What are the possible interactions between vortioxetine (Brintellix) and modafinil (Provigil)?

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Last updated: May 30, 2025View editorial policy

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From the FDA Drug Label

The effects of other drugs on vortioxetine exposure are summarized in Figure 2. Figure 2 Impact of Other Drugs on Vortioxetine PK TRINTELLIX on Other Drugs The effects of vortioxetine on the exposures of other drugs are summarized in Figure 3. Figure 3 Impact of Vortioxetine on PK of Other Drugs In Vitro Vortioxetine and its metabolite(s) are unlikely to inhibit the following CYP enzymes and transporter based on in vitro data: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5, P-gp, BCRP, BSEP, MATE1, MATE2-K, OAT1, OAT3, OATP1B1, OATP1B3, OCT1 and OCT2 As such, no clinically relevant interactions with drugs metabolized/transported by these CYP enzymes or transporters would be expected.

The possible interactions between vortioxetine and modafinil are not directly addressed in the provided drug label.

  • No information is available on the interaction between vortioxetine and modafinil.
  • The label does not provide any data on the effects of modafinil on vortioxetine exposure or the effects of vortioxetine on modafinil exposure.
  • No conclusion can be drawn regarding the potential interaction between these two drugs based on the provided information 1.

From the Research

Based on current literature, there are no well-documented significant pharmacokinetic interactions between vortioxetine and modafinil, but caution is still warranted when combining these medications. Both medications can be used together, but patients should be monitored for potential serotonergic effects. Vortioxetine is an antidepressant that works through multiple serotonergic mechanisms, while modafinil is a wakefulness-promoting agent that has some weak dopaminergic and noradrenergic effects. The theoretical concern is that modafinil may slightly increase serotonin levels, which could potentially enhance vortioxetine's serotonergic effects, as suggested by studies on vortioxetine's pharmacology and clinical profile 2.

Key Considerations

  • Patients taking this combination should be aware of symptoms of serotonin syndrome, including agitation, confusion, rapid heart rate, dilated pupils, muscle rigidity, and hyperthermia.
  • No specific dosage adjustments are recommended when initiating this combination, but starting with standard doses of each medication and monitoring for side effects is prudent, as indicated by the pharmacokinetics of vortioxetine 3.
  • Both medications are metabolized by liver enzymes, primarily CYP3A4 and CYP2C19, but significant metabolic interactions have not been reported, as noted in a review of vortioxetine's drug interactions 4.
  • Patients should inform all healthcare providers about this combination and report any unusual symptoms promptly.

Monitoring and Precautions

  • Regular monitoring for serotonergic effects and other potential side effects is essential when combining vortioxetine and modafinil.
  • Healthcare providers should be aware of the potential risks and benefits of this combination and adjust treatment plans accordingly, considering the latest research on vortioxetine's effectiveness and safety 5, 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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