Mood meds' second wind: depression drugs aided by extra treatment step.

A second, modified course of drug treatment fosters recovery in a substantial minority of depressed adults who don't feel better after treatment with a commonly prescribed antidepressant, according to a federally funded investigation.

Among depressed patients who didn't improve on the antidepressant citalopram (Celexa), one in four became virtually symptomfree by switching from citalopram to a second antidepressant. In another test, one in three patients improved comparably within 14 weeks of adding another antidepressant to their citalopram regimen.

The researchers had earlier reported that about a third of patients get relief from citalopram alone. With the effect of the supplemental drugs, about half of the 4,041 depressed patients participating in the project shed most or all of their symptoms.

"A 50 percent remission rate is extraordinarily good given major depression's chronic nature," says psychiatrist A. John Rush of the University of Texas Southwestern Medical Center at Dallas, director of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

The researchers studied outpatients with major depression at 41 U.S. psychiatric and primary care facilities. Participants initially received citalopram for an average of 47 days. The drug increases serotonin activity in the brain. About 30 percent of people displayed symptom remission, Rush's group reports in the January American Journal of Psychiatry. Results for still-depressed patients who chose a second treatment appear in two reports in the March 23 New England Journal of Medicine.

A team led by Rush studied 727 patients who switched medications. Each volunteer was randomly assigned to receive either sertraline, another serotonin-enhancing drug; bupropion, a dopamine-and-norepinephrine booster; or venlafaxine, which raises availability of serotonin and norepinephrine to brain cells. Each medication yielded remission in 25 percent of patients.

A group led by University of Texas psychiatrist Madhukar H. Trivedi studied 565 patients who continued taking citalopram along with either bupropion or the serotonin-enhancing drug buspirone. In each group, 33 percent of the patients became symptomfree.

Another 369 patients opted for a form of psychotherapy called cognitive therapy, either alone or with medications. The results of those treatments will be published later this year. In other studies, cognitive therapy has worked as well as antidepressants as a primary treatment (SN: 11/5/05, p. 299).

Certain genetic traits may identify individuals likely to benefit from specific antidepressants, Trivedi says. A genetic analysis of 1,953 STAR*D patients, slated to appear in the May American Journal of Human Genetics, shows that many people who responded well to the initial treatment with citalopram possess a specific version of a gene critical to serotonin transmission.

The new findings are "illuminating and disconcerting," says psychiatrist David R. Rubinow of the University of North Carolina at Chapel Hill. Half of the participants stayed depressed, he notes.

It's puzzling that medications with different chemical effects create the same improvement, he adds, noting that the study lacked a group that received placebo pills.

STAR*D results apply only to individuals willing to take antidepressants in the first place and who can tolerate their side effects, comments psychologist David Antonuccio of the University of Nevada School of Medicine in Reno. The antidepressants' many side effects led about 20 percent of the STAR*D patients to discontinue treatment.