New Strategies Help Depressed Patients Become Symptom-Free
Results of the nation’s largest depression study show that one in three depressed
patients who previously did not achieve remission using an antidepressant became
symptom-free with the help of an additional medication and one in four achieved
remission after switching to a different antidepressant. The study, funded by
the National Institutes of Health’s National Institute of Mental Health (NIMH),
shows that people whose depression is resistant to initial treatment can achieve
remission — the virtual absence of symptoms — when treated with a
second strategy that either augments or switches medications. This is the first
study to examine the effectiveness of different treatment strategies for those
who did not become symptom-free after initial medication.
John Rush, M.D., and Madhukar H. Trivedi, M.D., of the University of Texas Southwestern
Medical Center (UTSWMC), and colleagues report on the first major results of
the clinical trial, known as the STAR*D (Sequenced Treatment Alternatives to
Relieve Depression) study, in two papers published in the March 23, 2006 issue
of the New England Journal of Medicine.
“These findings provide important treatment options to mental health clinicians
and the millions of Americans who struggle with treatment-resistant depression,” said
NIH Director Elias A. Zerhouni, M.D.
Patients who did not experience a remission of symptoms during the first level
of the Star*D study — in which they initially took the antidepressant citalopram,
a selective serotonin reuptake inhibitor (SSRI), for up to 14 weeks — were
eligible to enter level 2 of the trial where they were offered additional treatment
options designed to help them become symptom-free.
“If the first treatment attempt fails, patients should not give up,” said NIMH’s
director Thomas Insel, M.D. “By remaining in treatment, and working closely with
clinicians to tailor the most appropriate next steps, many patients may find
the best single or combination treatment that will enable them to become symptom-free.”
The 1,439 patients who were eligible and volunteered to enter level 2 were presented
with seven different treatment options. Only very few participants said that
all of the choices were equally acceptable and allowed themselves to be randomly
assigned to any one of them. All the rest of the participants identified at least
one of the treatments as being unacceptable, and chose to limit the treatments
to which they would allow themselves to be randomly assigned. Fifty-one percent
(727) of the patients chose options that included switching to a different medication
and were randomly assigned to one of the three switch medications. Thirty-nine
percent (565) chose options that included augmenting the citalopram they were
already taking, and were randomly assigned to one of the two augmenting medications.
The 727 patients who received the switch medication treatments were randomized
to take one of three medications currently available and used in practice — sertraline
(an SSRI that targets the neurotransmitter serotonin), bupropion-SR (a non-SSRI
antidepressant), or venlafaxine-XR (an agent that targets serotonin and norepinephrine,
another neurotransmitter).
Rush and colleagues found that 25 percent of the patients who switched to a
new medication became symptom-free within 14 weeks; this was similar within each
of the three treatment groups. Additionally, no significant differences were
found in the efficacy, safety or tolerability of the three medications to which
patients were switched.
“Contrary to what previous research suggests, this study shows that all three
medications the patients switched to, despite having different mechanisms of
action, appear to be useful options for treating depression following failure
on the first SSRI,” said Rush. “The results provide patients and doctors with
important information that intolerance or lack of efficacy with one SSRI seems
not to predict the same with another.”
The 565 patients who received the augment medication were randomized to take
either bupropion-SR (a non-SSRI antidepressant) or buspirone (a medication that
enhances the action of an SSRI) in addition to the SSRI citalopram that they
were already taking in Level 1. Within 14 weeks of using either treatment, about
one third of the patients who enrolled in the augmentation study became symptom-free,
Trivedi and colleagues reported. Both combinations appeared similar in terms
of remission; however, those who augmented citalopram with bupropion-SR experienced
fewer symptoms, a greater degree of symptom relief and lower side effects compared
to those who augmented with buspirone.
“Augmenting the first medication may be an effective way for people with depression
to become symptom-free,” said Trivedi. “Augmenting earlier in the course of treatment,
or perhaps prescribing a combination of drugs to patients initially, may be more
effective than using one treatment alone.”
According to the researchers, the switch and augment treatments cannot be directly
compared because of the way the trial was designed. The results, however, can
be used to help guide treatment choices within each group; it also may be that
different people respond better to one as opposed to another treatment.
“Further research may help customize the treatment to the individual patients,” says
Rush. Study participants who still did not achieve remission in level 2 had the
option of completing up to two additional levels of treatment. Results from levels
3 and 4 of the STAR*D trial will be published later this year.
STAR*D is part of an overall NIMH effort to conduct practical clinical trials
in “real world” settings that address public health issues important to those
persons affected by major mental illnesses.
Other study authors include:
- Stephen Wisniewski, Ph.D., University of Pittsburgh
- Andrew Nierenberg, M.D., Massachusetts General Hospital
- Diane Warden, Ph.D., University of Texas Southwestern Medical Center
- Louise Ritz, M.B.A., NIMH
- Barry Lebowitz, Ph.D., University of California, San Diego
- Kathy Shores-Wilson, Ph.D., University of Texas Southwestern Medical Center
- Melanie Biggs, Ph.D., University of Texas Southwestern Medical Center
- Maurizio Fava, M.D., Massachusetts General Hospital
- Jonathan W. Stewart, M.D., Columbia University
- Michael E. Thase, M.D., University of Pittsburgh
- James F. Luther, M.A., University of Pittsburgh
- George Niederehe, Ph.D., NIMH
- Frederick Quitkin, M.D., Columbia University
For more information on STAR*D level 2, visit:
For more information on STAR*D level 1, visit:
For general information on the STAR*D study, visit:
NIMH is part of the National Institutes of Health (NIH), the Federal Government's
primary agency for biomedical and behavioral research. NIH is a component of
the U.S. Department of Health and Human Services.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov. |