It is estimated that 15% to 20% of people will suffer from depression during their lifetime. Antidepressant medications can be very helpful in treating depression, but since no single antidepressant works for everyone, medication adjustments are often necessary. These adjustments, or “second-step treatments,” may involve adding a second antidepressant or switching from the first medication to another.

Two new studies in the March 23, 2006 issue of the New England Journal of Medicine found that up to one-third of participants with major depression who were unsuccessfully treated with an initial antidepressant medication became virtually symptom-free after adding a second antidepressant or switching to a different one.

About the Studies

These studies involved 1,292 people with major depression who were participating in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The participants took the antidepressant citalopram, a selective serotonin reuptake inhibitor (SSRI) for up to 14 weeks, but either did not experience remission from depressive symptoms or could not tolerate the medication.

In one study, 565 of the participants received one of two antidepressant medications—bupropion (a non-SSRI medication) or buspirone (a medication that enhances SSRIs)—in addition to citalopram. In the other study, 727 of the participants switched from citalopram to one of three other antidepressants: bupropion, sertraline (an SSRI), or venlafaxine (similar to an SSRI, but also targets the neurotransmitter norepinephrine). The researchers used depressive symptom questionnaires to determine who experienced remission of depressive symptoms within 14 weeks of taking the second-step treatment.

Approximately 30% of the participants in both the citalopram plus bupropion and the citalopram plus busprione groups experienced remission of symptoms. But those taking citalopram plus bupropion experienced more symptom relief and were less likely to discontinue their medications due to adverse effects. Among participants who switched from citalopram to bupropion, sertraline, and venlafaxine, 21%, 18%, and 25%, respectively, experienced remission of symptoms. These differences were not significantly different from each other, and there were no significant differences among the three medications in terms of side effects.

Both studies were limited because they did not include a comparison group of participants who were taking a placebo. While there are ethical concerns associated with assigning a placebo to people with major depression, not having a placebo group makes it impossible to distinguish real effects of the medications from placebo effects (i.e., improvements in symptoms because participants expected to feel better).

How Does This Affect You?

These findings suggest that if an initial antidepressant prescription is unsuccessful, adding or switching to another medication may be helpful. Among participants who could not tolerate or did not respond to citalopram, approximately one in three experienced remission of symptoms after adding another antidepressant, and approximately one in four experienced remission after switching to another antidepressant.

This is encouraging for people who are suffering from depression, but have not yet responded to antidepressant medications. If you have been diagnosed with depression and are not responding to a particular antidepressant, talk with your doctor to find out if adding another medication or switching to a different one may benefit you. Future research will help determine why particular antidepressants work for some people but not others, which may help make treatment for depression more efficient.