Chronic depression: drugs show promise.

A majority of people who struggle through recurring periods of major depression for years, often returning to a low-grade sadness between episodes, improve markedly during 12 weeks of antidepressant drug treatment, according to early results from the largest-ever clinical trial aimed at relieving this debilitating condition.

"To get such a high response to weekly antidepressant administration with no psychotherapy was absolutely striking," asserts Martin keller, a psychiatrist at Brown University in Providence, R.I., and director of the ongoing multicenter study. "These people had been depressed for an average of 17 years."

Keller and his colleagues described their preliminary findings at the annual meeting of the American Psychological Association in Los Angeles last week.

About one in three cases of depression lasts more than 2 years and is classed as "chronic," Keller says. Some individuals suffer bouts of major depression that last for months or years at a time; some experience a persistent, moderate sadness known as dysthymia; and others encounter "double depression," in which at least 2 years of dysthymia lead to recurring major depression.

Chronic depression afflicts an estimated 3 percent to 5 percent of people in the United States at some time in their lives. However, scant research has examined either drug or psychotherapeutic treatments for this condition.

The new project, which began in April 1993, consists of 300 people with double depression and 240 with chronic major depression who sought help at one of 12 medical centers throughout the country. Two-thirds of each group took sertraline, a chemical cousin of Prozac (fluoxetine), for 12 weeks; the rest received imipramine, from another class of antidepressants, also for 12 weeks. Physicians adjusted the dose, if needed, on a weekly basis.

Another 16 weekly drug doses follow, after which clinicians administer antidepressants as needed for 76 weeks.

Volunteers who discontinue one antidepressant can switch to the other.

The data reported by Keller cover treatment for 89 individuals with chronic major depression and 123 with double depression. Most had attended college, yet about 30 percent had no job. A large majority were unmarried.

Approximately two-thirds of both depressed groups showed a significant lessening of their symptoms by the end of 12 weeks, Keller notes. The rest decided to stop receiving their assigned antidepressant, although most of these volunteers agreed to give the alternative drug a try.

A substantial minority of the entire sample had a history of anxiety disorders, such as panic attacks, in addition to chronic depression. Yet those with anxiety disorders responded as well to antidepressants as those without, holds Lorrin M. Koran, a psychiatrist at Stanford University Medical Center. In contrast, first-time major depression proves more difficult to treat with antidepressants when it is accompanied by anxiety problems, he says.

Participants with chronic major depression who expressed worries about physical health or cited physical symptoms, such as stomach problems and heart palpitations, were most likely to drop out of treatment, Koran notes.

Half the sample also received a diagnosis of personality disorder, adds Gabor Keitner of Brown University. Again, these individuals improved as much on antidepressants as those without personality disorders.

About 40 percent of volunteers had experienced the death of a parent or the divorce or separation of their parents during childhood, which may influence chronic depression, Keitner suggests.

Few participants had received adequate treatment with any antidepressant previously, says Michael Thase, a psychiatrist at the University of Pittsburgh. Past psychotherapy or drug treatment did not boost responses to antidepressants, he contends.