Important Safety Information for TRINTELLIX (vortioxetine)
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a trend toward reduced risk with antidepressant use in patients aged 65 and older.
In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.
TRINTELLIX has not been evaluated for use in pediatric patients.
Hypersensitivity: Hypersensitivity to vortioxetine or any components of the TRINTELLIX formulation. Angioedema has been reported in patients treated with TRINTELLIX.
Monoamine Oxidase Inhibitors (MAOIs): Due to an increased risk of serotonin syndrome, do not use MAOIs intended to treat psychiatric disorders with TRINTELLIX or within 21 days of stopping treatment with TRINTELLIX. Do not use TRINTELLIX within 14 days of stopping an MAOI intended to treat psychiatric disorders. Do not start TRINTELLIX in a patient who is being treated with linezolid or intravenous methylene blue.
WARNINGS AND PRECAUTIONS
Clinical Worsening and Suicide Risk: All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality (anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania), especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants for MDD or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients daily.
Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with serotonergic antidepressants (SNRIs, SSRIs, and others), including TRINTELLIX, when used alone but more often when used concomitantly with other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Serotonin syndrome symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). If such symptoms occur, discontinue TRINTELLIX and any concomitant serotonergic agents, and initiate supportive symptomatic treatment. If concomitant use of TRINTELLIX is clinically warranted, patients should be made aware of and monitored for potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
Abnormal Bleeding: Treatment with serotonergic antidepressants (SSRIs, SNRIs, and others) may increase the risk of abnormal bleeding. Patients should be cautioned about the increased risk of bleeding when TRINTELLIX is coadministered with NSAIDs, aspirin, or other drugs that affect coagulation.
Activation of Mania/Hypomania: Activation of mania/hypomania can occur with antidepressant treatment. Prior to initiating treatment with an antidepressant, screen patients for bipolar disorder. As with all antidepressants, use TRINTELLIX cautiously in patients with a history or family history of bipolar disorder, mania, or hypomania.
Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs, including TRINTELLIX, may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
Hyponatremia: Hyponatremia has occurred as a result of serotonergic drugs and in many cases, appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Elderly patients and patients taking diuretics or who are otherwise volume-depleted can be at greater risk. More severe or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. Discontinue TRINTELLIX in patients with symptomatic hyponatremia and initiate appropriate medical intervention.
Adverse Reactions: The most commonly observed adverse reactions for TRINTELLIX in 6- to 8-week placebo-controlled studies (incidence ≥ 5% and at least twice the rate of placebo) were by dose (5 mg, 10 mg, 15 mg, 20 mg) vs placebo: nausea (21%, 26%, 32%, 32% vs 9%), constipation (3%, 5%, 6%, 6% vs 3%), and vomiting (3%, 5%, 6%, 6% vs 1%).
Drug Interactions: Concomitant administration of TRINTELLIX and strong CYP2D6 inhibitors or strong CYP inducers may require a dose adjustment of TRINTELLIX.
TRINTELLIX is indicated for the treatment of major depressive disorder in adults.
- 1. Conradi HJ, Ormel J, de Jonge P. Presence of individual (residual) symptoms during depressive episodes and period of remission: a 3-year prospective study. Psychol Med. 2011;41(6):1165-1174.
- 2. American Psychiatric Association. Depressive disorders. In: Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. Arlington, VA: American Psychiatric Association; 2013:155-188.
- 3. Trintellix (vortioxetine) prescribing information. Takeda Pharmaceuticals.
- 4. Alvarez E, Perez V, Dragheim M, et al. A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. Int J Neuropsychopharmacol. 2012;15(5):589-600.
- 5. Henigsberg N, Mahableshwarkar AR, Jacobsen P, et al. A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of Lu AA21004 in adults with major depressive disorder. J Clin Psychiatry. 2012;73(7):953-959.
- 6. Boulenger J-P, Loft H, Olsen CK. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder. Int Clin Psychopharmacol. 2014;29(3):138-149.
- 7. Mahableshwarkar AR, Jacobsen PL, Chen Y, et al. A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD. Psychopharmacology (Berl). 2015;232(12):2061-2070.
- 8. Data on file. Takeda Pharmaceuticals.
- 9. Jacobsen PL, Mahableshwarkar AR, Serenko M, et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with major depressive disorder. J Clin Psychiatry. 2015;76(5):575-582.
- 10. Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol. 2012;27(4):215-223.
- 11. Boulenger J-P, Loft H, Florea I. A randomized clinical study of Lu AA21004 in the prevention of relapse in patients with major depressive disorder. J Psychopharmacol. 2012;26(11):1408-1416.
- 12. Gelenberg AJ, Freeman MP, Markowitz JC, et al, for the Work Group on Major Depressive Disorder. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. Arlington, VA: American Psychiatric Publishing; 2010.
- 13. Werner F, Coveñas R. Classical neurotransmitters and neuropeptides involved in major depression in a multi-neurotransmitter system: a focus on antidepressant drugs. Curr Med Chem. 2013;20(38):4853-4858.
- 14. Baldwin DS, Chrones L, Florea I, et al. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies. J Psychopharmacol. 2016;30(3):242-252.