Two Pill Bottles With Text - Trintellix With Pristiq


There is an interaction to be concerned about between Trintellix (vortioxetine) and Pristiq (desvenlafaxine).

Although they aren't in the same class of medication, both cause increases in the neurotransmitter serotonin, which can increase the risk of a rare but serious disorder known as serotonin syndrome.[1]

They generally aren't prescribed together due to the similarity in how they work and their side effect profile.

Serotonin Syndrome

Taking Trintillix with Pristiq puts you at risk for additive adverse effects, with serotonin syndrome being the most concerning.

Serotonin syndrome is rare, but serious if it occurs. The biggest risk factor for serotonin syndrome is combining drugs that can increase concentrations of the neurotransmitter in the brain (like Pristiq and Trintellix do).

Serotonin syndrome is characterized by a variety of symptoms, including:[2]

  • Increased body temperature
  • Increased blood pressure
  • Sweating
  • Delerium
  • Confusion
  • Muscle spasms
  • Coma

If any of these symptoms occur while taking a serotonergic drug, it should be stopped and immediate medical attention should be sought.

There haven't been any studies evaluating the risk of serotonin syndrome with Trintellix and Pristiq specifically, but it is generally accepted that taking more than one drug that increases serotonin puts you more at risk.

The prescribing information for both drugs warns about the use of more than one serotonergic drug.

The following is from the prescribing information for Trintellix:[3]

"The development of a potentially life-threatening serotonin syndrome has been reported with serotonergic antidepressants including TRINTELLIX, when used alone but more often when used concomitantly with other serotonergic drugs..."
Trintellix Prescribing Information

How They Work

As mentioned, Trintellix and Pristiq but work similarly, but there are some key differences.

Pristiq is classified as an SNRI, or serotonin-norepinephrine reuptake inhibitor. Inhibiting the reuptake of these neurotransmitters results in increased levels of both in the brain.[4]

Trintellix is unique in its mechanism of action and does not belong to any of class of medication, including SSRIs and SNRIs.

How exactly it works isn't completely understood but it is thought to not only inhibit the reuptake of serotonin but also acts directly on serotonin receptors. In fact, studies show it agonizes (i.e. stimulates) certain serotonin receptors but antagonize (i.e. blocks) others.[5]

Final Words

Although these drugs aren't often prescribed together, there certainly could be situations where they represent the best therapy for a particular medical situation.

Be sure to talk to your doctor regarding taking both of these together and your concerns if you have any. Also be sure to know of the potential symptoms of serotonin syndrome, just in case.


Taking Pristiq and Trintellix together increases the risk of serotonin syndrome. They aren't often prescribed together but combined use isn't contraindicated.

  1. ^ Elsevier ClinicalKey: Interactions. ClinicalKey
  2. ^ Serotonin Syndrome. PubMed
  3. ^ Trintellix Prescribing Information. Takeda
  4. ^ Elsevier ClinicalKey: Pristiq Monograph.. ClinicalKey
  5. ^ Elsevier ClinicalKey: Trintellix Monograph. ClinicalKey