for potential side effects is recommended.