Vilazodone is a perfectly fine antidepressant, but it is expensive and not particularly more effective than others, so for cost reasons we would not go to it first; it is worth a try for someone who has a hard time tolerating other medications. Its mechanism, an SSRI plus 5-HT1 partial agonism, is for us a reason not to use it, since we like using buspirone on top of SSRIs. It is marketed as having slightly lower sexual side effects.
When we reach for it
A perfectly fine medication, but expensive and not particularly more effective than others, the traditional SSRIs included (though we have not used it a lot). For cost reasons we would not go to it first, but someone who has a hard time tolerating medications may tolerate it better than the others, so it is worth a try.
“This is expensive. It's not particularly more effective than others. If you're having someone who has a hard time tolerating medications, they might be able to tolerate it better than the other ones. It's worth a try”
1:01:49Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 Also said in 1 more episode
“They're perfectly fine medications. I don't find them particularly superior to the SSRIs, the traditional ones, I mean. But, you know, I haven't used them very much. So unfortunately, I can't comment. For cost reasons, I wouldn't go to them first”
40:40Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 Its mechanism is an SSRI plus 5-HT1 partial agonism. We think that is actually a reason not to use it, because we like using buspirone on top of SSRIs.
“the mechanism of action is an SSRI plus 5-HT1 partial agonism. So I think that's actually a reason not to use it because I do like using Buspirone on top of SSRIs”
29:02Anxiety Medications Tier List: The Best and Worst Treatments for GADJul 2026
Side effects and safety
Vilazodone and vortioxetine are the two medications we have seen marketed as having slightly lower sexual side effects.
“I have seen that Vilazodone and Vortioxetine are the two meds that are marketed as slightly lower sexual side effects”
36:28Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025
From these episodes
- Anxiety Medications Tier List: The Best and Worst Treatments for GADJul 2026 · 1 point
- Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDDMay 2026 · 1 point
- Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 2025 · 1 point
- Treating Depression: Practical Tips & Pearls for Anti-Depressant MedicationsJan 2025 · 1 point
Every point above is something said on the Psychofarm podcast, with the words as spoken and a link to the moment in the episode. It is education, not medical advice, and an episode reflects what we thought when we recorded it.