Venlafaxine is the first member of a novel class of antidepressants that inhibits the reuptake of both serotonin and norepinephrine. Clinical trials of venlafaxine have demonstrated its efficacy and safety in the treatment of patients diagnosed with major depression. Because patients who have depression also often have anxiety, recent investigations have focused on determining whether venlafaxine can relieve symptoms of anxiety in depressed patients. We performed a pooled analysis of six short-term trials of venlafaxine, retrospectively measuring anxiety in anxious depressed patients using the Hamilton Rating Scale for Depression (HAM-D), Anxiety/Somatization factor and Anxiety Psychic item scores. Three studies were placebo-controlled, and three were placebo- and active-drug-controlled; active controls were imipramine in two trials and trazodone in the third trial. Patients were categorized as having anxiety accompanying depression if baseline HAM-D Anxiety Psychic item scores were 2 or greater. Anxious depressed patients treated with venlafaxine showed greater improvement than those treated with placebo beginning at week 3, according to the HAM-D Anxiety/Somatization factor score, and beginning at week 1, according to the Anxiety Psychic item score. Both effects were maintained at week 6 of treatment (and at week 12 in the one study of longer duration). Finally, treatment with venlafaxine resulted in a highly significant (p < or = 0.001) improvement in depression scores in patients who were anxious at baseline, compared with placebo-treated patients. The results of this analysis demonstrate that venlafaxine is more effective than placebo in reducing symptoms of anxiety in depressed patients and suggest that venlafaxine may afford a monotherapy option for treating patients who have a comorbid diagnosis of depression with anxiety.