Nefazodone and venlafaxine: two new agents for the treatment of depression.

Nefazodone and venlafaxine are two new antidepressants with pharmacologic actions and side-effect profiles that differ from those of the selective serotonin reuptake inhibitors (SSRIs). In addition to inhibition of serotonin reuptake, nefazodone exhibits 5-HT2 antagonism. Venlafaxine inhibits the reuptake of both norepinephrine and serotonin. Both appear to be effective and well tolerated in the treatment of major depressive disorder. Nefazodone differs from the SSRIs in that it does not cause sexual dysfunction or sleep impairment. Venlafaxine differs from the SSRIs because of its effects augmenting norepinephrine, as well as its demonstrated efficacy in the treatment of severely depressed, melancholic patients. Both drugs appear to hold significant promise as effective and well-tolerated medications for the treatment of major depression in the primary care setting.