Is it safe to combine Vraylar (cariprazine) with Trintellix (vortioxetine)?

Combining Vraylar (Cariprazine) and Trintellix (Vortioxetine) is Safe

Yes, it is safe to combine Vraylar (cariprazine) with Trintellix (vortioxetine), as neither medication has been identified as having contraindications when used together, and both have favorable drug interaction profiles. 1

Key Safety Considerations

No Direct Drug Interactions

• Neither cariprazine nor vortioxetine has specific contraindications when combined together 1
• Vortioxetine has minimal effect on cytochrome P450 (CYP) isoforms and does not significantly alter plasma concentrations of other medications metabolized by these enzymes 2
• Cariprazine is metabolized primarily by CYP3A4 and to a lesser extent by CYP2D6, with no documented interactions with vortioxetine 3

Serotonin Syndrome Risk is Low

• Monitor for potential serotonergic effects when combining these medications, though the risk of serotonin syndrome is lower than with combinations of multiple strong serotonergic agents 1
• Vortioxetine carries a relatively low risk for serotonin syndrome when used at therapeutic doses without other strong serotonergic agents 2
• The combination of a dopamine D3/D2 partial agonist (cariprazine) with a multimodal serotonergic antidepressant (vortioxetine) does not create additive serotonergic toxicity 1, 2

Clinical Context for This Combination

Complementary Mechanisms

• Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist with efficacy in schizophrenia, bipolar disorder, and as adjunctive therapy for major depressive disorder 4, 5
• Vortioxetine has multimodal serotonergic activity approved for major depressive disorder 2
• This combination may be particularly useful for treatment-resistant depression or when targeting both negative symptoms and mood 6, 5

Important Precautions

Avoid Adding Other Serotonergic Agents

• Do not add MAOIs to this combination, as this would significantly increase the risk of serotonin syndrome 1
• Be cautious when adding other serotonergic medications (SSRIs, SNRIs, triptans, tramadol) to this combination, as this could increase serotonin syndrome risk 1, 2

Monitor for Common Side Effects

• Cariprazine commonly causes insomnia, extrapyramidal symptoms, akathisia, sedation, nausea, dizziness, and constipation 3
• Vortioxetine is generally well-tolerated with minimal metabolic effects 2
• The combination does not appear to have clinically significant additive adverse effects on metabolic variables 3

Dosage Adjustments May Be Needed

• If strong CYP2D6 inhibitors are added to vortioxetine, dosage adjustments may be required 2
• Cariprazine doses of 1.5-12 mg/day have demonstrated efficacy, with no need for adjustment when combined with vortioxetine 3, 5