Vortioxetine (Trintellix)

Contents

Vortioxetine (Trintellix) is an antidepressant with many actions (also termed a multimodal antidepressant). In addition to being a serotonin reuptake inhibitor, Vortioxetine has numerous effects at other receptor sites which work together in complex and poorly understood ways to produce an antidepressant effect.

Clinical Information

ROUTE OF ADMINISTRATION: Oral

HALF-LIFE: 66 hours

TIME TO STEADY STATE: 2 weeks

PEAK IN PLASMA: 7-11 hours

PLASMA PROTEIN BOUND: 98%

METABOLISM: Hepatic; Phase I+II; CYP2D6; Inactive metabolites

HEPATIC IMPAIRMENT (HI): No dose adjustment for mild/moderate HI

RENAL IMPAIRMENT (RI): No dose adjustment needed

FOOD or FAST (PO)? Either

STARTING DOSE:

~10mg PO daily (18-65 years old)

~5mg PO daily (>65 years old)

TARGET DOSING RANGE: 5-20mg / day

BEST TIME TO DOSE: Morning after a meal or night

HOW TO DOSE:
>>Start 5mg-10mg per day and increase dose by 5mg after two (2) weeks based on response and tolerability.

>>Max dose typically 20mg/day 

PREGNANCY: Not enough information.

BREASTFEEDING: Not enough information. 

Side Effects

Nausea (Dose dependent; usually first few weeks), vomiting, constipation

Drug Interactions

  • Avoid with MAOIs
  • If switching from or to an MAOI, washout is 2 weeks
  • Not an inducer/inhibitor of CYP450
  • If given with 2D6 Inhibitors (paroxetine, fluoxetine), AUC is doubled
  • May reduce effects of triptans used for migraines (via 5HT1D antagonism)

FDA Indications

  1. Major depressive disorder 

Mechanism(s) of Action

  • SERT Inhibition (serotonin reuptake inhibition)
  • 5HT1A Full Agonist
  • 5HT1B Partial Agonist
  • 5HT1D Antagonist
  • 5HT3 Antagonist
  • 5HT7 Antagonist

Additional Information

  • Some evidence that vortioxetine improves cognitive symptoms of depression
  • Minimal to no sexual dysfunction at dosages of 5mg-10mg
  • Dosages of 20mg/day showed similar sexual side effects as duloxetine 60mg/day
  • Minimal to no withdrawal syndrome (due to long half-life)
  • Minimal to no effects on body weight
  • No clinically meaningful QTc changes after 14 days of 40mg/day 

References

  1. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  2. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  3. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.