Trintellix, A Novel Antidepressant

Trintellix (vortioxetine) formerly named Brintellix is a multimodal antidepressant recently approved by the FDA for the treatment of major depressive disorder that has a number of pharmacologic effects marked by the following characteristics:

• Increases the release of serotonin, norepinephrine, dopamine, glutamate, acetylcholine, and histamine while reducing the release of GABA
• Blocks serotonin reuptake
• Binds to G protein-linked receptors
• Binds to ion channel-linked receptors
• Full agonist at the 5-HT_1A receptor provides an anxiolytic and antidepressant effect while diminishing sexual side effects
•  Partial agonist at the 5-HT_1B receptor associated with low weight gain
•  Antagonist at 5-HT_1D receptor associated with low weight gain and improved cognition
•  Antagonist at the 5-HT₃ receptor contributes to antidepressant effects and improves cognitive function by enhancing noradrenergic, acetylcholinergic, and glutamatergic activity and reduces nausea and vomiting caused by serotonin reuptake inhibition
• Antagonist at the 5-HT₇ receptor improves cognitive function, learning, and memory and contributes to antidepressant effects

These multimodal neurotransmitter effects contribute to usefulness in major depressive disorder, generalized anxiety disorder, cognitive symptoms associated with depression, and geriatric depression.

Clinical studies suggest that vortioxetine has a good safety and tolerability profile: Sexual dysfunction was low; vortioxetine had no significant effect on weight; and adverse events such as insomnia, fatigue, sedation, and somnolence were also low. Nausea, vomiting, and headache were the most common side effects.

Onset of action may be faster than most other antidepressants, with a clinical response in two weeks perhaps.

The recommended starting dose of Trintellix is 10 mg administered orally once daily without regard to meals. After one week dosage should then be increased to 20 mg daily, because higher doses demonstrated better treatment effects. A decrease down to 5 mg daily may be considered for patients who fail to tolerate higher doses. The long half-life (66-hours) of Trintellix allows the drug to be discontinued abruptly although prudence dictates tapering down to 10 mg daily for one week.