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STAR*D: Hope for Consumers with Major Depression
Access to a Range of Individualized Treatment Options is Key

Talking Points
March 23, 2006

Results of a landmark study on depression provide conclusive evidence that treatment works and recovery is very possible for people who suffer from major, chronic depression.  This study, called the “Sequenced Treatment Alternatives to Relieve Depression” study (STAR*D), is the largest multicenter study on major depression ever conducted.  It was funded by the National Institute of Mental Health (NIMH). 

Study results: The results of the study were released in two articles published in the March 23, 2006 issue of the New England Journal of Medicine.  The articles revealed that one in three individuals with major depression who had not previously experienced a remission of their symptoms using an antidepressant medication became symptom free (remission) after adding a second medication, and one in four became symptom free after switching to a different antidepressant.   The design and results speak to a common clinical issue that has important public health concerns given the severity of major depression on social, occupational, health, and family functioning.

Were different results achieved with specific medications?   No significant differences were found in the efficacy, safety or tolerability of the three medications administered to the group that switched medications.  These medications included sertraline (Zoloft), bupropion-SR (Wellbutrin) and venlaxafine-XR (Effexor), different types of anti-depressants.

Some differences in results were found in the two medications administered to the group that added a second medication.  Specifically, individuals administered bupropion-SR, an anti-depressant medication, experienced fewer symptoms, greater symptom relief and lower side effects than individuals administered buspirone, an anti-anxiety medication.  However, one-third of individuals became symptom free within 14 weeks of using either of these medications.

Does the failure of one Selective Serotonin Reuptake Inhibitor (SSRI) to work mean that others won’t work?

Not necessarily.  Significantly, some participants in the STAR*D study did not experience a reduction in symptoms when taking one SSRI (citalopram) but did experience reduction or full remission of their symptoms from a second SSRI (sertraline).  This does not mean that sertraline is generally more effective than citalopram but rather what works best for one person may not work as well for another.    

The results in STAR*D represent a significant step forward in the evolving understanding of how best to treat major depression.  These results should inform legislators and policymakers grappling with important public policy decisions at federal and state levels. 

  • Treatment works for many people with major depression - The results in this phase of the STAR*D study demonstrate that treatment for major depression is highly individualized – what works for one person may not work for another.  The results also demonstrate that just because a first treatment option doesn’t work doesn’t mean that a second treatment option won’t work.  Thus, it is critically important that individuals with major depression continuing working with their doctor to find a treatment that works. Notably, the STAR-D study focused not just on symptom reduction but also on the remission of symptoms - helping people regain their prior level of functioning. This is what all consumers and family members want and this study sets the bar where it should be.

In the words of John A. Rush, M.D., a principal investigator in the study, "Hang in there.  If the first treatment does not relieve your symptoms, consider changing or adding another medication.  Follow instructions from your doctor and don’t give up."

  • Limiting access to anti-depressant medications in private or public programs is "penny wise but pound foolish" - The results in this phase of the STAR*D study provide further conclusive evidence that arbitrary restrictions on access to anti-depressants and other psychiatric medications do not make sense.  Restrictions of this kind may prevent individuals with major depression from finding the medications that work best for them.  In the long-term, this does not save money but rather produces more suffering, lost productivity, increased hospitalizations, increased risks of suicide, and greater dependency on public benefits.
  • More research is needed - Although these results are promising, it is clear that more research is needed, both to better understand the impact of specific pharmacological and psychosocial treatments for major depression and to develop effective new treatments for alleviating the suffering caused by these brain disorders. The role of talk therapy - cognitive behavioral therapy is being explored in later study designs.  This is essential because to get the best results individuals needs to understand all the relevant choices among therapeutic options, and under what conditions to combine them for maximal results.

Proposed cuts to funding for the National Institute of Mental Health (NIMH) are ill-advised.  More funding for research is needed to build on the promise engendered by studies such as STAR*D.

  • Continued support of large longitudinal studies in “real world” settings is critically important - The STAR*D study is one of a group of four important NIMH supported   projects studying large groups of individuals with specific mental illnesses over extended periods of time in natural settings.  Others include the Clinical Antipsychotic Trials of Interaction Effectiveness (CATIE) on schizophrenia, Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), and Treatment for Adolescents with Depression Study (TADS).

These studies are unique and unprecedented.  As public, long-term, comparative, "real world" studies, they are different from those conducted by private industry.

They are essential to building a research and treatment "infrastructure" that can lead to newer, better medications and help consumers and family members and practitioners make better choices going forward. It is essential that   NIMH continue funding such studies to keep the momentum going.