December 7, 2007

VUMC Reporter Series: Taking the lead in analyzing treatments for depression

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VUMC Reporter Series: Taking the lead in analyzing treatments for depression

Richard Shelton, M.D., directs the Division of Adult Psychiatry. (photo by Neil Brake)

Richard Shelton, M.D., directs the Division of Adult Psychiatry. (photo by Neil Brake)

Vanderbilt University has established itself as a premier location for depression research, especially in comparing how to best treat patients who suffer from this common, yet debilitating disease affecting more than 17 million adults annually.

Antidepressant medications are the most widely used treatment for major depressive disorder in the United States, but until recently there has been very little hard analysis of the treatments of depression — medications, psychotherapy, or a combination of both.

But over the past decade, with 8 percent of the population now having a major depressive episode at some point in their life, there has been an explosion of research in developing a real evidence base for treatments of depression.

“There are as many psychotherapies as there are stars in the sky,” said Richard Shelton, M.D., director of the Division of Adult Psychiatry. “But they are different variations of psychological treatments, with very little evidence supporting their effectiveness.”

One of the largest trials conducted recently was led by Shelton and his colleague Steven Hollon, Ph.D., professor of Psychology in Vanderbilt's College of Arts and Science, a multi-center trial comparing the efficacy of antidepressant medications with cognitive behavioral therapy (CBT) in treating moderate to severe depression.

The study was funded by the National Institute of Mental Health, and was based on the theory that there was substantial evidence that antidepressant medications worked, but less data on cognitive therapy.

The study, published in the April 2005 Archives of General Psychiatry looked at 240 outpatients in Nashville and Philadelphia, age 18-70, with moderate to severe depression. The patients were assigned to one of three groups — 16 weeks of the anti-depressant Paroxetine; 16 weeks of cognitive therapy; or eight weeks of placebo.

What they found surprised many — that cognitive therapy can be just as effective as medications for the initial treatment of moderate to severe major depression, but the degree of effectiveness may depend on a high level of therapist experience or expertise.

Another paper, published in the same issue of the journal, showed that cognitive therapy has an enduring effect that extends beyond the end of treatment. It seems to be as effective as keeping patients on medication.

“What we really want to do is establish whether there is added value of cognitive therapy over and above medication alone — adding cognitive therapy to medication. Realistically, that's what happens to most people — many don't just get psychotherapy alone,” Shelton said. “Once you get to a moderate level of severity, most people get medication, and may have psychotherapy added to that. Thus far, it looks like there is some added value of adding psychotherapy.”

Shelton says that Vanderbilt's Department of Psychiatry is going through a process of re-examining and, in fact, returning to the practice of training psychiatrists how to do psychotherapy properly.

“The field sort of drifted away from psychological treatments for a long time, but now we're seeing a push back. Not that psychiatrists are ever going to go back to doing mostly psychoanalysis, but rather psychiatrists will be doing a combination of both medication and psychological treatment.”

Shelton says it's also important to set standards for training therapists how to do psychotherapy. “If you consider at least 5 to 6 percent of the population is seriously depressed at any given time, you're talking about millions of people. If you just multiply that by the number of therapists required to deal with this, the numbers stop adding up. We want to train people and promulgate standards, but we also want to go forward in a realistic manner,” Shelton said.

One alternative to CBT that is being studied at Vanderbilt and other institutions is Behavioral Activation Therapy — a type of therapy which focuses on changing behaviors to address problems people might be experiencing. Hollon has been working with researchers at the University of Washington, and the findings have shown that it is much less complicated to administer, easier to train therapists to do, and works about as well as CBT.

“You can train a lot of people to do it, and not necessarily people who have a doctorate level of training. Most people get their treatments by master's-prepared therapists, not Ph.D.-level therapists,” Shelton said. “However, we need more research support before recommending that it be used widely.”

Shelton said that Vanderbilt depression research has also focused on how depression can adversely affect the outcome of many diseases. The research has focused on the two hypotheses, the first being that depression negatively impacts the ability of patients to follow through with treatment.

“This has been a huge issue with diseases like diabetes,” he said. “If you are hardly able to get out of bed, you're probably not going to be able to be monitoring your blood sugar and taking your insulin properly,” he said.

A second hypothesis is that when people are depressed they activate the stress response axis, which increases the amounts of cortisone in the body. Cortisone is critical to clotting, inflammatory disease response, lipid levels and the proliferation of cancer.

“This is an area that we are going to be seeing a great deal of focus on in the coming years,” he said.

Shelton is the James G. Blakemore Professor and Vice Chair for Research in the Department of Psychiatry.