Roughly one quarter to one third of people who do not achieve full remission of symptoms with an initial antidepressant become symptom-free after changing to or adding a second antidepressant, according to a pair of articles in the March 23 issue of the New England Journal of Medicine.

Phase two results of the four-phase STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study --- the largest of its kind --- are derived from real-world treatment of nearly 3,000 patients at 41 US primary-care and psychiatric clinics. The six-year study is funded by the National Institute of Mental Health.
A. John Rush, MD, principal investigator of one study and lead author of an article said, “For a depressed individual, it may not matter so much what drug is being prescribed, but that the person moves forward and keeps trying.”

In phase one of the study, participants were treated with citalopram hydrobromide for up to 14 weeks. A “measurement-based care” approach was used, whereby patients’ symptoms and medication side effects were evaluated at each visit based on certain guidelines, with dosages modified as needed.

At the end of phase one, about one third of participants were symptom-free. The two thirds who did not achieve remission could select from several treatment options ? including whether to change medications or continue using citalopram and add a second medication. Of those, 1,429 continued in the study.

The patients who chose to switch medications were randomized to one of three antidepressants: bupropion hydrochloride-SR, sertraline hydrochloride or venlafaxine hydrochloride-XR. Of those, approximately 25 percent achieved remission of symptoms within 14 weeks, with no significant differences in efficacy, safety or tolerability among the three drugs.

Participants who decided to add a medication were given either bupropion hydrochloride-SR or buspirone hydrochloride, along with citalopram, which they were already taking. Within 14 weeks, 30 percent of these patients became symptom-free, with neither medication combination statistically different in effectiveness on primary outcomes.

“These results show that augmenting a first antidepressant with a second one may be worthwhile for some patients and might be considered even earlier for some people,” said Madhukar Trivedi, MD, lead author of the second article.

“If you add together the people who achieved remission in both phase one and phase two of STAR*D, you see that more than 50 percent of participants become symptom-free after one or two treatments,” Trivedi said. “That is exciting. If you compare this to the vast majority of other chronic medical diseases, getting to remission in this large percentage is good news.”

Trivedi said the study also points to the need for further research to help customize treatments to individual patients. Results of phases three and four of the STAR*D study are expected to be published later this year, he said.