How Antidepressants Help Depression: Mechanisms of Action and Clinical Response

The monoamine hypothesis of depression suggests that depressive symptoms can be moderated byenhancing monoamine neurotransmission. Targeted neurotransmitters include serotonin and norepinephrine,and a number of medications are available that can selectively enhance the actions of one orboth of these substances. Although laboratory tests have validated the pharmacologic effects of thesecompounds, much less is known about how these effects translate into clinical response. Therapeuticresearch and experience show clearly that the medications help patients, although the individual andpotential cooperative or complementary effects of stimulating each neurotransmitter system remainunclear. Depletion studies have reinforced the validity of targeting these systems and, at the sametime, underscored that monoamines most likely are not the only factor driving the clinical presentationof depression.