Nov. 7, 2005 — Do the most widely prescribed antidepressants work by correcting a chemical imbalance in the brain? That’s being challenged in a newly published essay.

The essay’s authors say the assertion that depression results from an imbalance in the brain chemical serotonin and related chemicals is not supported by the scientific evidence.

They write that there is “a growing body of medical literature casting doubt” on the so-called “serotonin hypothesis.” But a widely known antidepressant researcher who spoke to WebMD disagrees.

Brown University psychiatry professor Peter D. Kramer, MD, is the author of Listening to Prozac and Against Depression.

“The connection between what these drugs do and what seems to be useful in the treatment of mood disorders is just as strong or stronger today as it was 13 years ago when I wrote Listening to Prozac,” he says.

Kramer acknowledges that there is still much to be learned about the impact of brain chemistry on depression and other mental illnesses. He says it is unlikely that serotonin imbalance alone explains depression, but he adds that Prozac and other antidepressants that target serotonin clearly help many people.

Are Ads Misleading?

Selective serotonin reuptake inhibitors (SSRIs), include the drugs Prozac, Paxil, Zoloft, Lexapro, and Celexa. The drugs increase the availability of serotonin, which acts as a chemical messenger in the brain among other areas.

Millions of Americans take SSRIs for depression and other mood disorders, and in the U.S. alone sales of the drugs top $10 billion a year.

In a newly published essay, anatomy professor Jonathan Leo, PhD, along with colleague Jeffrey Lacasse, say that SSRI ads aimed at the public are often misleading.

Leo teaches neuroanatomy at Lake Erie College of Osteopathic Medicine in Bradenton, Fla.

“The advertising is not portraying the science in a true light,” Leo tells WebMD.

He says the ads typically claim that SSRIs restore the serotonin balance of the brain but adds that there is “no such thing as a scientifically established correct balance of serotonin.”

Leo cites a 2002 review which found that SSRIs were only slightly more effective than placebo for treating depression. He adds that efforts to use brain imaging to document chemical imbalances linked to mental illness have proven disappointing.

He also points to studies suggesting that nondrug treatments, including psychotherapy and exercise, may be as effective as drugs for treating certain mental illnesses.

“As long as people are told about all these things I have no problem with using these drugs,” he says. “Without a doubt, they help some people. Our point is that the explanation for why they work is simplistic and potentially misleading.”

Movie Star Spat

Leo and Lacasse published their essay in the December issue of the Public Library of Science journal PLoS Medicine. The Public Library of Science is a privately funded, nonprofit group that publishes scientific and medical research and makes it freely available on its web site.

Leo says he hopes the paper will make the public aware that there is legitimate scientific debate about whether depression is caused by chemical imbalance.

“Professionals have researched and debated this issue for years. It is not just a public spat between two movie stars,” he says.

He is referring to actor Tom Cruise’s highly publicized criticism of actress Brooke Shields, who wrote earlier this year that SSRIs helped her recover from postpartum depression after the birth of her first child.

In a June appearance on NBC’s Today Show, Cruise called antidepressants “very dangerous” and claimed there was no proof that chemical imbalances in the brain drive depression.

Shields responded in a New York Times op-ed piece, calling Cruise’s assertions a “ridiculous rant.”

Kramer tells WebMD that while the serotonin hypothesis may not tell the whole story, it has led to the development of an important treatment for depression and other mental disorders.

“It turns out that the medicines that affect serotonin do other things, such as protect the nerve cells and enhance [the generation of new nerve cells],” he says.