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Jim Rosack

The standard four to six months of antidepressant treatment after a major depressive episode is not enough, according to a new analysis of 31 clinical trials.

Long-term antidepressant use can significantly reduce a patient’s odds of recurrence or relapse of the depression, according to a new report.

Indeed, the report suggests, a year or two of medication therapy, rather than the more common four to six months, should be just what the doctor orders.

The report, from John Geddes, M.D., a professor of psychiatry at the University of Oxford, appeared in the February 22 issue of the Lancet.

The U.S. Agency for Health Care Policy and Research’s Depression Guideline Panel recommends a standard course of antidepressant medication for at least four to six months following the acute phase of a major depressive episode. The APA practice guideline on depression is more cautious, noting that "the optimal length of maintenance treatment is not known and may also vary depending on the frequency and severity of recurrences, tolerability of treatments, and patient preferences."

Geddes and his colleagues agreed with the APA guideline’s caution, saying that the standard four to six months is simply not sufficient.

30 Years of Data Studied

Geddes, along with a multinational group of co-authors, pooled data from 31 studies with continuation phases of antidepressant treatment ranging from six months to three years. Those 31 trials, published from 1973 to August 2000, all pointed in the same direction.

Of the collective 4,410 patients in the studies, those who continued antidepressant treatment for longer than one year had only one-third the odds of relapse of those who stopped taking antidepressants after six months. That reduction in odds resulted in less than half the number of patients experiencing recurrences or relapse if they continued taking medication.

"I think the first thing is," noted co-author David Kupfer, M.D., professor and chair of psychiatry at the University of Pittsburgh, "we have been arguing for some time that a long-term treatment approach to antidepressants makes a tremendous amount of sense. The long-term studies here certainly support that."

The common thinking used to be that if antidepressant medication was withdrawn from a patient who had taken it for a year, there would be a certain risk of relapse or recurrence. "And, if you treated that patient for two years, we wondered," Kupfer asked, "would that risk really go down?"

Kupfer said the new analysis seems to indicate that "it looks like whenever you withdraw patients from medications, the risk is still the same," at least across this large study sample.

"Once patients have had, let’s say, three episodes of depression, I would treat them as if they have diabetes and need insulin," Kupfer said. "That is, their depression is a chronic, life-long disorder." That is a shift in the clinical paradigm, he pointed out.

Kupfer noted that the review looked at 31 studies that deal only with antidepressant treatment.

"What I don’t know," he added, "is if I used a targeted psychotherapy, for example, just like a targeted pharmacotherapy—let’s say interpersonal or cognitive-behavioral therapy—and I continued using it with a patient for the long term, would I end up with the same results?

"The mantra I use, and it really hasn’t changed in the last 10 to 15 years," Kupfer said, "is that the treatment that got the patient better will keep the patient better. It’s that straightforward."

Treat to Recovery

Kupfer said clinicians need to drastically change their goal when treating depression.

"This is something still very high on my bully pulpit," he told Psychiatric News. "We need to treat people to complete recovery," not simply until their symptoms improve in response to the medication.

Unfortunately, he added, all the treatment trials used by the Food and Drug Administration to license antidepressants have been response trials, with no real measurement of recovery or even remission.

"We forget, as clinicians," he said, "that somebody who has an incomplete recovery has a risk of relapsing or having a recurrence that is much, much greater" than someone who recovers fully.

That fact is largely lost on primary care physicians, he added. Primary care tends to focus on the alleviation of the common somatic symptoms that are the reason the patient was seen originally, he said.

"And those somatic symptoms may get better, except for one or two. The patients are told they are better. Yet they still have all kinds of trouble doing the things they do as efficiently as they did before they became depressed, and their family life is still in shambles, and their spouse still wants a divorce because they are so hard to get along with. But the doctor says, ‘OK, you’re better. Goodbye.’ "

A patient, Kupfer emphasized, may be walking around with only a small number of vague symptoms, but a high level of dysfunction. "The whole notion," he added, "of subsyndromal symptoms is probably more significant, not before the major depressive episode, but after the episode."

He hopes the Lancet paper emphasizes that depression is often a serious and chronic medical disease. He noted that there are cases in which a patient has suffered some type of insult—loss of a job, death of a loved-one, divorce—and is appropriately depressed. Often those patients recover on their own. However, for those who have endured multiple episodes of depression, "this really should be treated like a chronic disease, just like we treat diabetes, heart disease, hypertension," Kupfer said.

"And the data here are very strong—it is as good as for any chronic medical disease," he concluded. "Long-term treatment works, and people who are treated with medication stay better—except when you take them off that medication."

A summary of "Relapse Prevention With Antidepressant Drug Treatment in Depressive Disorders: A Systematic Review" is posted on the Web at www.thelancet.com/journal/vol361/iss9358/abs/llan.361.9358.original_research.24671.1.


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