Viibryd has gone generic, but is it worth prescribing? We review all there is to know about vilazodone in this update from our #1 most read article of 2023.

Publication Date: 04/01/2024

Duration: 12 minutes, 47 seconds

Transcript: 

KELLIE NEWSOME: Today, we look back on a decade of research on vilazodone as this antidepressant goes generic.

CHRIS AIKEN: Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report.

KELLIE NEWSOME:And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue. Today we have the #1 most read article from 2023: Viibryd Goes Generic, But Is It Worth Prescribing? This one’s by Dr. Aiken, and he has no conflicts to disclose. You can read all of the top 15 articles free online through the link in the show notes or just Google “Top 15 Carlat Psychiatry Articles of 2023.” 

CHRIS AIKEN: After 11 years of market exclusivity, vilazodone (Viibryd) lost its patent in June of 2022. The price of this “multimodal” antidepressant has fallen to $40 a month. More patients can afford to take it, but whether we should prescribe more vilazodone is less clear.

KELLIE NEWSOME: Here’s how it works. In the brain, vilazodone acts like a combination of an SSRI and buspirone. Like an SSRI, it is a potent serotonin reuptake inhibitor, and like buspirone, it is a 5-HT1A serotonin agonist. Vilazodone’s manufacturer hoped this dual mechanism would lead to faster onset, more anxiolytic effects, and fewer sexual side effects. At first, those hopes seemed to pan out, but today they only hold up if the data are cherry-picked. Let’s look at those hopes one by one, starting with whether it has a faster onset.

CHRIS AIKEN: Vilazodone’s clinical efficacy rests on four large, short-term randomized controlled trials in major depression. In the first trial, it separated from placebo at one week, and in another it separated at two weeks. However, there was no early response in the remaining two trials, and most antidepressants have some evidence of early efficacy within the first two weeks, so even a generous interpretation here does not suggest that anything special is going on (Chauhan M et al, Neuropsychiatr Dis Treat 2022;18:1175–1193). So it’s not faster, but is it more effective?

None of the vilazodone trials suggest greater potency than other antidepressants. Its antidepressant effects were similar to those of citalopram 40 mg/day in a large head-to-head trial of 1,133 patients. That study also compared two fixed doses of vilazodone (20 mg and 40 mg) and found no evidence of greater benefits at the higher dose (Mathews M et al, Int Clin Psychopharmacol 2015;30(2):67–74). 

Overall, vilazodone’s efficacy is similar to that of other modern-day antidepressants, which is not particularly high. The number of patients needed to treat (NNT) to achieve a response with vilazodone that wouldn’t have been seen with a placebo is 8, compared to 4–16 for other antidepressants—with a lower NNT indicating greater efficacy (Citrome L, J Affect Disord 2016;196:225–233). Whether vilazodone can reliably bring patients to full remission is debatable. A meta-analysis suggests that 10% of patients achieve remission on vilazodone, but the only large trial that reported remission rates found it was no better than placebo (Khan A et al, J Clin Psychiatry 2011;72(4):441–447). 

KELLIE NEWSOME: Vilazodone is no more effective than other meds, but does its unique mechanism give it a niche in treatment resistant depression? Probably not. Vilazodone has never been tested in treatment-resistant depression, but two “switch” studies in patients who failed to recover after a trial of an SSRI or SNRI cast doubt about its ability to work when other antidepressants have not. Its long-term data are also uninspiring. Vilazodone failed to prevent depression in a large study that randomized patients who responded to the drug to either placebo or continuation. That is telling, since these “enriched” study designs usually favor the antidepressant (Chauhan et al, 2022).

Let’s pause for a preview of the CME quiz for this episode. Start earning CME for this podcast through the link in the show notes.

1. What is the main limitation of vilazodone in depression?

A. Poor tolerability

B. Lack of preventative data

C. Drug interactions

D. Withdrawal problems

CHRIS AIKEN: One of the most common myths we hear about new drugs is that they have an edge in anxiety. Anxiety is a non-specific symptom - a synonym for distress – that tends to improve as the underlying disorder improves. So if you run an anxiety scale as part of a treatment study in schizophrenia, mania, or depression you’re likely to see it go down, but that doesn’t mean that the antipsychotic, mood stabilizer, or antidepressant is an anxiolytic. So what about vilazodone, does it have any niche in anxiety?

