Why Start with Two Antidepressants When One Will Do as Well?

Clinicians are sometimes tempted to initiate, or switch to, treatment with two antidepressants in patients with chronic or recurrent major depression episodes. To assess the merit of this strategy, researchers in a National Institute of Mental Health–funded, multisite, placebo-controlled, 7-month study randomized 665 patients with chronic or recurrent depression to one of three treatments:

• Escitalopram (10–20 mg/day) plus placebo (monotherapy)

• Sustained-release bupropion (150–400 mg/day) plus escitalopram

• Extended-release venlafaxine (37.5–300 mg/day) plus mirtazapine (15–45 mg/day)

Clinicians could vary doses according to patient response at scheduled intervals. Some study exclusions were lack of response to an FDA-approved monotherapy in the current episode or, in chronic depression, during the previous 2 years; lack of response to adequate trials of any study medication or combination; or use of a study medication at study entry.

Patients were moderately to severely ill, 75% had concurrent anxiety, and comorbid Axis I and Axis III disorders were common. After 12 weeks, no group differences were seen in rates of remission (37.7%–38.9%) or response (51.6%–52.4%). More adverse effects were seen in the venlafaxine+mirtazapine combination group than in other groups. After 7 months, results were essentially unchanged, with modest increases in remission (41.8%–46.6%) and response (57.4%–59.4%).