Drug evaluation: Vilazodone--a combined SSRI and 5-HT1A partial agonist for the treatment of depression

Vilazodone is a combined selective serotonin reuptake inhibitor (SSRI) and a 5-HT(1A) receptor partial agonist that is being developed by Clinical Data Inc for the treatment of depression. In preclinical studies, vilazodone compared favorably to other antidepressants such as paroxetine and fluoxetine. Orally administered vilazodone inhibited ultrasonic vocalization in the rat after electrical foot shock (a model of anxiolytic activity). Yet, in the forced swimming test model of depression in rats, vilazodone administered intraperitoneally was active at 1 mg/kg but not at 3 or 10 mg/kg. During clinical trials, vilazodone completely abolished REM sleep for 8 h and demonstrated antidepressant efficacy that was equal to that of current antidepressant therapeutics. The author concludes that the success of vilazodone as an effective antidepressant agent will depend on whether the drug can produce a more rapid antidepressant effect than other SSRI agents, or if specific genetic markers of patients can be associated with clinical efficacy.