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FDA Publishes Article Critical of Vilazodone Data
Subject:
ANTIDEPRESSANTS
Short Description:
FDA Publishes Article Critical of Vilazodone Data
Background:
It has been over a year now since the approval of vilazodone (Viibryd). As you may recall from our review of the drug in TCPR April 2011, vilazodone is an SSRI with partial agonism at the 5HT1A receptor. This “dual mechanism” of action means that one can think of the drug as though it combines an SSRI with buspirone (which also is a partial 5HT1A agonist). We predicted that vilazodone would be pushed as a “low sexual side effect” alternative to standard SSRIs. While we do not allow drug reps into our offices at Carlat Publishing, our moles in the field have told us that drug reps have indeed been aggressively brandishing data regarding Viibryd’s sexual side effects.
Recently, the FDA, in what may be an unprecedented move, published an article essentially warning practitioners not to believe the hype about the drug. The article, published in the Journal of Clinical Psychiatry, summarizes various aspects of the FDA review of the vilazodone data submitted by Forest, the manufacturer. In their review, the FDA dispels two myths, and offers up one point of caution about the drug.
Myth #1: Vilazodone works faster than other antidepressants. This was based on one of Forest’s trials that showed that vilazodone separated from placebo by week one. The FDA points out two problems. First, this data was from Trial 04, which was only one of two large trials submitted as part of the new drug application. In the other trial, Trial 07, vilazodone did not separate from placebo until week four. Second, neither trial compared vilazodone with an already approved SSRI, meaning that no statements can be made about the new drug working faster than existing antidepressants.
Myth #2: Vilazodone causes less sexual dysfunction than other antidepressants. The major problem is that vilazodone was not compared to an antidepressant known to cause sexual dysfunction. Beyond that, the FDA points out that even the results comparing vilazodone to placebo were inconsistent, “showing worsening on some items and improvement on others.”
And finally, a warning: vilazodone is a dosing challenge. The 20 mg dose may not be effective, as it was not adequately tested. This is why the manufacturer states that 40 mg is the recommended dose. The problem is that in order to prevent common vilazodone GI side effects of nausea and diarrhea, we are supposed to titrate gradually by starting at 10 mg for a week, then 20 mg for a week, then ending at 40 mg. Go above 40 mg, and the drug is “poorly tolerated,” according to the FDA. What happens if a patient can’t even tolerate the bump up to 40 mg? You might be tempted to go back to 20 mg for a while, but the 20 mg dose is not clearly effective. The entire process will mean lost time for some patients who are suffering (Laughren TP et al, J Clin Psychiatry72(9):1166–1173).
TCPR's Take:
The bottom line is that vilazodone has no proven advantages over other SSRIs, and it has special dosing issues that present challenges that are absent in other SSRIs. For these reasons, we recommend that you relegate vilazodone to second-line status in your quiver of remedies.
General PsychiatryANTIDEPRESSANTS
Short Description:
FDA Publishes Article Critical of Vilazodone Data
Background:
It has been over a year now since the approval of vilazodone (Viibryd). As you may recall from our review of the drug in TCPR April 2011, vilazodone is an SSRI with partial agonism at the 5HT1A receptor. This “dual mechanism” of action means that one can think of the drug as though it combines an SSRI with buspirone (which also is a partial 5HT1A agonist). We predicted that vilazodone would be pushed as a “low sexual side effect” alternative to standard SSRIs. While we do not allow drug reps into our offices at Carlat Publishing, our moles in the field have told us that drug reps have indeed been aggressively brandishing data regarding Viibryd’s sexual side effects.
Recently, the FDA, in what may be an unprecedented move, published an article essentially warning practitioners not to believe the hype about the drug. The article, published in the Journal of Clinical Psychiatry, summarizes various aspects of the FDA review of the vilazodone data submitted by Forest, the manufacturer. In their review, the FDA dispels two myths, and offers up one point of caution about the drug.
Myth #1: Vilazodone works faster than other antidepressants. This was based on one of Forest’s trials that showed that vilazodone separated from placebo by week one. The FDA points out two problems. First, this data was from Trial 04, which was only one of two large trials submitted as part of the new drug application. In the other trial, Trial 07, vilazodone did not separate from placebo until week four. Second, neither trial compared vilazodone with an already approved SSRI, meaning that no statements can be made about the new drug working faster than existing antidepressants.
Myth #2: Vilazodone causes less sexual dysfunction than other antidepressants. The major problem is that vilazodone was not compared to an antidepressant known to cause sexual dysfunction. Beyond that, the FDA points out that even the results comparing vilazodone to placebo were inconsistent, “showing worsening on some items and improvement on others.”
And finally, a warning: vilazodone is a dosing challenge. The 20 mg dose may not be effective, as it was not adequately tested. This is why the manufacturer states that 40 mg is the recommended dose. The problem is that in order to prevent common vilazodone GI side effects of nausea and diarrhea, we are supposed to titrate gradually by starting at 10 mg for a week, then 20 mg for a week, then ending at 40 mg. Go above 40 mg, and the drug is “poorly tolerated,” according to the FDA. What happens if a patient can’t even tolerate the bump up to 40 mg? You might be tempted to go back to 20 mg for a while, but the 20 mg dose is not clearly effective. The entire process will mean lost time for some patients who are suffering (Laughren TP et al, J Clin Psychiatry72(9):1166–1173).
TCPR's Take:
The bottom line is that vilazodone has no proven advantages over other SSRIs, and it has special dosing issues that present challenges that are absent in other SSRIs. For these reasons, we recommend that you relegate vilazodone to second-line status in your quiver of remedies.
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