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

Who Are We? Coming of Age on Antidepressants

By RICHARD A. FRIEDMAN, M.D.
Published: April 15, 2008

"I've grown up on medication," my patient
Julie 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 funda-
mental 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.

Julie 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 hadn't grown up before gettin' 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 pre-
scribed 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 Julie, 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 treat-
ment is small. A 2004 review by the FDA,
analyzing clinical trials of the drugs, did show
an elevated risk of suicidal thinking and non-
lethal 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 random-
ized 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 man-
dating 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 understand-
ably 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.
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