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Depression is often related to disturbances of norepinephrine and serotonin neurochemical systems within the brain that affect functional neurobehavioral systems. Classes of antidepressant agents have been developed that directly affect proposed brain neurochemical alterations. Many of the differences among antidepressant agents, particularly in safety and tolerability, can be attributed to their differing effects on receptor blockade and neurotransmitter reuptake. The overall goal of antidepressant treatment is complete recovery, and three phases of treatment have been delineated. Because of the recurrent and potentially chronic nature of depression, safety and tolerability of available treatments are especially important. An overview of antidepressant options is presented, with a particular focus on venlafaxine.