Vortioxetine [1-[2-(2,4-Dimethylphenyl-sulfanyl)-phenyl]-piperazine] is an orally administered small molecule developed as once-daily treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). As a drug, Vortioxetine is a bis-aryl-sulphanyl amine compound that combines serotonin (5-HT) reuptake inhibition with other characteristics, including receptor activity modulation.
|Vortioxetine: 2D and 3D Structure|
Vortioxetine binds to the human serotonin (5-HT) transporter (SERT) with high affinity (Ki = 1.6 nM) and is a potent inhibitor of serotonin reuptake (IC50 = 5.4 nM), whereas its affinity for transporters of noradrenaline (Ki = 113 nM) and dopamine (Ki greater than 1000 nM) is much lower or negligible. The drug also has a broad receptor-binding profile, binding to the 5-HT1A receptor (Ki = 15 nM) where it acts as an agonist, the 5-HT1B receptor (Ki = 33 nM) where it acts as a partial agonist, and the 5-HT1D, 5-HT3 and 5-HT7 receptors (Ki = 54, 3.7 and 19 nM, respectively) where it displays antagonistic properties [1, 2].
In September 2013, Vortioxetine was approved as Brintellix for the once-daily treatment of adults with MDD in the USA and one month later, EMA approved it as it first in line treatment for Europeans with MDD. It is marketed as Trintellix in Canada.
Vortioxetine was discovered by scientists at Lundbeck, where it was known as Lu AA21004. Takeda and Lundbeck entered into a strategic alliance to co-develop and co-commercialise vortioxetine and tedatioxetine in Japan and the USA in September 2007. The two companies will jointly complete product development, which will be funded primarily by Takeda, and the companies will share revenue generated in the USA and Japan.
Vortioxetine is administered orally at a starting dosage of 10 mg/day, with the dosage increased to 20 mg/day, as tolerated; 5 mg/ day may be considered if higher dosages are not tolerated. Dosages greater than 20 mg/day have not been assessed for efficacy or safety in controlled trials.
Serious adverse events occurred in some patients, with those considered to be vortioxetine related including left hemispheric ischaemic stroke, tachycardia (paroxysmal and supraventricular), depression and major depression.
Moreover, some patients who abruptly discontinue vortioxetine 15 or 20 mg/day may experience symptoms such as mood swings, sudden outburst of anger, headache, dizziness, muscle tension or runny nose within the first week post discontinuation.
1. Gibb, A.; et. al. Vortioxetine: first global approval. Drugs 2014, 74(1), 135-145.
2. Bang-Andersen, B.; et. al. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem 2011, 54(9), 3206-3221.
3. Bang-Andersen, B.; et. al. 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl] piperazine as a compound with combined serotonin reuptake, 5-ht3 and 5-ht1a activity for the treatment of cognitive impairment WO2007144005A1