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Stanford Report, May 24, 2000

Fighting chronic depression: Two therapies better than one

BY CAROLINE SEYDEL

Conventional wisdom among psychiatrists has dictated that people suffering from chronic depression are best treated with a combination of antidepressants and psychotherapy. Now, a large national study confirms that combination therapy is more effective than either medication or counseling alone.

The study, published May 18 in the New England Journal of Medicine, shows that the antidepressant nefazodone hydrochloride (Serzone) combined with psychotherapy specifically designed for chronic depression offers the best treatment for people suffering from this long-term form of depression.

This study is the largest ever undertaken comparing medication alone, psychotherapy alone, or combination treatment for chronic depression, according to the researchers. Bristol-Myers Squibb Co., makers of Serzone, funded the research.

"This is the first study that's been large enough to adequately test whether combination treatment is truly superior to medication or psychotherapy alone," said study co-author Bruce Arnow, PhD, assistant professor of psychiatry and behavioral sciences at Stanford.

In the study, 681 depressed patients were randomly assigned to one of three treatment options. Patients assigned to the drug-only group took nefazodone alone, therapy-only patients received psychotherapy tailored to chronic depression, and combination patients were given both simultaneously. After 12 weeks, significantly more patients who received the combination of therapies had improved compared with patients receiving either single treatment.

At any given time, 3 percent of the U.S. population suffers from chronic depression. Chronically depressed individuals are hospitalized more often, require more health care, and attempt suicide more frequently than those suffering from episodic depression. They have more severe problems with work, family and social relationships. In their paper, the researchers assert that "chronic depression accounts for an inordinate portion of the enormous illness burden associated with depression."

"It's a major public health problem in this country," Arnow said, "and this [study] sheds important light on the most appropriate treatment for this group of patients."

Study participants included adult men and women of varying ages who scored 20 or greater on the Hamilton Rating Scale for Depression (HAM-D). The HAM-D assesses the severity of depression in patients who are already diagnosed with depression. The higher the score, the more severe the depression. A score of below 8 is considered normal; the average score of patients at the start of the study was 27.

Among patients who completed 12 weeks of combination therapy, 85 percent reduced their HAM-D score by at least half. For both drug-only and therapy-only patients, only about 50 percent reduced their score by that much.

"Patients in this study had been suffering major depression for an average of eight years," Arnow noted. "Many had been suffering for 20 years or more, so the response to combination treatment of 12 weeks is very striking."

The psychotherapy used in the study, Cognitive Behavioral Analysis System of Psychotherapy, or CBASP, is the first psychotherapy developed specifically to treat chronic depression. It teaches patients to focus on how their thinking and behavior affect their interpersonal interactions and to apply a specific problem-solving technique to improve their functioning in interpersonal situations.

Few therapists are trained in CBASP, however, and Arnow hopes the results of this study will spur efforts to provide psychotherapists with more opportunities to learn it, making it more widely available.

The antidepressant studied, used alone or in combination with psychotherapy, was associated with an earlier response than psychotherapy alone. Patients did not experience significant sexual dysfunction or weight gain, both common side effects of antidepressant medications.

The results for both single treatments were comparable to those found for antidepressants in prior studies of patients with chronic depression. However, Arnow noted, the results of the current study cannot be generalized to other antidepressants used in combination with psychotherapy or forms of psychotherapy other than CBASP until they have been tested in clinical trials and shown similar response rates.

The study also included a four-month continuation trial for patients who responded to medication alone, psychotherapy alone or combination treatment. This was followed by a 52-week maintenance phase evaluating either the drug versus placebo or monthly psychotherapy. The data from these two phases are still being evaluated.

A key strength of the study is that researchers at all sites found the same results, Arnow said. "The fact that the pattern of results didn't vary from site to site makes the findings all the more compelling."

In addition to Arnow, contributing researchers at Stanford include Alan Schatzberg, MD, professor and chair of psychiatry and behavioral science; Rachel Manber, MD, assistant professor of psychiatry and behavioral science; and Lorrin Koran, MD, professor of psychiatry and behavioral science.

Other study sites included Brown University; Medical College of Virginia & Virginia Commonwealth University; State University of New York, Stonybrook; Cornell University Medical College; Emory University School of Medicine; University of Texas Medical Branch at Galveston; University of Texas Southwestern Medical Center at Dallas; Rush-Presbyterian-St. Luke's Medical Center, Chicago; University of Washington, Seattle; University of Arizona, Tucson; and Western Psychiatric Institution and Clinic, University of Pittsburgh.

Many of the principal investigators were consultants and received honorariums from Bristol-Myers Squibb or serve on the company's scientific advisory board. Most also have similar relationships with other firms that manufacture FDA-approved treatments for depression. SR