Brintellix by H. Lundbeck A/S and Takeda Pharmaceuticals America, Inc

The FDA has approved H. Lundbeck A/S and Takeda Pharmaceuticals America, Inc’s Brintellix (vortioxetine) for the treatment of major depressive disorder (MDD) in adults. The approval carries a boxed warning regarding an increased risk for suicidal thoughts and behaviors.¹ In 2010, clinical depression was the second-leading cause of global disability. It is estimated that 30 million Americans have been affected by MDD during their lifetime.²

Pharmacology and Pharmacokinetics

Brintellix’s mechanism of action is not fully understood, but it is believed to be related to its inhibition of the reuptake of serotonin (5-HT). It is an agonist at 5-HT1A receptors, a partial agonist at 5-HT1B receptors, and an antagonist at 5-HT3, 5-HT1D, and 5-HT7 receptors.^1,2

When administered once daily, Brintellix displays linear and doseproportional pharmacokinetics. The mean terminal half-life is approximately 66 hours, and steady-state plasma concentrations are usually achieved within 2 weeks of therapy.¹

Dosage and Administration

Treatment with Brintellix should be initiated as 10 mg orally once daily and increased to 20 mg daily when tolerated. In patients unable to tolerate higher doses, the dosage may be decreased to 5 mg daily. Treatment should be sustained for several months or longer. Treatment may be discontinued abruptly; however, decreasing the dosage to 10 mg daily for 1 week prior to cessation may minimize adverse reaction’s. Known CYP2D6 poor metabolizers should not use more than 10 mg daily. Brintellix may be taken without regard to food.¹

Clinical Trials

Brintellix was evaluated in 6 randomized, double-blind, placebocontrolled, fixed-dose studies of 6 to 8 weeks’ duration. Each study demonstrated that treatment with Brintellix was superior to treatment with placebo.

One study evaluated the role of Brintellix as maintenance treatment in adult inpatients and outpatients with MDD. All patients received Brintellix until week 12, at which point patients in remission were randomized to either continue Brintellix or placebo for 24 to 64 weeks. Patients using Brintellix experienced a statistically significantly longer time to recurrence of depressive episodes than those using placebo.^1,3

Contraindications, Warnings, and Precautions

Brintellix carries a boxed warning that antidepressant medications may increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults. Studies did not show an increased risk in adults older than 24 years and that risk may decrease in adults 65 years and older. All patients in whom antidepressant treatment is initiated should be monitored for worsening or emergence of suicidal thoughts or behaviors. Brintellix has not been studied for use in pediatric patients.

Brintellix is contraindicated in patients with a hypersensitivity to any of its components, patients using monoamine oxidase inhibitors (MAOIs) or who have used one with 14 days, or patients who are using linezolid or intravenous methylene blue. MAOIs should not be used within 21 days of discontinuation of Brintellix.

Patients using Brintellix should be monitored for serotonin syndrome, especially when Brintellix is administered concurrently with another serotonergic agent (eg, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s wort).

Patients using Brintellix may be at an increased risk for bleeding, especially when Brintellix is coadministered with nonsteroidal anti-inflammatory drugs, aspirin, or other drugs that affect coagulation. Treatment with antidepressants may activate mania or hypomania; patients should be screened for bipolar disorder. Hyponatremia may occur in association with the syndrome of inappropriate antidiuretic hormone secretion.

When Brintellix is used concurrently with a strong inhibitor of CYP2D6, the dose of Brintellix should be reduced by half. When Brintellix is coadministered with a strong CYP inducer, a higher dose of Brintellix may necessary. The maximum dose should not exceed 3× the original dose.

Brintellix is a Pregnancy Category C medication. It should not be used during breast-feeding.

The most common adverse reactions (≥5%) were nausea, constipation, and vomiting.¹

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.

References

• Brintellix [package insert]. Takeda Pharmaceuticals America, Inc, website. http://us.brintellix.com. Accessed April 2014.
• Brintellix (vortioxetine) for the treatment of major depressive disorder in adults is now available in US pharmacies. Takeda Pharmaceuticals America, Inc, website. www.takeda.com/news/2014/20140122_6162.html. Accessed April 2014.
• FDA approves new drug to treat major depressive disorder. FDA website. www.fda.gov/newsevents/newsroom/pressannouncements/ucm370416.htm. Accessed April 2014.