The Report Card on Antidepressants

It is not unusual for a depressed patient of mine to come into my office sad and weepy, and leave after an hour feeling buoyed up. There is a sense of relief that comes from being with someone who understands and a sense of hope that comes from being with someone you feel has the power to make things better.

These are important aspects of what happens in psychotherapy, and they are also likely important aspects of the placebo effect. Patients who receive placebos are being seen by medical staff and are getting some of that relief and some of that hope.

Flipping Brain Switches

Sometimes people fail to realize that what medication does and what psychological factors do both have an impact on the brain. Dr. Helen Mayberg, now at Emory University, studies brain circuits in depression. She used a neuroimaging method to study metabolism across brain regions in patients who responded to Prozac and in those who responded to a placebo.

She found that among the placebo responders were a number of specific regions with metabolic increases and others with metabolic decreases. These same changes were also seen in the Prozac responders, suggesting that this is what the brain needs to do to feel better, regardless of how it gets there.

But that's not the whole story. Because there were also some changes unique to the Prozac responder brains, Mayberg and her colleagues speculate that these other changes might be important in maintaining longer-term response and preventing depression.

Indeed, to return to the PLoS study with which we started: It would be interesting to know what happened after the six weeks that most of the individual treatment studies lasted. Were the patients who responded to antidepressants more likely to stay well longer than those with a placebo response?

A recent study by Dr. Arif Khan and colleagues at the Northwest Clinical Research Center in Bellevue, Wash., addresses exactly this question. They analyzed eight antidepressant studies in which drug and placebo were continued in responders for at least four months. The result: Placebo responders were more likely to suffer a recurrence of depression than antidepressant responders.

And now for take-home message No. 2: There still might be some advantage to antidepressants even for mild and moderate depression.

Dr. James Potash is an associate professor of psychiatry and co-director of the Mood Disorders Program at the Johns Hopkins School of Medicine in Baltimore. If you have questions or comments, please e-mail at To participate in our genetic and clinical studies, call 877-MOODS-JH.

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