TUESDAY, Feb. 28, 2006 (HealthDay News) -- Many Americans have seen the television ad for Pfizer Inc.'s prescription antidepressant Zoloft.
It's the one with a listless ovoid creature moping about as a voice-over explains that depression may be due to a chemical imbalance in the brain, and that "Zoloft works to correct this imbalance."
Statements like these have been repeated so often in direct-to-consumer ad campaigns for selective serotonin reuptake inhibitor (SSRI) antidepressants that critics say they now have the ring of scientific truth.
That's why many Americans "might be particularly surprised that not a single article can be produced which directly demonstrates that depression is the result of a serotonin deficiency," said Jeffrey Lacasse, a doctoral student at Florida State University's College of Social Work.
Along with Jonathan Leo, an associate professor of anatomy at Lake Erie College of Osteopathic Medicine in Bradenton, Fla., Lacasse co-authored a recent article on the issue in the journal Public Library of Science Medicine. The two experts argued that ad claims by drug companies that depression is caused by a "serotonin imbalance" are unsubstantiated by the scientific literature, and could lead to an over-reliance on these drugs for the treatment of depression.
Leo and Lacasse said they wanted to make one thing clear: They do not dispute that SSRIs can help ease depression for some patients.
"We would never say that they don't help anybody -- there are many satisfied customers of SSRIs," Lacasse said.
However, the claim that the drugs work by redressing a serotonin imbalance in the brain is unfounded, he said.
"I came to this issue as I was investigating SSRIs for a preliminary exam, as part of my course work for my doctoral dissertation," Lacasse said. "As I was doing that, I noticed that the ads on television seemed to be contrary to the data I was reading in all my scholarly work."
A look at the current Diagnostic and Statistical Manual of Mental Disorders, the Bible of American psychiatry, lists the underlying cause of depression as "unknown," Lacasse said.
And there are other reasons to doubt the "serotonin imbalance" theory. First of all, it is currently impossible to measure levels of circulating serotonin (or any other neurochemical) in the living human brain. That means doctors and researchers have no means of determining what an appropriate "balance" of neurochemicals in the brain might be.
Leo and Lacasse also note that other interventions -- psychotherapy, exercise and non-SSRI drugs -- also help ease depression, even though "these other approaches have no known effect on serotonin," Lacasse pointed out. Studies have also tried to induce or alleviate depression in humans by artificially depleting or boosting serotonin levels -- to no effect, he said.
Finally, just because SSRIs can fight depression doesn't mean serotonin levels were the culprit in the first place, the researchers said.
"The fact that aspirin cures headache does not prove that headaches are due to low levels of aspirin in the brain," they noted, and the same may hold true for SSRIs and depression.
According to Lacasse and Leo, pharmaceutical companies do the public a disservice when they stress the serotonin imbalance theory in their ads.
"If you hear though that it's really nothing more than a 'chemical imbalance' -- that that's why you have these feelings -- it makes it all very simple and seductive," Lacasse said. And he believes that while millions of Americans turn to SSRIs in hopes of redressing that imbalance, other proven interventions, such as psychotherapy or exercise, are too often ignored.
Most experts agree that depression is a complex disease, probably originating in a combination of genetics, biochemistry and the emotional and social environment in which the patient lives.
Lacasse said he has reached out to the U.S. Food and Drug Administration, asking it to send drug companies "warning letters" aimed at changing the language they use in their advertisements. So far, he said, the only response has come from a former FDA regulatory reviewer, Lisa Stockbridge, who in her 2002 e-mail to Lacasse said drug ad statements regarding the cause of depression "are used in an attempt to describe the putative mechanisms of neurotransmitter action(s) to the fraction of the public that functions at no higher than a 6th grade reading level."
Attempts by HealthDay to reach the FDA for comment were unsuccessful.
Pfizer, the maker of Zoloft (generic name sertraline), defended the claims made in its ads. An Phan, a Pfizer public relations representative, said that "while a minority of physicians question whether SSRIs address a chemical imbalance in the brain, the role of these drugs in treating depression is well-accepted and documented."
Referring to two studies and excerpts from two psychiatric textbooks, Phan added that "there is considerable scientific literature supporting the widespread belief among scientists and physicians that an inadequate level of serotonin in the neuronal synapses of the brain is at least one of the causes of depression."
Another expert on SSRI medications said the truth on this issue may lie somewhere in the middle.
"While it's true that one could say that these drug companies are using a very oversimplified metaphor -- and a metaphor for something that may not even exist at all -- it's also wrong to suggest that it has no relationship to contemporary theories of mood regulation," said Dr. Peter D. Kramer, a professor of psychiatry and human behavior at Brown University, and the author of a seminal 1993 work on SSRIs called Listening to Prozac.
According to Kramer, there's no hard proof that serotonin imbalance causes depression, but he believes neurotransmitter dysregulation is certainly involved in the illness. "It does seem to be good for the brain to have some optimal handling of serotonin," he said. "On the other and, it's true that you just can't go into someone's brain and see an imbalance in serotonin, and say, 'This person is depressed.' "
Ideally, Kramer said, scientists, the media and the drug industry should let the public understand that depression is an exceedingly complex illness, without any single cause. On the other hand, the "serotonin imbalance" theory -- however flawed -- "may have served to de-stigmatize the condition and bring a different sort of patient into the [doctor's] office who formerly weren't even receptive to therapy," he said.
But Leo believes industry efforts to define depression as a chemical problem may be keeping people from the more comprehensive care they need.
"Instead of talking to a psychotherapist, or even a friend or religious person, or doing exercise or self-help, they identify it as a medical problem," he said. "And then there's the more general concern that less and less severely affected people will be taking these drugs as time goes on."
For more on depression, visit the National Institute of Mental Health.