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Depression Research

The STAR*D Study

New research reveals that, by working with their doctors and trying multiple treatment options, two-thirds of those with depression can become symptom-free.

Dr. A. John Rush (left) and Dr. Madhukar Trivedi

Dr. A. John Rush (left)
and Dr. Madhukar Trivedi,
both of the University of
Texas (UT) Southwestern
Medical Center and co-authors
of the STAR*D study.
Photo courtesy of University
of Texas

Research results from the largest clinical trial for depression ever conducted have helped scientists track "real-world" patients who became symptom-free and to identify those who were not helped by initial depression treatment. The results show that more than two-thirds of those suffering from major depression can become symptomfree, if they are willing to work with their doctors and try various treatments to determine which work best for them.

"The study offers clear evidence of what happens stepby- step," says Madhukar Trivedi, M.D., co-author of the study and professor of psychiatry at the University of Texas (UT) Southwestern Medical Center in Dallas. "And it gives us a good idea of what outcomes will be the following year, if patients continue the same treatment."

The study, funded by the National Institute of Mental Health (NIMH), used flexible adjustment of medication dosages, based on quick and easy-to-use ratings of symptoms, and the patients' own ratings of side effects.

"The take-home message for patients is to hang in there and stay in treatment, even if several steps and various medications must be tried," says A. John Rush, M.D., the principal investigator in the study, the vice chairman of clinical sciences, and professor of psychiatry at UT Southwestern. "Be patient and willing to tell your doctor if a medication isn't working, if the dosage is bothering you, or if you're having side effects. Collaborate with your physician to find the right medication and dosage for you, and stay on it long enough to give it a chance to work."

The trial was known as the STAR*D study—Sequenced Treatment Alternatives to Relieve Depression—and was conducted over six years. More information can be found at and at

Relief in Hours?

Dr. Carlos A. Zarate, Jr.

Dr. Carlos A. Zarate, Jr.,
Chief of Experimental
Therapeutics of the Mood
and Anxiety Disorders
Program at the National
Institute of Mental Health
Photo courtesy of NIH/NIMH

An experimental medication called ketamine relieves depression in just hours. Is it a key to the future of treatment?

Today's medications for depression take 4 to 6 weeks or longer to start working for most patients. But that long wait may become much shorter in the future.

A new study has revealed more about how a medication called ketamine, when used experimentally for depression, can relieve symptoms of depression in hours instead of weeks or months. Ketamine itself probably won't come into use as an antidepressant because of its side effects, notes lead researcher Carlos A. Zarate, Jr., M.D., Chief of Experimental Therapeutics of the Mood and Anxiety Disorders Program at the National Institute of Mental Health (NIMH). But the new finding moves scientists considerably closer to understanding how to develop faster-acting antidepressant medications.

"This may be a key to developing medications that eliminate the weeks or months patients have to wait for antidepressant treatments to kick in," says Dr. Zarate.

Ketamine works by blocking a receptor called NMDA on brain cells. A new 2007 study in mice reveals that this is just one of the steps involved. It turns out that ketamine blocks the NMDA receptor and increases the activity of another receptor, AMPA. Both of the receptors are binding sites for a chemical messenger in the brain called glutamate. This interplay of the two receptors appears to be crucial for ketamine's rapid actions.

"Our research is showing us how to develop medications that get at the biological roots of depression. This new finding is a major step toward learning how to improve treatment for the millions of Americans with this debilitating disorder; toward eliminating the weeks of suffering and uncertainty they have to endure while they wait for their medications to work," says NIH Director Elias Zerhouni, M.D.

Read More "Beating Depression" Articles
Beating Depression …Help Is Available / Working It Out / Depression Research

Summer 2007 Issue: Volume 2 Number 3 Page 13