STAR D

Sequenced Treatment Alternatives to Relieve Depression (STAR*D)
Specialty	Psychiatry
Symptoms	Major depressive disorder
Treatment	Antidepressants, psychotherapy

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study is a large-scale, multi-phase clinical trial designed to evaluate the effectiveness of different treatment strategies for patients with major depressive disorder (MDD) who do not respond to initial antidepressant therapy. Conducted in the United States and funded by the National Institute of Mental Health (NIMH), STAR*D is one of the largest and most comprehensive studies of its kind.

Background

Major depressive disorder is a common and debilitating mental health condition characterized by persistent feelings of sadness, loss of interest in activities, and a range of physical and emotional problems. Despite the availability of numerous antidepressant medications, a significant proportion of patients do not achieve remission with their first treatment. The STAR*D study was initiated to address this challenge by exploring various treatment sequences and combinations.

Study Design

The STAR*D study was structured in four levels, each representing a different step in the treatment process for patients who did not achieve remission or could not tolerate the treatment at the previous level.

Level 1

All participants began treatment with citalopram, a selective serotonin reuptake inhibitor (SSRI). The goal was to determine the effectiveness of this common first-line treatment.

Level 2

Patients who did not achieve remission in Level 1 were randomized to one of several options, including switching to a different antidepressant (such as sertraline, bupropion, or venlafaxine) or augmenting citalopram with another medication (such as buspirone or bupropion).

Level 3

For those who did not respond in Level 2, further options included switching to another antidepressant (such as mirtazapine or nortriptyline) or augmenting with lithium or triiodothyronine (T3).

Level 4

The final level involved more intensive treatments, such as switching to tranylcypromine, a monoamine oxidase inhibitor (MAOI), or a combination of venlafaxine and mirtazapine.

Results

The STAR*D study found that approximately one-third of patients achieved remission with the initial treatment of citalopram. For those who did not respond, subsequent treatment steps provided additional opportunities for remission, with cumulative remission rates increasing with each level. However, the likelihood of remission decreased with each successive treatment step.

Implications

The findings from STAR*D have significant implications for the treatment of major depressive disorder. They highlight the importance of personalized treatment strategies and the need for clinicians to be prepared to try multiple treatment options to achieve remission in patients with depression.

Criticisms and Limitations

Despite its contributions, the STAR*D study has faced criticism regarding its complex design, the generalizability of its findings, and the challenges in interpreting its results due to the open-label nature of the study and the lack of a placebo control.

Also see

• Major depressive disorder
• Antidepressant
• Psychotherapy
• Selective serotonin reuptake inhibitor
• National Institute of Mental Health