Antidepressants Potentially Misused in Treating Adolescents, Stanford Study Finds.

STANFORD, Calif. -- When the U.S. Food and Drug Administration declared in 2004 that certain antidepressants are linked to an increased risk of suicide in adolescents, there was surprisingly little data about how depression was being treated in young patients. Now new research from the Stanford University School of Medicine provides critical documentation of the potential misuse of these medications in the years leading up to the FDA's decision to issue the so-called "black-box" warnings.

The researchers found that, despite clinical guidelines calling for depressed adolescents to be treated with a combination of psychotherapy and medication, antidepressants began supplanting--rather than complementing--the role of mental health counseling between 1995 and 2002. And although only one antidepressant has been sanctioned for use in children, the study found that doctors were prescribing a variety of mood-altering medications for young patients.

The researchers hope their findings provide a benchmark for assessing how the 2004 decision affects depression treatment in children, while reinforcing that antidepressants can be a valuable treatment tool if used appropriately.

"We're not saying that doctors should avoid prescribing antidepressants for kids, but we are pointing out the potential for inappropriate use of antidepressants," said Jun Ma, MD, PhD, research associate at the Stanford Prevention Research Center and lead author of the study that will appear in the December issue of the Journal of Adolescent Health. "If used as part of a comprehensive treatment regimen, antidepressants are of great benefit to individual patients and to the society as a whole."

The study comes amid continuing controversy over how best to treat depression in children. Depression affects between 2 and 8 percent of children and adolescents and is a major risk factor for suicide--the third-leading cause of death among U.S. teenagers. Ma noted that up until the early 1980s there were few effective medications to treat the condition in young patients.

The development of new antidepressants, particularly a class known as selective serotonin reuptake inhibitors or SSRIs, offered hope, but only one has been proven safe in children. To date, the FDA has approved only fluoxetine, an SSRI better known as Prozac, for patients under the age of 18. Prescribing any other antidepressant for children is considered "off-label" use of the medication. However, because roughly 40 percent of patients are not fully responsive to fluoxetine, physicians often seek out other medications for those patients.

In recent years, concerns were raised that some of the newer SSRIs heightened the risk of suicide among young patients, and in October 2004 the FDA required manufacturers of all antidepressants to include a "black-box" warning--the most serious type of warning on prescription drugs--describing the increased risk of suicide among adolescents taking such medications.

Guidelines issued by the American Academy of Child and Adolescent Psychiatry call for psychotherapy as first-line treatment for depressed children and adolescents. For the most serious forms of the mental illness, the guidelines recommend a combination of psychotherapy and medication so that health professionals can monitor the effects of the medication.

Ma and senior author Randall Stafford, MD, PhD, associate professor of medicine at the Stanford Prevention Research Center, are interested in research that examines how physicians change their practices in response to professional guidelines and to evidence generated by clinical trials. Realizing that the FDA actions would likely change the treatment of depression in adolescents, they began looking for data that would give them a baseline measurement. They discovered there was little available data, so they began working to amass the benchmark themselves.

To do this, they used two national databases that tracked outpatient visits to hospitals and physician offices between 1995 and 2002, and then assessed the number of visits for patients between the ages of 7 and 17 who were diagnosed with depression.

The researchers discovered a more than twofold increase in the number of visits associated with adolescent depression during those seven years, going from 1.4 million visits in 1995 to 3.2 million in 2002. "This change is a potential positive because depression historically has been underdiagnosed in children and adolescents," Ma said.

But the study also showed that the use of psychotherapy dropped from 83 percent of the visits in 1995 to 68 percent in 2002. Meanwhile, the use of medications rose from 47 percent in 1995 to 52 percent in 2002. "The mirroring pattern of these two types of treatment suggests that pharmacotherapy is increasingly used as a substitute, rather than a complement, for psychotherapy," Stafford said.

Although the percentage change in children receiving medication might not sound significant, Stafford added that with the increasing diagnosis of depression in children, the number using antidepressants has more than doubled. What's more, the researchers found that between 42 and 52 percent of the visits associated with medications didn't include counseling.

They also studied the types of medications prescribed to these patients. SSRIs accounted for 76 percent of the antidepressants prescribed to adolescents in 1995, rising slightly to 81 percent in 2002. Although fluoxetine remained the most-prescribed antidepressant, its share of SSRI use shrunk as newer drugs came on the market. In 1995, fluoxetine prescriptions accounted for 41 percent of the SSRI prescriptions for adolescents but dropped to 31 percent in 2002.

Although clinical trials are under way to assess the safety of other SSRIs in children and adolescents, little of the data has been published. Ma and Stafford said this means that when a diagnosis indicates a young patient needs an antidepressant, physicians should first try fluoxetine.

The researchers plan to revisit the issue in a few years to determine how the treatment of adolescent depression has changed since the FDA's actions. There is already some evidence of a shift. A September 2005 report by the American Psychiatric Association indicated that prescriptions for antidepressant medications for patients under the age of 18 dropped nearly 20 percent in the wake of the FDA warnings.

"We will be interested in assessing whether decreases in prescriptions have occurred selectively--that is, among patients where the indications for use are less clear--or whether physicians also have begun to withhold antidepressants in situations where the need is more definite," Ma said.

Also contributing to the study was Ky-Van Lee, PhD, a research analyst at the Stanford Prevention Research Center. The study was funded by the Agency for Healthcare Research and Quality.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions -- Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.