Who Are We? Coming of Age on Antidepressants

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April 15, 2008

Who Are We? Coming of Age on Antidepressants

By RICHARD A. FRIEDMAN, M.D.

http://www.nytimes.com/2008/04/15/health/15mind.html

" I've grown up on medication, " my patient told me recently. " I

don't have a sense of who I really am without it. "

At 31, she had been on one antidepressant or another nearly continuously

since she was 14. There was little question that she had very serious

depression and had survived several suicide attempts. In fact, she

credited the medication with saving her life.

But now she was raising an equally fundamental question: how the drugs

might have affected her psychological development and core identity.

It was not an issue I had seriously considered before. Most of my

patients, who are adults, developed their psychiatric problems after

they had a pretty clear idea of who they were as individuals. During

treatment, most of them could tell me whether they were back to their

normal baseline.

could certainly remember what depression felt like, but she could

not recall feeling well except during her long treatment with

antidepressant medications. And since she had not grown up before

getting depressed, she could not gauge the hypothetical effects of

antidepressants on her emotional and psychological development.

Her experience is far from unique. Since their emergence in the late

1980s, serotonin reuptake inhibitors like Prozac and Zoloft have become

some of the most widely prescribed drugs in the world, for depressed

teenagers as well as adults. Because depression is often a chronic,

recurring illness, there are certain to be many young people, like

, who are coming of age on these newer antidepressants.

We know a lot about the course of untreated depression, probably more

than we do about very long-term antidepressant use in this population.

We know, for example, that depression in young people is a very serious

problem; suicide is the third-leading cause of death in adolescents, not

to mention the untold suffering and impaired functioning this disease

exacts.

By contrast, the risk of antidepressant treatment is small. A 2004

review by the Food and Drug Administration, analyzing clinical trials of

the drugs, did show an elevated risk of suicidal thinking and nonlethal

suicide attempts in young people taking antidepressants --- 3.5 percent,

compared with 1.7 percent of those taking a placebo. But since the

lifetime risk of actual suicide in depressed people ranges from 2.2 to

12 percent, risk from treatment is dwarfed by the risks of the disease

itself.

Still, what do we know about the effects of, say, 15 to 20 years of

antidepressant drug treatment that begins in adolescence or childhood?

Not enough.

The reason has to do with the way drugs are tested and approved. To get

F.D.A. approval, a drug has to beat a placebo in two randomized clinical

trials that typically involve a few hundred subjects who are treated for

relatively short periods, usually 4 to 12 weeks.

So drugs are approved based on short-term studies for what turns out to

be long-term --- often lifelong --- use in the world of clinical

practice. The longest maintenance study to date of one of the newer

antidepressants, Effexor, lasted only two years and showed the drug to

be superior to a placebo in preventing relapses of depression.

What do I say to a depressed patient who is doing well after five years

on such a drug but can't stop without a depressive relapse and who wants

reassurance that the drug has no long-term adverse effects?

I usually say that we have no evidence that the drug poses a risk with

long-term use; and since the risk of untreated depression is much

greater than the hypothetical risk of the drug, it makes sense to stay

on it.

This large gap in our clinical knowledge is compounded by the public's

growing and well-founded skepticism about research sponsored by drug

makers. A study in the January 2008 issue of The New England Journal of

Medicine, involving 74 clinical trials with 12 antidepressants, found

that 97 percent of positive studies were published, versus 12 percent of

negative studies.

Clearly, physicians and the public need much better data on the safety

and efficacy of drugs after they hit the market, which at present

consists mainly of anecdotes and case reports.

Congress recently reauthorized the Prescription Drug User Fee Act, which

will expand the F.D.A.'s post-marketing drug surveillance, though I

think it did not go far enough in mandating the use of powerful

epidemiological strategies to monitor drugs over the long term.

Beyond these concerns, there are other important issues to consider in

long-term use of antidepressants, especially in young people. One

patient, a woman in her mid-20s, told me that she felt pressured by her

boyfriend to have sex more often than she wanted. " I've always had a low

sex drive, " she said.

For the past eight years she had been taking Zoloft, which like all the

antidepressants in its class is known to lower libido and to interfere

with sexual performance. She had understandably mistaken the side effect

of the drug for her " normal " sexual desire and was shocked when I

explained it: " And I thought it was just me! "

This just underscores how tricky it can be to use psychotropic drugs

during adolescence --- when the brain is still developing, when one's

identity is still work in progress.

The drugs save lives, and we often have no choice but to use them ---

even if we have questions about their long-term use. But the questions

are big ones, and we owe it to our patients to try to answer them.

A. Friedman is a professor of psychiatry at Weill Cornell

Medical College.

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