How antidepressants help depression: mechanisms of action and clinical response

The monoamine hypothesis of depression suggests that depressive symptoms can be moderated by enhancing monoamine neurotransmission. Targeted neurotransmitters include serotonin and norepinephrine, and a number of medications are available that can selectively enhance the actions of one or both of these substances. Although laboratory tests have validated the pharmacologic effects of these compounds, much less is known about how these effects translate into clinical response. Therapeutic research and experience show clearly that the medications help patients, although the individual and potential cooperative or complementary effects of stimulating each neurotransmitter system remain unclear. Depletion studies have reinforced the validity of targeting these systems and, at the same time, underscored that monoamines most likely are not the only factor driving the clinical presentation of depression.