Mysteries of the Mind

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Mon, 4 Oct 2004 20:22:46 -0400

Mysteries of the Mind

 

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washingtonpost.com

 

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.

 

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.

 

None of which is meant to diminish the suffering caused by mental

illness, or to suggest that the SSRIs should be removed from the

market. The drugs can, in fact, work miracles, lifting some patients

from the depths of depression and releasing others from the grip of

compulsiveness and anxiety. Taking an SSRI has undoubtedly prevented

some patients from killing themselves, and even the drugs' most vocal

critics prescribe them, albeit with caution. " There is still a place

to use [the SSRIs], " says British psychiatrist David Healy, " but we

should use them with great care. "

 

That's probably what every physician should have been doing all along.

But after more than a decade of companies burying their negative

studies, of faulty biological theories, and of psychiatrists ignoring

the data, maybe it's time for everybody -- patients, parents, doctors

and pharmaceutical companies -- to pause for a moment and take stock.

 

Before the antidepressants came along, estimates put the rate of

depression at 50 to 100 people per million in the population. Today,

we are led to believe that 100,000 Americans per million suffer from

the disease. That's one in 10 people, a thousand-fold increase in

about 30 years. It's hard to imagine that we are plagued with that

much more mental illness than ever before.

 

What's more likely is that the field of psychiatry, with its shifting,

subjective diagnostic categories and its enthusiasm for new drugs, has

been acutely vulnerable to " disease mongering. " This is the

increasingly common practice on the part of the pharmaceutical

industry to broaden the perceived market for a drug by persuading

doctors and the public that huge numbers of people suffer from this or

that disorder. Between disease mongering and some doctors handing out

SSRIs like Pez, antidepressant prescriptions for children have surged

27 percent since the mid-1990s. Today, between 1 million and 3 million

kids under the age of 19 are on one or more of these drugs for

diagnoses ranging from attention deficit disorder to migraines to

schizophrenia. Taking SSRIs has become so commonplace that young

people talk casually about needing to " adjust their meds " in response

to a rough week at school or a bad breakup.

 

Meanwhile, doctors have been prescribing these medications without

knowing until just recently that, according to the FDA, 2 to 3 percent

of their young patients could be at risk for drug-induced suicidal

thoughts or actions. Maybe that's because academic psychiatry has been

too busy performing research with a very different agenda to answer

the fundamental questions. In their haste to partake of industry

research funds and other perks, academic researchers have focused much

of their effort on what Carroll calls " experimercials " -- studies

aimed at expanding the drugs' " off-label, " or unapproved, markets.

 

And so doctors still can't tell which patients are most likely to

benefit from taking an SSRI. Nor can they predict which ones are most

likely to suffer devastating reactions. They still don't have any idea

how, biochemically, the drugs might trigger suicide and bipolar

disorder. In his book " Let Them Eat Prozac, " psychiatrist Healy writes

that the story of the SSRIs " reveals a lack of research so complete

that academics cannot avoid questions about how well the health

science research community serves us. "

 

Aside from the patients who have suffered and died, the other tragedy

of the antidepressant era is that some of the brightest minds in

academic medicine have spent so much time and money on research that

has done so little to elucidate the three-pound universe inside our

skulls. Far from being the most studied drugs on the planet, the SSRIs

are simply the most heavily marketed, while the mind and its illnesses

remain as mysterious as the cosmos.

 

Author's e-mail:

 

brownlee

 

 

 

Shannon Brownlee is Bernard L. Schwartz Senior Fellow at the New

America Foundation. She is writing a book on the excesses of American

medicine.