Should teenagers take drugs?

Health and medicine explained.
June 4 2004 4:30 PM

Should Teenagers Take Drugs?

Prozac, Paxil, and teen depression.

A pharmaceutical fix?
A pharmaceutical fix?

This week brought big news in the mood disorder business. First, the New York Times previewed a study, sponsored by the National Institute of Mental Health, that found Prozac to be remarkably effective in treating adolescent depression. Then New York Attorney General Eliot Spitzer announced that he had filed suit against GlaxoSmithKline, the pharmaceuticals giant. The charge is that the company manipulated or suppressed research data, to make its drug Paxil appear safe and effective in treating depression in children and teenagers, when it is neither.

Which are we to believe? Should doctors prescribe medication for depressed adolescents or hold off?

One answer is that we just don't know—precisely because drug companies manage the information about antidepressants, promulgating positive studies and suppressing evidence of harm or failure. For this reason, the Spitzer lawsuit is a very good thing. It promises to lead, if not through legislation then through the self-protective instincts of corporations, to greater openness about research results. The indictment is a damning document. It suggests that in the drug company's own research, Paxil looked ineffectual in children and adolescents. By releasing results of a single study that showed positive outcomes, GlaxoSmithKline was—this is the gist of the charge—misleading doctors and their patients.

It may just be that Prozac is more effective than Paxil in young patients. But it is also possible that the difference in the research results has less to do with the medication than with the nature of the studies. It turns out that drug companies are shockingly inept at testing their own products.

When independent psychiatrists and psychologists look at data submitted to the Food and Drug Administration—the results of corporations' early studies on their own antidepressants—the medications look only modestly effective. But these findings always strike me as suspect, since the same antidepressants have proven highly useful in treating recalcitrant kinds of depression, such as depression after strokes and post-partum depression. Why would the medications fail only in research on the run-of-the-mill mood disorders?

There are a number of answers to this puzzling question, but mostly it comes down to this: The pharmaceutical companies do shoddy research on the drugs' efficacy. Because the patents on medication have a limited duration, the corporations are always in a rush to bring drugs to market. The companies pressure the subcontractors that perform the studies, demanding that they gather research subjects fast. The recruiters then stretch diagnostic criteria, signing up patients who may not have the disease in question. Studies often include people with a host of shifting complaints, many of which are based less on acute illness than on personality style. The result is a group with poorly defined conditions and high placebo response rates—enough static to drown out whatever effects the medications have on substantial disease.

Drug company studies can have other problems. Sometimes they are conducted before the proper dosage or length of treatment has been established. Inexact dosing leads to low rates of response, or to excessive side effects—and a tendency for subjects to drop out of a study. These and other study design defects tend to make medications appear less effective than they prove in clinical practice or in later research.

In studies of younger patients, these problems are magnified. There is a sense in which all depressed children are "outliers." Whatever it is that causes depression—predisposing genes, stressful environment—you need large doses of it to contract mood disorder early in life. Children's symptom clusters are not always the same as adults'. Children are less able to report on their experience. Their brains develop at different rates. And they are hard to recruit into studies, because parents are often rightly concerned about their participating. So when you test drugs in children, you tend to be addressing small groups that on the relevant variables—brain biology, level of illness, diagnosis—contain heterogeneous members. Some research subjects will have disease based on severe physical pathology; some will simply be misdiagnosed. And no one imagines that antidepressants work in a high percentage of children. Researchers are listening for quiet signals in a system with loud background noise.

Oddly, then, in the "rush to market," drug company studies tend to hide the efficacy of the very medications that the corporations hope to promote. It is the rule, not the exception, for similar medications to fare poorly in drug company trials but to fare well in subsequent (presumably disinterested) government-sponsored research. The NIMH-supervised research on adolescent depression has not been published, which means that it has not undergone its final peer review. But it is known to be well-designed and carefully executed. It is likely to pass with flying colors and emerge, more or less as the Times reported, in the Journal of the American Medical Association. The study's results suggest that antidepressants are highly effective.

The NIMH study compares cognitive psychotherapy and Prozac, alone and in combination, to each other and to placebo. The subjects, 439 teens aged 12 to 17, had moderate to severe depression—a level at which diagnosis tends to be reliable. In the group that took Prozac, the Times reported, 61 percent showed some improvement, compared to 35 percent in the placebo group. Cognitive therapy helped 43 percent but overall was statistically hard to distinguish from placebo. Drug and talk therapies in combination helped 71 percent of subjects.

