Persistence key to success in depression treatment

Washington -- New findings from a large study on effective ways to treat depression lend support to intuitive approaches employed in physicians' offices to help their many patients with the disorder. The key theme among the strategies: Don't give up.

The Sequenced Treatment Alternatives to Relieve Depression trial, known as the STAR*D trial, found that one in three depressed patients who had not achieved remission using an antidepressant became symptom-free with the addition of another medication. One in four did the same after switching to a different antidepressant.

The findings from the multicenter trial are believed to be the first to examine the effectiveness of depression treatments for people who did not become symptom-free after initial treatment with medication.

Depression affects more than 19 million Americans and is the leading cause of disability in the nation, according to new statistics released in February by the Depression and Bipolar Support Alliance, a national group based in Chicago. The lack of specialists, including psychiatrists, often leads patients to seek help from their primary care physicians.

The need to help physicians help their patients already has been recognized. Maine, for example, is leading one such effort, said Neil Korsen, MD, a family physician for 18 years and now medical director of the Depression in Primary Care Program for MaineHealth, a nonprofit health system in Portland.

"I think that [STAR*D] will add support to what we've been doing based more on common sense than on research findings," Dr. Korsen said. He said he often had talked with colleagues about the need to treat depression more aggressively and to consider increasing dosage or changing medications if one approach doesn't seem to be working.

The new trial provides guidance on what works, he said. "What's important to primary care physicians is that the intervention described is an intervention that we can do," he said. "We can try a second or third drug. We can safely try some combination treatments with two drugs."

Feeling like themselves

The findings also are significant because symptoms disappear rather than diminish, said Thomas Insel, MD, director of the National Institute of Mental Health, which funded the six-year, $35 million trial. "The goal was to find treatments that help people get well, not just better."

The trial included "real-world patients treated in real-world settings," said investigator John Rush, MD, professor of psychiatry at the University of Texas Southwestern Medical Center in Dallas. "This means that the results are applicable to the kinds of patients doctors see every day in psychiatric and primary care settings."

Relief was achieved in more than 50% of patients who initially had been resistant to treatment but were either switched to another medication or took a second drug in addition to the first, said Dr. Rush, who led the "switch" arm of the trial.

On the flip side, of course, nearly half of the patients were not helped. But since the trial is still under way with two more treatment levels being studied, improvements still could be seen, the researchers said.

The specifics

The switch arm examined outcomes for adult patients who, having failed to achieve remission of symptoms when taking the antidepressant citalopram, or Celexa, were switched to one of three other antidepressants: sustained-release bupropion, or Wellbutrin SR; sertraline, or Zoloft; or extended-release venlafaxine, or Effexor XR. The three alternatives were found to be equally effective.

In the augmentation arm, patients who failed to achieve remission after taking citalopram for three months were prescribed, in addition, either sustained-release bupropion or the anti-anxiety medication buspirone.

"If the first treatment attempt fails, patients should not give up," Dr. Insel said. "By remaining in treatment and working closely with clinicians to tailor the most appropriate next steps, many patients may find the best single or combination treatment that will enable them to become symptom-free."

Results from both trial arms were published in the March 23 New England Journal of Medicine.

Most physicians should be comfortable prescribing the medications used in the trial, as all are frequently used in primary care practice, Dr. Korsen said. Additional medication combinations also might be effective, and the MaineHealth program is exploring other options with psychiatrists and expects to include them in guidelines that will be posted on its Web site .

The STAR*D trial also employed the 17-item Hamilton Rating Scale for Depression to measure patients' progress, and physicians in the trial provided close follow-up care -- an important consideration for success, the researchers said.

Another, shorter measurement tool, the Patient Health Questionnaire, or PHQ9, is also recommended to help chart treatment progress, Dr. Korsen said. That measure has been validated and is available on several Web sites, including the site for MaineHealth. "Although the score doesn't tell the whole story, it gives you a sense of the symptom level over the last couple of weeks," Dr. Korsen said.

Helping to enhance the care provided to depressed patients in primary care settings is also the mission of the MacArthur Initiative on Depression and Primary Care, which is based at Dartmouth College in New Hampshire and Duke Medical Center in Durham, N.C. The initiative, which offers the PHQ9 on its Web site, is also developing practice systems, educational programs and methods to disseminate the ideas and materials to physicians nationwide.