With its resemblance to SSRIs and buspirone, vilazodone might seem well suited for anxiety disorders. However, its lack of FDA approval in anxiety disorders, despite industry-supported trials in generalized and social anxiety, raises doubts. Vilazodone did work in three large randomized controlled trials of generalized anxiety disorder (20–40 mg/day, mean 31 mg/day), but the effect size was small and its tolerability was poor in this population, particularly with nausea and diarrhea (Zareifopoulos N and Dylja I, Asian J Psychiatr 2017;26:115–122). An industry-sponsored social anxiety trial was positive, but the study was small and the dropout rate high. A larger follow-up study in social anxiety disorder was abandoned midstream.

KELLIE NEWSOME: The story brightens when we turn to anxious depression, but not enough to endorse vilazodone as a first-line option. Michael Thase and colleagues reanalyzed two large vilazodone trials to see if its effects differed in those with anxious vs nonanxious depression (the majority, 82%, fell into the anxious category). Vilazodone improved both anxiety and depression in the anxious group but did not work at all in those with nonanxious depression (Thase ME et al, Int Clin Psychopharmacol 2014;29(6):351–356). That almost sounds like an endorsement of vilazodone in anxious depression, except for this: A large trial found that citalopram was a more effective anxiolytic in depressed patients than vilazodone.

CHRIS AIKEN: Now let’s talk about tolerability, and there’s one area where vilazodone has an edge – sex. When vilazodone was first launched, the initial data suggested the drug lacked sexual side effects. Later, we learned that most of the patients in those trials had nothing to lose, as their sex drive was already close to zero when they started vilazodone. While vilazodone did not lower their already absent libido, it did cause sexual dysfunction in those who entered the study with their sex drives intact (at a rate of 8% vs 1% on placebo). Later head-to-head comparisons with sertraline and paroxetine suggested that vilazodone carries a lower risk of sexual dysfunction than the SSRIs, consistent with the partially supported idea that buspirone treats SSRI-induced sexual dysfunction (Chauhan et al, 2022).

KELLIE NEWSOME: Overall, vilazodone’s tolerability problems are similar to those of the SSRIs, with transient nausea, diarrhea, dizziness, and more lasting sexual dysfunction and insomnia. There is no reason to think that vilazodone is free of more serious SSRI side effects like hyponatremia, osteopenia, suicidality, and withdrawal problems, but research into these areas is scant.

CHRIS AIKEN: Here’s how to prescribe it. Vilazodone dosing is relatively straightforward, with a few obstacles that are described in the table. For example, it needs to be taken with food—up to half the dose goes unabsorbed in a fasted state. On the other hand, potent CYP3A4 inhibitors, such as grapefruit juice, can raise vilazodone levels about two-fold. 

KELLIE NEWSOME: The bottmline. Consider vilazondone in patients who respond to an SSRI but need an antidepressant with a lower risk of sexual side effects, and who do not respond to bupropion and vortioxetine (where sexual side effects are closer to zero). Otherwise, there are several reasons to avoid this antidepressant first line; tolerability, food interactions, and questionable benefits when it comes to preventing depression or treating comorbid anxiety disorders.

KELLIE NEWSOME: We have a new program - Carlat Psychiatry News - where we'll bring you monthly updates of all things psychiatric. Check out our April edition on the Carlat Webiste - search for webinars. Check out the online article for a Carlat table on how to use vilazodone.

__________

The Carlat CME Institute is accredited by the ACCME to provide continuing medical education for physicians. Carlat CME Institute maintains responsibility for this program and its content. Carlat CME Institute designates this enduring material educational activity for a maximum of one quarter (.25) AMA PRA Category 1 Credits^TM. Physicians or psychologists should claim credit commensurate only with the extent of their participation in the activity.