``We were stunned'' that 85 percent of patients who completed 12 weeks of treatment showed a good response or even remission, said Dr. Martin B. Keller of the Brown University School of Medicine.

The work shows ``chronic depressive disorders are treatable,'' he told a news conference. Keller is to report the initial findings of the study Wednesday at the American Psychiatric Association's annual meeting.

The study, carried out at a dozen medical centers, was paid for by Bristol-Myers Squibb Co. The company makes Serzone, the antidepressant used in the work.

Keller said it would be reasonable to study whether a drug other than Serzone would work as well in combination with the psychotherapy.

Herbert C. Schulberg, a psychologist at the University of Pittsburgh School of Medicine who was familiar with the results, called them impressive.

``It does point to a direction to be pursued,'' he said in a telephone interview.

Researchers are continuing the study to determine the long-term effects.

The study began with 681 people who had depression for at least two years. Half the participants had been ill for more than 20 years, and most had never had an adequate attempt at treatment, Keller said. Their average age was the early 40s.

The participants were randomly assigned to one of three groups: Serzone only, psychotherapy only, or a combination.

The psychotherapy, called the Cognitive Behavioral Analysis System of Psychotherapy, was developed especially for chronic depression but is not widely used. Patients focus on specific troublesome situations, learn how to solve their problems in relating to other people and take responsibility for the consequences of their behavior.

Participants assigned to the psychotherapy got 16 to 20 sessions over the 12-week treatment period. Those assigned to Serzone, also called nefazodone, took it twice a day.

During the 12 weeks, about 25 percent of patients dropped out of each of the three treatment groups, a low loss for such studies. Of those who remained in the study after 12 weeks, 55 percent who'd taken Serzone alone and 52 percent of those who'd gotten psychotherapy alone showed a response on a standard scale measuring depression.

Those who received the combined treatment showed an 85 percent response rate.

considered satisfactory. In this latter group, ``by no means are they all better,'' Keller said.

In the three treatment groups, about half the responders showed a remission.

Schulberg, the psychologist, said that to get results like those in the study, mental health providers would have to learn to do the special psychotherapy or otherwise make it available, monitor patient progress closely and alter the medication dose or course of psychotherapy accordingly.

Largest Study Ever To Compare Efficacy of Medication, Psychotherapy and The Combination of the Two in the Treatment of Chronic Depression

PRINCETON, N.J., May 18 /PRNewswire/ -- Bristol-Myers Squibb Company (NYSE: BMY) announced today that Martin Keller, M.D., chief study investigator and Mary E. Zucker, Professor and Chairman of the department of psychiatry and human behavior, Brown University School of Medicine, Providence, RI, presented new research findings from the acute phase of the landmark Serzone(R) (nefazodone HCl) Chronic Depression Study. The study demonstrates that combination therapy with Serzone and a form of psychotherapy developed for chronic depression is significantly more effective than either therapy alone. According to the study researchers, this combination therapy resulted in the highest rates of response and remission seen in any reported studies for chronic major depression. The findings were presented at the 1999 annual meeting of the American Psychiatric Association.

"As clinicians, we needed to know more about chronic depression. It's a condition that has been unrecognized for decades. It's only in the past few years that we have been able to separate chronic depression from an individual's character or personality, so that it is recognized as a treatable mental illness. We came to Bristol-Myers Squibb with our idea about this study. We thought the effectiveness and side effects profile of Serzone and our study design would be a good match," commented Dr. Keller.

The Serzone Chronic Depression Study represents the largest study of its kind ever undertaken comparing the efficacy of medication alone, psychotherapy alone and the combination of the two for the treatment of chronically depressed outpatients. This study evaluated Serzone and Cognitive Behavioral Analysis System of Psychotherapy (CBASP), either alone or in combination. CBASP is a psychotherapy designed specifically for the treatment of chronic depression (a major depression present longer than two years), and was developed by James P. McCullough, PhD, Virginia Commonwealth University. "When the researchers explained the study objectives, we believed it was extremely important to support this groundbreaking study on chronic depression," commented Rick Lane, president, U.S. Medicines Group, Bristol-Myers Squibb Company. "Our $20 million funding of this study further demonstrates Bristol-Myers Squibb's ongoing commitment to neurosciences research, and the development of effective and safe treatments for individuals suffering from depression and anxiety disorders."

More than 46 million Americans (ages 15-54) suffer from depression annually, and approximately one-third, or 14 million, of this group suffer from chronic depression. Recent reports indicate that depression costs the U.S. economy approximately $53 billion annually. The highest rates of depression occur among adults ages 25 to 44. Women are more likely to develop depression than are men.

The Global Burden of Disease Study (Murray GJ, Lopez, AD (1996)) identified depression as a leading cause of worldwide disability, ranking above heart attacks, strokes and diabetes. The factors contributing to the global level of disability associated with depression are high prevalence, increased rates of recurrence, chronicity, and associated medical and psychiatric comorbidity.

According to the study investigators, the next step is to translate the acute phase data into treatment guidelines for initial management of chronic depression.

Serzone is indicated for the treatment of depression, and is effective in reducing relapse. The most common side effects observed in clinical trials with Serzone included somnolence (sedation), dry mouth, nausea, dizziness, constipation, asthenia (weakness or debility), lightheadedness, blurred vision, confusion and abnormal vision.

Serzone is contraindicated in patients with known hypersensitivity to nefazodone or other phenylpiperazines. In addition, co-administration of terfenadine (Seldane(R)), astemizole (Hismanal(R)) and cisapride (Propulsid(R)) is contraindicated. Co-administration with monoamine oxidase inhibitors (MAOIs) is not recommended. Dosage reduction of triazolam (Halcion(R)) and alprazolam (Xanax(R)) are recommended when used with Serzone. Since any psychoactive drug may impair judgment, thinking or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Serzone therapy does not adversely affect their ability to engage in such activities.

This landmark clinical trial was conducted at leading academic institutions in the field of mental health research, including: Brown University, Providence, RI; New York Hospital-Cornell Medical Center, New York, NY; Emory University, Atlanta, GA; Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL; Stanford University School of Medicine, Stanford, CA; State University of New York at Stony Brook, NY; University of Arizona, Tucson, AZ; University of Pittsburgh, Pittsburgh, PA; University of Washington, Seattle, WA; University of Texas Medical Branch at Galveston, TX; University of Texas Southwestern Medical Center at Dallas, TX; and Virginia Commonwealth University, Richmond, VA.

Bristol-Myers Squibb Company is a diversified worldwide health and personal care company whose principal businesses are pharmaceuticals, consumer products, nutritionals and medical devises. It is a leading maker of innovative therapies for cardiovascular, metabolic and infectious diseases, central nervous system and dermatological disorders, and cancer. The company is also a leader in consumer medicines, orthopaedic devises, ostomy care, wound management, nutritional supplements, infant formulas, and hair and skin care products.

SOURCE Bristol-Myers Squibb Company