We grade imipramine, and the tricyclics with it, A minus for generalized anxiety: the last step of the traditional algorithm after SSRIs, an SNRI, and gabapentin and pregabalin. It holds that spot only because it was the most researched, so in practice use whichever tricyclic is tolerated, such as nortriptyline.
When we reach for it
The traditional algorithm goes SSRIs, then an SNRI, then gabapentin and pregabalin, and then a tricyclic.
“The traditional algorithm goes SSRI SSRI and SNR. SNRI, and then you try your gabapentin and Lyrica, and then you try your TCA”
1:00:20Anxiety Medications Tier List: The Best and Worst Treatments for GADJul 2026
Choosing a tricyclic
It is the tricyclic people name for anxiety only because it was the one researched most back in the day. You can use it, but really it is whichever tricyclic is tolerated, and we believe nortriptyline is classically one of the better tolerated.
“What's interesting is that that's just because that was the one that was researched the most back in the day. So, you know, you can go for imipramine. But really, it's whatever tricyclic is tolerated. I believe nortriptyline is usually... one of the classically better tolerated ones”
37:54Psychiatrist'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
- Psychiatrist's Guide to Anxiety Medications: First Line to Last ResortJun 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.