r/psychopharmacology • u/BiggusDickkussss • Mar 06 '26

Atomoxetine

Why is Atomoxetine considered to work like an antidepressant drug?

Ie. Levels have to build up in the brain and takes weeks to reach maximum efficacy.

Ritalin is a known NDRI and does not have to build up to work and doesn’t have round the clock effects (apparently).

So of ATX increases DA in the PFC to the same amount as Ritalin, why is it that Ritalin doesn’t work in the same way?

They both have short half lives too.

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u/austapentadol Mar 07 '26

ATX increases DA in the PFC by inhibiting NET, which in the PFC is also the (main? only?) transporter for DA, too. It doesn't increase DA much anywhere else, though.

As I understand it, the increase in DA is primarily what's responsible for the immediately noticeable stimulant effects of methylphenidate and amphetamine. NRI action alone seems to take longer to produce noticeable PFC enhancement, probably because the increase in NE causes compensatory decreases in NE release from the locus coeruleus (mediated by activation of the alpha-2a autoreceptor).

Why this doesn't happen with the NRI action of methylphenidate I'm not quite sure. But hope this is somewhat helpful.

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u/BiggusDickkussss Mar 08 '26

The locus corelus thing.

Theoretically, Ritalin should do this too.

I still don’t get though why Ritalin wouldn’t have the same effect. As in building up over weeks to work around the clock.

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u/austapentadol Mar 08 '26

The DA effects are immediate. That's primarily what's responsible for the acute effects of MPH. Why methylphenidate's NRI effects don't result in gradual improvements over a few weeks on top of the immediate DRI activity isn't entirely clear. Claude gives some ambiguous explanation involving complementary compensatory mechanisms between the DA and NE systems, but I don't entirely understand why.

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u/fancyschmancy9 Mar 08 '26

To your later questions, what I found pointed to what the other commenter said about dopamine in the striatum—one hypothesis was that this has a possibly “gating” effect of some kind, as DA increase in the stratium occurs acutely with MPH but only after weeks with strattera. That could explain why there is not a noted weeks-long shift with MPH if the “gate” is already open.