In the previous literature, almost nothing worked reliably for depression in adolescents. Here, the results for Prozac match or even exceed those seen in the treatment of adults. The fly in the ointment is the tendency toward suicide. The Times reported five suicide attempts among the subjects on Prozac, compared to just one among subjects on no medication—despite an overall decrease in the suicide attempt rate among all the subjects in treatment. In particular, psychotherapy seemed to mitigate the risk of suicide attempts in the drug treatment group.

How any of this news will affect clinical practice is unclear. The use of antidepressants in the young has always been a matter of "hard cases make bad law"; even in the absence of encouraging data, there are good reasons why doctors and parents have favored trials of medication treatment for adolescents with depression. Adolescents with early-onset depression fall behind their peers socially and developmentally. Some, like street kids treated in urban clinics, can ill afford any additional vulnerability.  And occasionally, the disease does respond dramatically to medication.

If the NIMH data stand up, they may lead to yet more aggressive prescribing. And although psychotherapy has not shown great effectiveness against teen depression in recent studies, the fear of medication-induced suicide may help to keep therapy in the mix—a sad reason for what might be a very good result. (I would hate to see a treatment for an adolescent that does not include the offer of counseling.) Still, it increasingly seems that medication use is critical in the treatment of severe depression.

If medications, on some fronts at least, are looking better, the drug companies are looking ever worse. Thoughtful doctors now discount positive outcome studies funded by corporate money, because they suspect that comparable negative studies may have been suppressed. Information control is a game of diminishing returns.

In a well-regulated society, all pre-marketing research on patients would be made public as a drug moves toward approval. Post-marketing follow-up would be taken out of corporate hands entirely. Years ago, I proposed that pharmaceutical houses be assessed a fee based on the sales of a new drug. That money would be put to use by the Food and Drug Administration or National Institutes of Health or a comparable agency, to fund studies of emerging side effects and of uses in under-researched populations, such as children.

Drug companies might well come to favor such proposals, as a means of shedding liability. Besides, it is not clear that painstaking studies by neutral parties would judge the medications to be less useful or more dangerous. So far, in fact, the better research has tended to find stronger drug effects. The approach that pharmaceutical houses have taken—controlling research, and then (allegedly) manipulating the flow of information—looks venal. In terms of their own interests, it may also be foolish.

TODAY IN SLATE

Politics

Blacks Don’t Have a Corporal Punishment Problem

Americans do. But when blacks exhibit the same behaviors as others, it becomes part of a greater black pathology. 

I Bought the Huge iPhone. I’m Already Thinking of Returning It.

Scotland Is Just the Beginning. Expect More Political Earthquakes in Europe.

Lifetime Didn’t Think the Steubenville Rape Case Was Dramatic Enough

So they added a little self-immolation.

Two Damn Good, Very Different Movies About Soldiers Returning From War

Medical Examiner

The Most Terrifying Thing About Ebola 

The disease threatens humanity by preying on humanity.

Students Aren’t Going to College Football Games as Much Anymore, and Schools Are Getting Worried

The Good Wife Is Cynical, Thrilling, and Grown-Up. It’s Also TV’s Best Drama.

  News & Politics
Weigel
Sept. 20 2014 11:13 AM -30-
  Business
Business Insider
Sept. 20 2014 6:30 AM The Man Making Bill Gates Richer
  Life
Quora
Sept. 20 2014 7:27 AM How Do Plants Grow Aboard the International Space Station?
  Double X
The XX Factor
Sept. 19 2014 4:58 PM Steubenville Gets the Lifetime Treatment (And a Cheerleader Erupts Into Flames)
  Slate Plus
Slate Picks
Sept. 19 2014 12:00 PM What Happened at Slate This Week? The Slatest editor tells us to read well-informed skepticism, media criticism, and more.
  Arts
Brow Beat
Sept. 20 2014 3:21 PM “The More You Know (About Black People)” Uses Very Funny PSAs to Condemn Black Stereotypes
  Technology
Future Tense
Sept. 19 2014 6:31 PM The One Big Problem With the Enormous New iPhone
  Health & Science
Bad Astronomy
Sept. 20 2014 7:00 AM The Shaggy Sun
  Sports
Sports Nut
Sept. 18 2014 11:42 AM Grandmaster Clash One of the most amazing feats in chess history just happened, and no one noticed.