Drug therapy for depression Several drug classes and drugs can be used to treat depression: Selective serotonin reuptake inhibitors (SSRIs) Serotonin modulators (5-HT 2 blockers) Serotonin-norepinephrinereuptake inhibitors Norepinephrine-dopaminereuptake inhibitor Heterocyclic antidepressants Monoamine oxidase inhibitors (MAOIs) Melatonergic antidepressant Ketamine-like drugs Choice of drug may be guided by past response to a specific antidepressant.