https://astralcodexten.substack.com/p/oh-the-places-youll-go-when-trying

 

I.

What is the right dose of Lexapro (escitalopram)?

The official FDA packet insert recommends a usual dose of 10 mg, and a maximum safe dose of 20 mg. It says studies fail to show 20 mg works any better than 10, but you can use 20 if you really want to.

But Jakubovski et al's Dose-Response Relationship Of Selective Serotonin Reuptake Inhibitors tries to figure out which doses of which antidepressants are equivalent to each other, and comes up with the following suggestion (ignore the graph, read the caption)

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 [edit: I got the timing messed up, see here]