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Mysteries of the Mind

We're in the Dark About the Drugs We Use

By Shannon Brownlee
Sunday, October 3, 2004; Page B01

For anyone sitting in a nondescript ballroom at the Bethesda Holiday Inn last month, the testimony from families whose children had killed themselves -- by hanging, by knife wound -- while taking antidepressants was heartbreaking. For the families, however, the subsequent decision by the Food and Drug Administration panel that heard their stories -- to require a suicide warning on the antidepressants' labels -- was a vindication. And a long-awaited one at that. Several of the family members who testified have been arguing for more than 13 years that the drugs can trigger devastating side effects.

Still, many of those who have been involved in the effort to get the word out are undoubtedly wondering why it took so long. Psychiatric researchers first reported that the antidepressants known as SSRIs could spark suicidal thoughts and actions in young patients back in 1990, just three years after the first major SSRI, Prozac, hit the market. Since then, there have been thousands of scientific papers published on these medications. You'd think the psychiatric research community would have noticed that the drugs can be dangerous for some patients -- particularly kids -- and may not be terribly effective for most.

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The fact is, many academic psychiatrists did notice, and some spoke up, but practically nobody listened. "There has been a collective decision to ignore the evidence," says Jane Garland, head of pediatric psychiatry at the University of British Columbia Children's Hospital in Vancouver. "Our clinical practice guidelines say these things are safe and effective. The published papers say these drugs are effective and well tolerated. But the argument is very weak when you really look at the data."

That collective decision has its roots in the problem that has beset psychiatry since the days of Sigmund Freud: Understanding the mind is really hard to do. It's not as if physicians can administer a blood test to determine if a patient is depressed or anxious or obsessive-compulsive. Rather, psychiatry defines -- and diagnoses -- psychiatric disorders on the basis of subjective symptoms that are reported by patients or observed by doctors.

As a result, what gets counted as significant mental illness versus, say, unusual behavior or a minor disability has tended to expand and contract with changing social mores. Homosexuality was classified as a mental illness one year and a lifestyle choice the next, while severe shyness has now been elevated to a disease known as social anxiety disorder. Meanwhile, what's actually going on inside a patient's brain remains a cipher.

The diagnosis of mental illness has also been dictated in part by whatever is available to treat it. The psychiatric community has a long history of falling in and out of love with a succession of drugs that have been touted by the drug industry for whatever mental disorder is in vogue at the moment. In the 1960s, the vast majority of symptoms were interpreted as signs of anxiety disorders, and tranquilizers such as Valium were seen as the antidote for patients who weren't sick enough to be hospitalized. By the 1980s, the diagnosis du jour was depression, and the tranquilizers gave way to antidepressants such as Elavil and Nardil.

Unfortunately, this earlier class of antidepressants had their own problems. Nardil and other drugs of the class known as monoamine oxidase inhibitors (MAOIs) could trigger dangerously high blood pressure, while the so-called tricyclic antidepressants such as Elavil could be used to commit suicide by overdose. Enter Prozac, which was touted by manufacturer Eli Lilly as being safe at any dose. Never mind that studies showed that Prozac and the other SSRIs that soon followed (Zoloft, Paxil, Serzone, Luvox, Effexor, Celexa and Lexapro) were no more effective than older antidepressants, and that patients stopped using them in droves because they didn't like the side effects; psychiatrists greeted the new drugs with open arms.

Bernard Carroll, a professor emeritus of psychiatry from Duke University recalls, "You never saw anything like the mass hysteria over the 'next generation' antidepressants." This enthusiasm was driven in part, he says, by thought leaders in academic psychiatry, who were "desperate to demonstrate that all the federal research dollars that had been shoveled their way for 25 years actually had a payoff."

But the new antidepressants were also appealing because they fit neatly into the nascent understanding of the role of neurotransmitters, or brain chemicals, in mental illness. According to the prevailing theory, depression and suicide were linked to low levels of the neurotransmitter serotonin. The SSRIs, which stands for selective serotonin reuptake inhibitors, were thought to restore the chemical to healthy levels in the brain.

The notion that depression is a biological ailment, like Alzheimer's, proved enormously appealing to patients. It relieved much of the stigma of mental illness, which could now be viewed not as a personal or moral failing, but as a glitch of biology. The serotonin theory also appealed to the medical community, for a slightly different reason. It made the mind seem more knowable, less like a black box, and psychiatry seem more like real science, instead of a lot of Freudian talk about repression and sex. Psychiatrists could now say to patients, you are sick because of a deficiency, and these drugs will restore you to normalcy and mental health.

If only psychiatric disease were that simple. In reality, there is little research to show that being a quart low on serotonin leads to depression, and even less to suggest that patients who commit suicide have lower levels of serotonin than normal people. And nobody really knows what SSRIs actually do in the human brain.

Yet the serotonin theory lives on in the public's mind, while many members of the psychiatric community seem so invested in the power of the SSRIs that they have lost touch with the fact that all psychiatric drugs can have powerful side effects. Many in the field have long insisted that it is the depression that makes patients commit suicide, never the drugs, despite evidence that at least in some cases, it is indeed the medication. Studies of healthy volunteers, for example, have shown that people with no history of mental illness can suddenly begin having suicidal thoughts after taking the drugs.

Meanwhile, some psychiatrists report increasing numbers of young patients with severe psychiatric symptoms, including anxiety and mania, which appeared after they began taking SSRIs. Yet rather than seeing those symptoms as possible side effects of the medication, many academics have interpreted them as signs of previously undiagnosed manic depression, or bipolar disorder. The SSRIs, in their view, are "unmasking" bipolar disorder, which was there all along.

But there are no studies that support the notion that an individual patient's "underlying" bipolar disorder would have emerged at some later date had he or she not taken the drug. It is equally plausible that the drugs themselves trigger bipolar disorder, rather than uncovering it -- just as LSD is known to alter the brain's wiring and cause flashbacks, and the street drug MPTP can trigger a Parkinson's-like disorder.

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