The Food and Drug Administration’s approval of vilazodone hydrochloride on Jan. 21 for the treatment of major depressive disorder in adults adds another drug to the already large group of antidepressants, though this one could offer a better side effect profile through a novel combined mechanism of action.
"Unlike other antidepressants, Viibryd [vilazodone hydrochloride] is the first and only drug that is both a potent selective serotonin reuptake inhibitor and serotonin 1A [5-HT1A] receptor partial agonist in one single molecule," said Clinical Data Inc.’s CEO Drew Fromkin during a call with analysts and investors on Jan. 24. Clinical Data’s PGxHealth division acquired the rights to develop Viibryd from Merck KGaA. The drug will be marketed under the trade name Viibryd.
"The net effect [of vilazodone] is that it’s boosting serotonin ... so it’s enhancing serotonin and, at the same time, boosting the serotonin signal for one of the receptors," Dr. Norman Sussman, a professor of psychiatry at the New York University’s Langone Medical Center, said in an interview.
Vilazodone will be available in 10-, 20- and 40-mg tablets, and the company expects the drug to be available in the second quarter of 2011. As with all other antidepressants, Viibryd will have a boxed warning on the label and a patient medication guide describing the increased risk of suicidal thinking and behavior in children, adolescents, and young adults aged 18-24 during initial treatment.
Based on the result of two 8-week placebo-controlled studies including 861 patients with MDD and a 52-week open-label study including 599 patients, the company believes that the drug is associated with decreased sexual dysfunction, which is something of an Achilles’ heel for selective serotonin reuptake inhibitors (SSRIs).
"The problem that you have with serotonin reuptake inhibitors ... is that there are certain quality of life side effects that are associated, like sexual dysfunction and weight gain, that have mitigated the benefits provided in the treatment of anxiety and depression," Dr. Sussman said.
"From my reading, it has most of the same side effects as the SSRIs. It causes nausea and diarrhea. It causes insomnia ... the only thing that didn’t come up in the 8-week studies was sexual dysfunction," he said. If the decreased effect on sexual dysfunction seen in the trials bears out, the drug could be a boon to clinicians and patients.
"As a clinician, that would be relevant to me. If it worked as well as the SSRIs – without any other side effects – but didn’t cause sexual dysfunction, that in itself would make it useful."
The first patients who will be treated with these drugs are likely to be those who have already been on trials of many other antidepressants without adequate relief of symptoms, he noted. "I think you might have another group of people who are doing well on SSRIs who are having sexual dysfunction. They may be candidates for it."
In part, the drug acts as a partial agonist at serotonergic 5HT1A receptors, which play a role in serotonergic transmission. "There seems to be a nuanced difference between this drug and the SSRIs and it’s probably because the 5-HT1A receptor may damp down whatever causes sexual dysfunction," Dr. Sussman said.
There is some history to support the efficacy of 5-HT1A receptor partial agonists. Buspirone also worked on the 5-HT1A receptor, said Dr. Sussman. The drug was approved in 1986 under the name BuSpar for the management of anxiety disorders or the short-term relief of the symptoms of anxiety.
Though never proven, "buspirone was one of the things that people claimed that some patients – not most – but some patients would be able to add to an SSRI to mitigate the sexual side effects," he said.
Dr. Sussman expressed concern, however, that the approval was based on two 8-week placebo-controlled studies including 861 patients with MDD. Those randomized to vilazodone were titrated up to 40 mg daily. It’s unclear how the drug would fare against other antidepressants currently available in terms of efficacy.
Based on the trial data, its maker believes that vilazodone also might minimize the weight gain that can accompany treatment with SSRIs. Dr. Sussman also cautioned that claims that weight gain is not associated with the drug might be premature. "They say that there was no weight gain in the 8-week studies but with the SSRIs in the 8-week studies, generally there was no weight gain either."
Dr. Sussman reported that he has no significant financial relationships.