Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report
Comprehensive Overview
Published in the American Journal of Psychiatry in 2006, this report from the STAR*D trial asked how depressed patients who need several rounds of treatment before finding one that works actually fare, both in the short term and over the following year, since prior research on treatment-resistant depression had rarely tracked patients through more than one or two treatment attempts. Researchers followed a broadly representative group of outpatients with nonpsychotic major depressive disorder, all starting with citalopram, and moved those who did not achieve remission or could not tolerate a given medication to a new treatment step, up to four steps in total, using a measurement-based care approach with regular symptom monitoring to guide dose adjustments and treatment changes. Across the four steps, the number of participants ranged from 3,671 at step one down to 123 who reached the fourth step. Patients who reached an adequate benefit, ideally full symptom remission, could then enter a 12-month follow-up phase to track whether their improvement held. The topline result was that remission rates fell substantially with each additional treatment step required, while relapse rates during follow-up rose correspondingly among those who had needed more steps to get better.
Outcomes and Implications
The most important finding was that remission rates dropped sharply with each successive treatment step: 36.8% of patients remitted on their first treatment attempt with citalopram, 30.6% remitted at the second step, but only 13.7% remitted at the third step and 13.0% at the fourth, showing that patients who fail two treatments face a substantially steeper climb toward recovery than those just starting out. Despite this decline, the cumulative remission rate across all four steps combined reached an estimated 67%, meaning most patients who stayed in treatment through multiple attempts eventually did get better, even if later steps individually helped fewer people. The time needed to reach remission also grew longer at later steps, ranging from about 5.4 weeks at the earliest steps to 7.4 weeks by the fourth. During the 12-month follow-up phase, relapse proved significantly more common among patients who had required more treatment steps, regardless of whether they entered follow-up in full remission or with only partial improvement, and full remission at follow-up entry consistently predicted a better long-term outcome than partial improvement alone, underscoring remission, not just symptom reduction, as the meaningful treatment goal. The authors conclude that when patients require additional treatment steps to reach remission, clinicians should expect both lower rates of success and higher rates of relapse afterward, and they call for further research to identify the most effective sequences of multistep treatment and for the development of more broadly effective antidepressant therapies overall.