BioEd Online

Can depression be explained by a simple chemical imbalance in the brain? A pair of researchers has complained that the evidence for this is weak, and that drug companies should not be allowed to push this message in their advertisements.

After being bombarded by messages that depression is caused by the lack of a certain chemical in the brain, say the researchers, patients may be sceptical of other kinds of treatment, including other drugs and talking to a therapist.

"That message [in the advertisements] is at odds with what's in the scientific literature," says Jonathan Leo of the Lake Erie College of Osteopathic Medicine in Bradenton, Florida, who co-authors an essay on the subject in PLoS Medicine this week¹.

The duo would like the Food and Drug Administration (FDA), which regulates drug advertising in the United States, to take a look at antidepressant ads and issue warnings to any firm that does not comply with its rules.

Feeling better

At issue are a class of antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs). The class includes such blockbusters as Prozac (fluoxetine), Zoloft (sertraline) and Paxil (paroxetine).

These drugs block the reuptake of serotonin, a molecule that relays signals in the brain and that has an effect on mood. In clinical trials, these drugs have helped people with depression, although some fear that they increase suicide rates in depressed children (see ' Bitter Pills').

Leo says that the mechanism behind the action of these drugs is unclear. A deficiency of serotonin has never conclusively been shown to cause depression, he says. Attempts to induce depression by turning down serotonin have not worked, he notes. And other compounds that elevate serotonin do not always relieve depression.

Leo adds that some studies have shown that exercise, placebo pills, and non-serotonin-related drugs have all performed as well as or better than SSRIs in elevating mood.

"The effect of other antidepressants seems to be as good," agrees Irving Kirsch of the University of Plymouth, UK. He says that further research is needed to demonstrate that people suffering from depression have problems with brain serotonin levels. And, he adds, more research is needed to show that the effect of SSRIs is really greater than the placebo.

"How SSRIs relate to the therapeutic benefits is still obscure," agrees Robert Findling of Case Western Reserve University in Cleveland, Ohio, who has consulted drug manufacturers on the topic. But, he stresses, "there is strong evidence that SSRIs do alleviate major depression."

Finding the balance

Leo and Jeffrey Lacasse of Florida State University in Tallahassee sought out and analysed advertisements to see if they conveyed these uncertainties about SSRIs.

One previous decision in a similar situation led them to think that the FDA might be interested in their findings: in 2002, the Irish Medicines Board, the regulatory equivalent of the FDA in Ireland, banned a major drug company from claiming in their patient information leaflets that paroxetine corrected a chemical imbalance.

Many of the ads the two researchers looked at do mention the general uncertainty about the causes of depression, and say only that a serotonin drop "may" be responsible. But Leo and Lacasse point out that FDA regulations require ads to disclose the "limitations of the supporting evidence" for such claims.

The duo hope that the FDA will take a look at these ads. "I'm not sure that would solve the problem but at the very least warning letters would help," says Lacasse.

Changing the advertisements, Leo hopes, will stop people thinking that depression is all down to a simple see-saw of chemicals in the brain, and might open their eyes to other solutions.