Combining Trintellix (Vortioxetine) with Rexulti (Brexpiprazole)
Yes, Trintellix (vortioxetine) can be safely combined with Rexulti (brexpiprazole), but caution should be exercised due to potential serotonergic effects, and the combination should be initiated at low doses with careful monitoring.
Pharmacological Considerations
Mechanism of Action
- Trintellix (vortioxetine): A multimodal antidepressant that acts as a serotonin transporter inhibitor with additional activity at multiple serotonin receptors (5-HT1A agonist, 5-HT1B partial agonist, 5-HT3, 5-HT1D, and 5-HT7 antagonist) 1, 2
- Rexulti (brexpiprazole): A dopamine D2 receptor partial agonist (atypical antipsychotic) used for schizophrenia and as an adjunctive treatment for major depressive disorder 3
Pharmacokinetics
- Vortioxetine has a long half-life of approximately 66 hours with steady-state plasma concentrations achieved within 2 weeks 4
- Vortioxetine is primarily metabolized by CYP450 enzymes, particularly CYP2D6 4
- Brexpiprazole is also metabolized by CYP2D6, which could potentially lead to increased plasma levels of both medications if used together 3
Safety Considerations
Serotonergic Effects
- When combining two or more serotonergic medications, there is an increased risk of serotonin syndrome 5
- Serotonin syndrome symptoms include:
- Mental status changes (confusion, agitation, anxiety)
- Neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity)
- Autonomic hyperactivity (hypertension, tachycardia, diaphoresis)
- In severe cases: fever, seizures, arrhythmias, unconsciousness 5
Drug Interactions
- Both medications may interact with CYP2D6 inhibitors, potentially increasing plasma concentrations 4
- Avoid combining with MAOIs due to high risk of serotonin syndrome 5
- Monitor for potential QT prolongation, especially if other QT-prolonging medications are used 5
Recommendations for Combined Use
Initiation Strategy
- Start with low doses of both medications when using them in combination
- Titrate slowly - increase doses at 1-2 week intervals for shorter half-life medications 5
- Monitor closely for symptoms of serotonin syndrome, especially in the first 24-48 hours after dosage changes 5
Monitoring Parameters
- Mental status changes (confusion, agitation, anxiety)
- Neuromuscular symptoms (tremors, hyperreflexia)
- Vital signs (blood pressure, heart rate, temperature)
- Sleep quality and patterns
- Therapeutic response
- Sexual function (as both medications may cause sexual dysfunction) 5
Clinical Considerations
Benefits of Combination
- The combination may be beneficial for patients with depression who have had an inadequate response to antidepressant monotherapy
- Brexpiprazole has shown efficacy as an adjunctive treatment in MDD with an NNT of 12 (95% CI 8-26) 3
- Vortioxetine has unique procognitive properties that may benefit patients with cognitive symptoms of depression 2
Potential Adverse Effects
- Common side effects:
- Nausea (most common with vortioxetine)
- Akathisia (common with brexpiprazole - 8.6% in MDD trials) 3
- Weight gain (more common with brexpiprazole)
- Somnolence/sedation
- Sexual dysfunction
Practical Approach to Combination Therapy
- Establish baseline: Document current symptoms, side effects, and response to current therapy
- Add second agent at low dose: If patient is already on one medication, add the second at a low dose
- Gradual titration: Increase dose slowly based on response and tolerability
- Regular monitoring: Assess for both therapeutic response and adverse effects
- Dose adjustment: Modify doses based on individual response and side effect profile
Cautions and Contraindications
- Avoid in patients with a history of serotonin syndrome
- Use with caution in patients with seizure disorders
- Monitor closely in patients with cardiovascular disease
- Exercise caution in patients taking other serotonergic medications
By following these guidelines, the combination of Trintellix and Rexulti can be safely administered with appropriate monitoring and dose adjustments.