Although grouped with the tricyclic antidepressants (TCAs), amoxapine (Asendin) is actually a tetracyclic antidepressant (TeCA) by structure with four hydrocarbon rings. Amoxapine is rarely prescribed. It is the least anticholinergic of all TCAs.
Amoxapine is one of two antidepressants (trimipramine) that block D2 dopamine receptors. Dopamine antagonism gives amoxapine weak antipsychotic properties as well as risk of extrapyramidal symptoms (EPS) and prolactin elevation. The first-generation antipsychotic (FGA) loxapine (Loxitane) is metabolized to amoxapine. Note that other drugs with the -pine suffix are antipsychotics (olanzapine, quetiapine, clozapine, asenapine, etc).
Out of 71 single-drug exposures reported to Poison Control, there 7 major serious outcomes including 1 death (Nelson & Spyker, 2017). This is a high mortality index, but due to small sample size it is undetermined whether amoxapine is actually more dangerous than the average TCA. Regardless, a bottle of amoxapine may provide the suicidal patient “ammo to ascend” to heaven.
Dosing: Target dose for depression is 200–300 mg HS or in divided doses; The label recommends starting at 50 mg BID–TID; Max is 400 mg/day if outpatient (600 mg/day if inpatient); Divide doses > 300 mg daily; Taper gradually to stop.
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