[https://astralcodexten.substack.com/p/oh-the-places-youll-go-when-trying?token=eyJ1c2VyX2lkIjoxNTgzNTMyMiwicG9zdF9pZCI6MzQ1NzQ4OTcsIl8iOiJCMEpCZiIsImlhdCI6MTYxNzE5OTk3NiwiZXhwIjoxNjE3MjAzNTc2LCJpc3MiOiJwdWItODkxMjAiLCJzdWIiOiJwb3N0LXJlYWN0aW9uIn0.EbY4dONf-YZRlPsj3sxjDh3ay_oNa0tKR3xtE6K4_II Oh, The Places You'll Go When Trying To Figure Out The Right Dose Of Escitalopram: How high can you dose Lexapro before you stop getting extra benefit? And why is this such a hard question?"] AstralCodexTen (2021).
"16.7 mg Lexapro equals 20 mg of paroxetine (Paxil) or fluoxetine (Prozac). But the maximum approved doses of those medications are 60 mg and 80 mg, respectively. If we convert these to mg imipramine equivalents like the study above uses, Prozac maxes out at 400, Paxil at 300, and Lexapro at 120. So Lexapro has a very low maximum dose compared to other similar antidepressants. Why?
Because Lexapro (escitalopram) is a derivative of the older drug Celexa (citalopram). Sometime around 2011, the FDA freaked out that high doses of citalopram might cause a deadly heart condition called torsade de pointes, and lowered the maximum dose to prevent this. Since then it's been pretty conclusively shown that the FDA was mostly wrong about this and kind of bungled the whole process. But they forgot to ever unbungle it, so citalopram still has a lower maximum dose than every other antidepressant. When escitalopram was invented, it inherited its parent chemical's unusually-low maximum dose, and remains at that level today.
Now that we know the heart risk was overblown, should we increase the maximum dose to something closer to other SSRIs? Maybe not. Right now, escitalopram keeps showing up in studies and head-to-head comparisons as the most effective SSRI.
But if we're kind of under-dosing it, why should it work so well?"