FDA Approves New Drug To Treat Depression

On September 3, just hours before the U.S. government went into partial shutdown, the Food and Drug Administration (FDA) approved Brintellix—which contains the active ingredient vortioxetine hydrobromide—to treat adults with major depressive disorder, which affects approximately 20 million Americans, according the Centers for Disease Control and Prevention.

“Major depressive disorder can be disabling and can keep a person from functioning normally,” said Mitchell Mathis, M.D., acting director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Since medications affect everyone differently, it is important to have a variety of treatment options available for patients who suffer from depression.”

Brintellix is comarketed by Takeda Pharmaceuticals and Lundbeck. It was granted agency approval without review of the drug’s efficacy and safety by a science advisory panel.

The FDA reviewed six global clinical trials that found Brintellix to be more effective than placebo in alleviating depression and preventing relapse in more than 4,700 participants with major depressive disorder aged 18 to 88. Throughout the studies, drug efficacy was evaluated by assessing changes in Hamilton Rating Scale for Depression (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS) total scores. The most common side effects reported included nausea, constipation, and vomiting.

Results from additional trials—not included in the FDA announcement—showed Brintellix to be statistically superior in efficacy and reduced side effects, such as sexual dysfunction, compared with other antidepressants. A comparative study was presented by Lundbeck in May at APA’s annual meeting in San Francisco. The FDA has declined to approve such superiority claims until they are confirmed by further research.

Product Will Carry FDA Warning

Similar to other antidepressants, Brintellix will carry a boxed warning for increased risk of suicidal thoughts and behavior in children, adolescents, and young adults aged 18 to 24 at treatment initiation. Studies showed that adults aged 24 to 64 did not appear to have an increased risk of suicidal thoughts and behavior, while adults aged 65 and older had a reduced risk. However, the FDA advised that, “Patients starting antidepressant therapy should be closely monitored for worsening of their depression and the emergence of suicidal thoughts and behavior.”

The antidepressant mechanism of Brintellix is not yet fully understood. It is an inhibitor of serotonin (5-HT) reuptake via blockade of the 5-HT transporter protein, which is thought to be one of Brintellix’s mechanisms of action. In addition, the drug is an agonist and a partial agonist for 5-HT1A and 5-HT1B receptors, respectively, which both stimulate serotonin release from presynaptic terminals. Other mechanisms have been speculated upon but have yet to be validated.

Future Trials Will Clarify Effectiveness

Matthew Rudorfer, M.D., associate director for treatment research at the National Institutes of Health and former chair of the FDA Psychopharmacological Drugs Advisory Committee, told Psychiatric News that further research testing the claims that Brintellix can bind to multiple serotonin receptor subtypes should be expected. He said that it must be determined if such claims “represent an incidental finding or a window into the underlying pathophysiology.”

Rudorfer emphasized that results from future clinical practice and effectiveness trials will ultimately determine how Brintellix will rank among existing antidepressants, in addition to Brintellix’s safety concerning drug-to-drug interactions.

Brintellix will be available for the U.S. market in the form of 5 mg, 10 mg, 15 mg, and 20 mg tablets. ■