SNRIs

Venlafaxine, desvenlafaxine, duloxetine, milnacipran and levomilnacipran block both the serotonin and the noradrenaline transporter. The ratio between the two is not fixed across the family, and for venlafaxine it is not fixed across the dose either — largely serotonergic low down, noradrenergic higher up, so the same tablet is a different drug at a different dose.

They carry the antidepressants' serotonin syndrome risk in full and add a noradrenergic one: blood pressure rises, and stimulants push the same lever from the other side. Venlafaxine has the worse overdose picture of the group, with seizures and cardiac effects rather than a purely serotonergic one. Duloxetine inhibits CYP2D6, which matters for anything that needs that enzyme to become active or to be cleared. Discontinuation from the short-acting members is abrupt and physical.