In spite of the range of medications now available, major depression remains a challenging disease to treat. Only about half of adult patients respond to the first antidepressant they try, with only one-third achieving remission, reports the August 2008 issue of the Harvard Mental Health Letter. Most adults will try two or more medications before finding one that alleviates their depression.

When the first antidepressant doesn’t provide adequate relief, patients and their clinicians face a challenging decision. Although two broad strategies exist—switching to a new drug or augmenting the first drug with a second—it hasn’t been clear which is best.

Over the past few years, new research has helped fill this gap in knowledge. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, the largest prospective study of successive treatment options ever conducted, looked directly at the question of what to do when the first medication fails. STAR*D results indicate that either switching medications or adding a second drug is equally effective. The study also showed that, with persistent trial and error, nearly seven in 10 adult patients with major depression will eventually find a treatment that works.

Dr. Michael Miller, editor in chief of the Harvard Mental Health Letter, notes that there is no one-size-fits-all solution when a first antidepressant fails to alleviate symptoms, because individuals vary so greatly in their response to medications. But as researchers identify and test additional treatment options, they hope to improve the odds of success.