STAR*D Trial: Third antidepressant medication might help in treatment-resistant depression
Jul 10, 2006 - 9:00:37 PM

The next wave of results from the nation's largest real-world study of treatment-resistant depression shows that patients had a moderate chance of becoming symptom-free when they switched to a third antidepressant medication, following two previously unsuccessful medication attempts. These results from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, funded by NIMH, were published in the American Journal of Psychiatry on July 1, 2006.

During Levels 1 and 2 of the STAR*D trial, which started with 2,876 participants, about half of all patients became symptom-free. Of the other half, about one in five became symptom-free when they went on to Level 3 and switched medications again.

"STAR*D continues to provide valuable real-world information about treating depression," said NIMH Director Thomas R. Insel, M.D. "Not only are the results enlightening, but they are telling us that more research is needed to help people with this debilitating illness, especially those who have tried several treatments and the treatments have failed."

As in Level 2, patients in Level 3 were given the choice of either switching medications or adding another medication to their existing medication; 234 patients chose to switch medications in Level 3. The results for those who chose to add to their existing medication will be available later in 2006.

The patients were randomly assigned to take either mirtazapine (Remeron), an "atypical" antidepressant, or nortriptyline (Aventyl or Pamelor), a tricyclic antidepressant, for up to 14 weeks. Both work differently in the brain than the selective serotonin reuptake inhibitors (SSRIs) and other medication used in Levels 1 and 2 of the STAR*D trial.

Overall, the two medications were about equally effective with 10 to 20 percent of patients becoming symptom-free. The type and severity of side effects were similar for both medications. In addition, neither medication resulted in a faster improvement rate than the other, suggesting that no clear advantage exists for either medication.

"Patients who do not respond to two consecutive antidepressant trials should not give up. Many of them will get better if they keep trying different treatment regimens or combinations, although the benefits from a third trial of an antidepressant alone appear to be rather modest," said lead author Maurizio Fava, MD, of the Massachusetts General Hospital in Boston.

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