Teens, drugs, and sadness
August 30, 2004
By Nancy Shute, US News

Is a combo of pills and talking the best remedy for depression?

Walk into any high school classroom in the country today, and chances are at least one student there is suffering from a debilitating illness called depression. But when parents seek help for their children, they all too often find themselves frustrated by a lack of information on how best to treat the psychiatric disorder. Despite the high rate of depression in kids, remedies have for the most part been untested, so families of these kids have been left to grope in the dark.

Last week the darkness lifted a bit, when researchers made public the results of the first study to compare depression treatments in teenagers. The headline of their work: Nearly 3 in 4 of their young patients improved significantly with a combination of psychotherapy and Prozac, a popular brand of the antidepressant drug class known as SSRI s. Of the 439 teens who participated in the nationwide study, 61 percent of those receiving Prozac alone got better after 12 weeks of treatment.

Psychiatrists widely praised the findings as long-overdue and much-needed evidence in the confusing and increasingly controversial realm of depression treatment. The study is also an all-too-rare application of the controls that are standard in nonpsychiatric medical trials, in which participants are randomly assigned to different treatments and neither they nor their physicians know if they're getting the medication being tested or a dummy pill. "We now have solid clinical evidence that we can help kids significantly--and pretty quickly," says David Fassler, a child and adolescent psychiatrist in Burlington, Vt. "I think parents and physicians should be reassured."

Patient advocates also welcomed the findings. "It should take a lot of fear away from families," says Lydia Lewis, president of the Depression and Bipolar Support Alliance in Chicago. "The whole deal of patient empowerment is knowledge. You can't know if you're getting good treatment unless you know what good treatment is."

The teenagers who received the combination treatment got 15 sessions of cognitive-behavioral therapy, a widely used form of psychotherapy that focuses on recasting the negative thoughts typical of depression and increasing positive thoughts and actions. Sessions with parents and other family members were included. Previous studies have shown cognitive-behavioral therapy alone to be very effective in treating depression in adolescents, with about 60 percent showing improvement. But in this case, talk therapy alone helped just 43 percent of the time, a number not much different from the 35 percent who improved while taking placebo pills. John March, a child psychiatrist at Duke University Medical Center and lead researcher for the Treatment for Adolescents With Depression Study (known as TADS), whose results were published in last week's Journal of the American Medical Association, says the poor response to talk therapy may reflect the fact that the study included only patients with moderate to severe depression and that most study participants had been depressed for about a year.

The TADS research is also significant because it is one of the very few studies of antidepressants that were not financed by a drug manufacturer; instead, backing came from the National Institute of Mental Health. Antidepressants have come under increased scrutiny in the past year after it was revealed that pharmaceutical companies have failed to publish data suggesting increased rates of suicide in people taking SSRI antidepressants, the most commonly used form of the drugs. Teenagers and adults in their early 20s are far more likely to commit suicide than older adults. Each year, about 20 percent of adolescents contemplate suicide; by the end of high school, 1 in 10 of those has attempted suicide, with almost 2,000 succeeding each year. Half of those who die had major clinical depression, which is characterized by feelings of hopelessness, isolation, and irritability.

What's to blame?
Psychiatrists have long known that some people become agitated, anxious, and have trouble sleeping when they start taking SSRI s. The speculation is that this "activation" may make patients more apt to injure themselves or others, because the drug has lessened the despair and lassitude typical of depression. But there are no reliable data available to support this theory. And because suicide is an outcome of the condition that the drugs are supposed to treat, it's difficult to sort out whether the disease or the treatment is at fault.

Prozac (generic name fluoxetine), the drug used in the TADS study, is the only SSRI antidepressant approved by the Food and Drug Administration for use in children. But physicians frequently prescribe other SSRI s, which include Zoloft, Paxil, and Effexor, to children "off label," a practice allowed by the FDA. Thus, there is intense interest in finding out whether all SSRI s increase the risk of suicide or whether some may pose more of a risk than others.

Last year, the FDA's British counterpart, citing unpublished data, banned the use of SSRI s--aside from Prozac--for children. In March, the FDA ordered antidepressant manufacturers to add warning labels urging physicians to watch patients closely for worsening depression and suicidal tendencies. On September 13, the FDA will convene an advisory committee meeting to review a new analysis it ordered on suicide risk and antidepressants, and it is expected to announce further action then.

Last week's report doesn't answer the suicide question, because it followed too few participants over too short a time to detect trends. March's group is continuing the TADS study and is also launching a second study of SSRI use in 1,600 children that he hopes will provide some answers. But the TADS data do show that, while suicidal thoughts were reduced from 29 percent to 10 percent for all study participants, those taking Prozac were slightly more likely to harm themselves or others. Cognitive-behavioral therapy, both alone and with Prozac, appeared to have a protective effect. March and other psychiatrists say this points out the importance of carefully monitoring any patient given antidepressants, particularly in the first weeks. "Hopefully, this trial will do away with the idea that any kid who takes SSRI s will get psychotic mania and kill themselves," March says.

Indeed, although psychiatrists say more research on the safety of SSRI s is urgently needed, they also fear that the increased publicity on potential risks may frighten parents away from seeking help for their children. Untreated depression, they contend, is far more likely to result in suicide. Already, 80 percent of children with mental illness in the United States aren't getting any treatment, according to the surgeon general, and parents who do seek help for their children often find themselves thwarted by insurers who don't cover mental-health care and by a lack of qualified therapists. "It might take some moxie to get your kid to the head of the line, because mental-health care is pretty severely rationed in this country," says Ken Duckworth, a child psychiatrist and medical director for the National Alliance for the Mentally Ill. "But the biggest risk is to do nothing."

Depression: not for adults only
Just a few decades ago, doctors in training were taught that it was impossible for children to suffer from clinical depression. Now it's recognized that it is as common in teenagers as it is in adults. Depression is particularly worrisome in teens because it raises the risk of suicide, which is far more common in adolescents and young adults than in older adults.
[list]Teens with major depression: 5 percent
Depressed teens getting treatment: 1 in 5
Teens who attempt suicide each year: 500,000
Those who succeed: 2,000[/list:u]
Sources: Surgeon general's report on mental health, American Academy of Child and Adolescent Psychiatry