Dosing and uses of Trintellix, Brintellix [DSC] (vortioxetine)
Adult dosage forms and strengths
tablet, immediate-release
- 5mg
- 10mg
- 20mg
- NOTE: Former brand name Brintellix
Major Depressive Disorder
10 mg PO qDay initially; gradually increase to 20 mg/day as tolerated (higher doses demonstrated better treatment effects in clinical trials)
Not to exceed 20 mg/day
Dosage modifications
Consider decreasing dose to 5 mg/day if higher doses not tolerated
CYP2D6 poor metabolizers: Not to exceed 10 mg/day
Coadministration with CYP2D6 inhibitors: Decrease vortioxetine dose by 50%; increase dose to original level when CYP2D6 inhibitor discontinued
Coadministration with strong CYP inducers: Consider increasing the vortioxetine dose when strong CYP inducers is coadministered for >14 days; not to exceed 3 times original dose; decrease dose to original level within 14 days when the inducer is discontinued
Dosing Considerations
Former brand name Brintellix changed to Trintellix in June 2016 because of confusion with antiplatelet Brilinta (ticagrelor)
Acute episodes of major depression should be followed by several months or longer of sustained pharmacologic therapy; a maintenance study of vortioxetine demonstrated a decreased risk of recurrence of depressive episodes
Pediatric dosage forms and strengths
Safety and efficacy not established
Trintellix, Brintellix [DSC] (vortioxetine) adverse (side) effects
>10%
Nausea (21-32%)
1-10%
Diarrhea (7-10%)
Dizziness (6-9%)
Dry mouth (6-8%)
Constipation (3-6%)
Vomiting (3-6%)
Flatulence (1-3%)
Pruritus (1-3%)
Abnormal dreams (<1-3%)
Postmarketing Reports
Weight gain
Acute pancreatitis
Warnings
Black box warnings
Suicidality
- In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses; this increase was not seen in patients >24 years
- Slight decrease in suicidal thinking was seen in adults >65 years
- In children and young adults, risks must be weighed against the benefits of taking antidepressants
- Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments
- The patient’s family should communicate any abrupt changes in behavior to the healthcare provider
- Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy; this drug is not approved for use in pediatric patients
Contraindications
Hypersensitivity
Coadministration with MAOIs
- Coadministration of MAOIs with vortioxetine or within 3 weeks of discontinuing vortioxetine
- Initiating vortioxetine within 14 days of stopping an MAOI
- Starting vortioxetine in a patient who is being treated with linezolid or IV methylene blue is contraindicated because of an increased risk of serotonin syndrome
- If linezolid or IV methylene blue must be administered, discontinue vortioxetine immediately and monitor for CNS toxicity; monitor for symptoms of serotonin syndrome for 3 weeks or until 24 hours after the last dose of linezolid or methylene blue; may resume vortioxetine 24 hr after last dose of linezolid or methylene blue
Cautions
Clinical worsening of depression and suicide risk (see Black Box Warning)
May worsen mania symptoms or activate mania/hypomania in patients with bipolar disorder
Serotonin Syndrome reported with serotonergic antidepressants (SSRIs, SNRIs, and others), including with vortioxetine, both when taken alone, but especially when coadministered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort); if symptoms occur, discontinue therapy and initiate supportive treatment; if concomitant use with other serotonergic drugs is clinically warranted, patients should be made aware of potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases
Treatment with serotonergic antidepressants (SSRIs, SNRIs, and others) may increase risk of abnormal bleeding. patients should be cautioned about increased risk of bleeding when vortioxetine is coadministered with nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or other drugs that affect coagulation
Increases risk of hyponatremia and cognitive impairment especially in the elderly or volume depleted patients; hyponatremia can occur in association with the syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Angioedema reported with use
Seizures reported; use caution in patients with history of seizure disorders or conditions predisposing to seizures
Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy
Bone fractures reported with antidepressant treatment; consider possibility of fracture if antidepressant-treated patient presents with unexplained bone pain
Use not recommended in severe hepatic impairment
Discontinuation syndrome may occur with abrupt discontinuation; symptoms may include nausea, vomiting, diminished appetite, tremors, chills diarrhea, headaches, lightheadedness, fatigue, sleep disturbances (ie, insomnia, vivid dreams), and somnolence
Pregnancy and lactation
Pregnancy category: C
Use of SSRIs/SNRIs late in the third trimester has been associated with complications in newborns and may require prolonged hospitalization, respiratory support, and tube feeding
Persistent pulmonary hypertension of the newborn
Potential risk of persistent pulmonary hypertension of the newborn (PPHN) when SSRIs used during pregnancy
Recent studies have conflicting findings making it unclear whether use of SSRIs during pregnancy can cause PPHn
Lactation: Unknown if distributed in human breast milk; caution advised
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Trintellix, Brintellix [DSC] (vortioxetine)
Mechanism of action
The mechanism of the antidepressant effect is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS through inhibition of the reuptake of serotonin (5-HT)
It also has several other activities including 5-HT3 receptor antagonism and 5-HT1A receptor agonism; the contribution of these activities to the antidepressant effect has not been established
Absorption
Peak plasma concentration: 9, 18, and 33 ng/mL following doses of 5, 10, and 20 mg/day
Peak plasma time: 7-11 hr
Distribution
Protein bound: 98%
Vd: 2600 L (extensive extravascular distribution)
Metabolism
Extensively metabolized primarily through oxidation via CYP450 isozymes CYP2D6, CYP3A4/5, CYP2C19, CYP2C9, CYP2A6, CYP2C8 and CYP2B6 and subsequent glucuronic acid conjugation
CYP2D6 is the primary metabolic pathway
Metabolites: Carboxylic acid metabolite (inactive)
Elimination
Half-life: 66 hr
Excretion: 59% urine; 26% feces
Pharmacogenomics
Poor metabolizers of CYP2D6 have ~twice the vortioxetine plasma concentration of extensive metabolizers
Administration
Oral Administration
May take with or without food
Discontinuation
- Can be abruptly discontinued, although patients may experience transient adverse reactions (eg, headache, muscle tension) if dose is 15-20 mg/day
- To avoid these adverse reactions, decreased dose to 10 mg/day for 1 week before full
