SSRI, SNRI – It’s the SAME. Just say “SRI”

by | Apr 18, 2023 | Blog posts

Doctor: I’m giving you Cymbalta (duloxetine).
Patient: I got manic and suicidal on SSRIs. Is it an SSRI?
Doctor: Don’t worry. It’s a SNRI.
Patient: Oh.

This 19 year old male had experienced worsened suicidality twice previously with fluoxetine and sertraline. He knew “SSRIs” were bad for him but he had never heard of “SNRIs”.

It’s not just a minor issue to use a false phrase like “SSRIs”. These agents are not “selective” and thus they should simply be called “SRIs”, or serotonin reuptake blockers. If we did so, we would realize that there is no difference between all these agents, including duloxetine and fluoxetine. In fact, the former waderived from the latter by the same company, Eli Lilly, and BOTH agents have both serotonin and norepinephrine reuptake blockade. They are BOTH SNRIs if you want to use that phrase, for what it’s worth. But more importantly all SRIs have other monoamine effects, except citalopram. All except that agent also have dopamine or norepinephrine reuptake blockade. They are not selective for serotonin at all.

Let’s review where this all started.

Thirty years ago, some smart marketing folks at Eli Lilly came up with the phrase “selective” to add before “serotonin reuptake” for a new medication, fluxoetine (Prozac), which was the first such agent to enter the US market. Prior medications, the tricyclic antidepressants, were norepinephrine and serotonin reuptake inhibitors (mostly), and thus the claim was that the new drug which was “only” a serotonin reuptake blocker was better because it was “selective” for serotonin over norepinephrine. In fact, this selectivity had some benefit for side effects, though not for efficacy, where the TCAs would prove to be more effective. The term “selective” was false to begin with since fluoxetine did have norepinephrine reuptake blocade, it just had less of the latter than TCAs. So it was a matter of more or less, not all or none.

After fluoxetine, sertraline came out, and it had strong dopamine reuptake blockade, which everyone ignored. It got called a SSRI. Then venlafaxine came out, and because it wanted to distinguish itself from its competitors, it called itself a “SNRI”, which is exactly the same mechanism of tricyclic antidepressants. The makers of venlafaxine did not point out that fluoxetine had about the same amount of norepinephrine blockade as venlafaxine.

Why does a profession parrot a phrase created three decades ago for pharmaceutical marketing? Stop saying “SSRI” psychiatrists and clinicians. A simple solution for a false phrase. As the example above shows, in the hands of simplistically-thinking clinicians, such false phrases can harm. George Orwell wouldn’t be happy.