Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report

Abstract

Objective: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method:A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N ϭ 3,671) to four (N ϭ 123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of Յ5 on the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR 16 ) (equivalent to Յ7 on the 17-item Hamilton Rating Scale for Depression [HRSD 17 ]) defined remission; a QIDS-SR 16 total score of Ն11 (HRSD 17 Ն14) defined relapse. Results: The QIDS-SR 16 remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. Conclusions: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.

A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression

“…The primary objective was to compare the efficacy of augmentation with risperidone vs. placebo in patients with difficult-to-treat depression, defined as patients who failed to respond or only partially responded to antidepressant monotherapy. We focused on difficultto-treat depression as a useful concept that may have more generalizability than TRD and, according to a recent STAR*D report, may be part of a continuum that leads to TRD (Thase et al, 2007;Rush et al, 2006). We selected 5 weeks as a lead-in period as it met the higher range of duration (3-5 weeks) defining an adequate treatment trial (Keller, 1988;Sackheim, 2001).…”

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

“…While 80% of patients will experience partial relief of depressive symptoms, complete remission occurs in only 50-60% of all cases despite treatment with multiple antidepressants (Nestler et al, 2002;Rush et al, 2006). Even in patients who respond to drug therapy, chronic treatmentFon the order of weeks or monthsFis required before antidepressants provide clinical benefit.…”

How Do We Re-Engage the Pharmaceutical Industry in Research on Serotonin and Psychiatric Disorders?

“…While newer antidepressants generally have fewer acute adverse effects and reduced overdose potential, their overall efficacy is still unacceptably low. 8 Pharmaceutical companies have therefore decided they cannot justify the huge investment they have been making in CNS research given the low likelihood of success in launching a safe drug with enhanced efficacy compared to the many other drugs already on the market. However, it is interesting that similar rates of failure are seen in other therapeutic areas, which are still being fully supported by pharmaceutical industry research (Figure 1).…”