an interesting drug. Rarely prescribed, but interesting.
It is older than what we typically give today. It
is an antidepressant with a twist.
order to understand why it is interesting, you need to know a little
bit about the pharmacology of the drug.
is a tricyclic antidepressant, in my book, or at least in my
head; but I have seen it referred to as a tetracyclic. It
depends on whether you think all the rings have to have an adjoining
side to count.
top diagram shows the antidepressant, amoxapine.
The second one shows a closely related drug, loxapine.
Except loxapine is not an antidepressant.
It is an antipsychotic. That one methyl
group on top makes all the difference…
main known mechanism of action for amoxapine is the inhibition of the
reuptake of norepinephrine.
It has a much smaller effect of inhibiting the reuptake of serotonin.
In that way it is similar to desipramine or nortriptyline, or
maprotiline, for that matter. But there is a twist.
Most drugs are altered in various ways before they are finally
eliminated from the body. Loxapine typically will have that
methyl group lopped off, turning it into amoxapine. So you
can’t give someone the antipsychotic loxapine, without the person also
getting some of the antidepressant, amoxapine. But wait,
Amoxapine is metabolized to two active metabolites, 7-hydroxyamoxapine
and 8-hydroxyamoxapine (ref.).
Both are active metabolites, and both inhibit reuptake of
norepinephrine. The twist is that 7-hydroxyamoxapine also
blocks D2 receptors. That means that loxapine has an active
metabolite that is an antidepressant, and the antidepressant has an
active metabolite that is an antipsychotic! Holy moley!
But that’s not all!
If you thought is was a good deal to get two drugs for the price of
one, wait ’til you hear this. Amoxapine also blocks 5-HT2
receptors. (As does loxapine.) So, not only is it
an antipsychotic, but it is an atypical
antipsychotic. Probably the cheapest
one there is, by an order of magnitude.
Now, to get to the point of this post: when would a clinician pick
amoxapine as an antidepressant to prescribe to someone?
If a patient has depression with psychotic features, it would be an OK
choice. In general, we don’t want to expose people to
antipsychotics unless there is a good reason to. Depression
with psychotic features typically does not respond well to an
antidepressant without an antipsychotic.
Also, because amoxapine is so distinctly different from other
antidepressants, it is really in a class of its own. Thus, it
could be considered as a treatment for patients who have had adequate
trials of several other antidepressants, without good results.
As a tricyclic antidepressant, it has the disadvantages I’ve already
noted in the post about amitriptyline.
(This post is not really intended to stand alone, you might want to
read the more abstract posts I wrote on the topic of selection of
antidepressants. They can be found by clicking on the
Category link in the sidebar for antidepressants.)