Antidepressants: Are They Effective or Just a Placebo?

In practice, only about one-third of patients with depression will be helped by the first drug they try. Many people improve on their own or with talk therapy. About 8% to 14% patients will respond badly to medication, experiencing increased thoughts of suicide after taking it, a response that appears with equal frequency in placebo takers. So the question becomes not whether antidepressants work better than placebo, but how they will work, in whom and under what conditions.

This Is Your Brain on Drugs
Aimee Hunter, a research psychologist at the University of California, Los Angeles, has long studied individual responses to antidepressants. Being skeptical of the true effectiveness of the drugs, she says she was originally interested in researching the impact of placebos. But over the years, her own data began convincing her otherwise. "I've come to see now, by doing the research myself and spending hours looking at numbers, that the medication is absolutely doing something," Hunter says. (See a special report on how to fix your phobias.)

In their most recent paper, Hunter and her colleagues looked at the relatively rare but serious side effect of suicidal ideation during depression treatment. The goal of their study, published in April in the journal Acta Psychiatrica Scandinavica, was to use patterns of brain activity to identify the subgroup of patients who might be at risk — a finding that could help doctors steer patients toward the most beneficial medication early in treatment.

Using a technique called quantitative electroencephalography (QEEG), in which patients' brain activity is recorded through a cap of electrodes placed on the scalp (the data is then amassed and organized into a map of brain activity), Hunter studied 72 depressed patients. They were given one of two widely prescribed SSRIs — fluoxetine (Prozac) or venlafaxine (Effexor) — or placebo for eight weeks.

Each patient was brought in five times over the course of the study for QEEG measurements and mood questionnaires, starting 48 hours after taking the first pill. Previous work by Hunter had already pinpointed a specific region of the brain, the midline/right frontal (MRF) area, where activity diverged between patients taking antidepressants and those taking placebos. In the antidepressant group, MRF activity was found to drop, while increasing slightly in placebo takers. (See "The Year in Health 2009: From A to Z.")

In the new study, Hunter found a similar yet surprising effect: depressed patients who developed suicidal thoughts while taking an antidepressant had a decrease in MRF activity six times larger than that seen in the placebo group, just 48 hours after starting the drug. This pattern was not seen even in placebo-taking patients who had begun having suicidal thoughts. "It was really dramatic, and the magnitude of the change was really impressive," says Hunter.

The fact that the changes occurred after just two days makes the result potentially useful in clinical practice as well. If Hunter's finding holds up, it could mean that a noninvasive, relatively cheap test — QEEG machines are not prohibitively expensive as far as medical equipment goes — could be used to determine whether a patient is at risk for a potentially deadly side effect of treatment. And because such side effects typically appear long before the benefits kick in, this would give physicians an advantage in helping patients find the most effective medication as quickly as possible.

"It's an awfully interesting [study]," says David Healy, a psychiatrist and author of Let Them Eat Prozac, a critique of the $9.9 billion antidepressant industry. "It will be interesting to see how things pan out when more people try to replicate it."

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