Medication & Melancholy
Unraveling the jumble of data on depression, drugs, and kids
Her journal entries practically sparkled with the hopes of any happy 12-year-old. And while Candace Downing's school worries may have been excessive for a perennial honor student, her luminous enthusiasm endeared her to everyone. Still, as sixth grade wore on, her normal need to achieve morphed into generalized anxiety disorder. Her psychiatrist said not to worry: The condition could be alleviated by a low dose of Zoloft and regular therapy visits.
Ten and a half months later, on Jan. 10, 2004, her mother, Mathy Milling Downing, found Candace hanging from the valance over her bed in their Laytonsville, Md., home. "There was never a note," Downing says, her words choked by tears. "An hour before, she was on her father's lap watching Animal Planet. This is what these drugs do to children."
Contrast the Downings' tragic story with that of Sherri Walton. Each of her three daughters has obsessive-compulsive disorder, and her oldest girl, Jordan, also struggles with depression. When she was 13, she sobbed to her mother, "I am a horrible person. I just want to kill myself." Walton realized that Jordan was not simply experiencing the puberty blues but was in the midst of a serious depression. A psychiatrist prescribed antidepressants, and after a month Jordan began to feel better.
During the past year, parents have been engulfed in information about the effectiveness and safety of using antidepressant drugs with children. Some reports say the drugs--called selective serotonin reuptake inhibitors, or SSRI s--are the best medicine for debilitating melancholy, while others say the drugs paradoxically increase the risk of suicide in young people. This scientific debate is what brought both Walton and Downing to hearings at the Food and Drug Administration. While Downing sat crying in the audience three weeks following Candace's death, Walton came to tell a positive story. She explained how this "beautiful 14-year-old was functioning and happy with life because of these meds." For Walton's family and others, the same drugs that others decry have created a normal life.
These are just two faces of the suicide and antidepressant debate: one, tear-stained and scarred by grief; the other, full of hope and relief. And in between these agonizing extremes are concerned doctors like John March, professor and chief of child and adolescent psychiatry at Duke University, who says: "It is very difficult in the cacophony of voices to discern the story that the data is telling us."
Fine lines. or some, the suppressed data from the pharmaceutical companies that suggested increased rates of suicide in people taking SSRI antidepressants made an irrefutable case for never prescribing these drugs to children. For others, subsequent research pointed to a direct correlation between increased prescriptions for SSRI s and decreased rates of suicide. But there are finer points of debate, like the differences between suicidal thoughts, suicide attempts, and actual suicide. How to calculate the benefits with the risks of antidepressants? Have antidepressant prescriptions overlooked both the fragility and the variety of children's brains?
It has not quite been a year since the FDA told manufacturers of antidepressants to place a black-box warning on the drugs, saying that antidepressants can cause suicidal actions in children and adolescents. Recently, the FDA modified its warning, saying the drugs "increased the risk of suicidal thinking and behavior in short-term studies of adolescents and children" with depression. Medco Health Solutions, a company that manages pharmaceutical benefits for employers and healthcare organizations, looked at the trends of how many patients under the age of 18 took the SSRI s from 2003 through 2004. It noted that from November to December 2004, after months of controversy, the number of children and adolescents taking antidepressants had decreased by 16 percent, compared with the same period the year before.
Sketchy data. Teenagers and adults in their early 20s are at the highest risk for suicide. Each year about 20 percent of adolescents contemplate suicide; by the end of high school, 1 in 10 has attempted it, with almost 2,000 succeeding each year. About half of those who die suffer from major clinical depression. Advocates for the use of antidepressants point out that the teen suicide rate increased from 5.9 to 11.1 per 100,000 between 1970 and 1994 but declined to 7.4 per 100,000 in 2002, just when the drugs were increasingly being prescribed for children.
These numbers reveal not only the scope of the problem but also the vast difference between the state of contemplating suicide--also called suicidal ideation--a suicide attempt, and an actual suicide. Ideation, it seems, is part of adolescence for 1 in every 5 kids in a high school classroom. A suicide attempt, however, becomes murkier in terms of reporting: Is self-cutting a suicide attempt or a way of relieving tension? Of course, it depends on the patient, but cutting alone, according to psychiatrists, is not attempted suicide.
Since the black-box warnings, two large-scale epidemiological studies have been published. One looked at international data, tracking the suicide rates of 27 countries over the past 20 years, from before the time antidepressant medication was introduced to after. "We saw a protective effect of people seeking treatment," says Dave Marcotte, a health economist at the University of Maryland-Baltimore County. On a county level, a study that compared prescription rates for antidepressants with suicide rates had similar findings.
But the studies did not focus on children, nor do they answer the most important question: What is the benefit of these drugs compared with the risk for children and teens? While for adults the data showing the benefits tend to be persuasive, for children and adolescents they are less so. "We are not where we can have someone come in with a certain profile and I will know before treatment what the risks are of feeling suicidal and gaining or losing lots of weight, versus having a terrifically positive response to treatment," says David Kupfer, chair of the department of psychiatry at the University of Pittsburgh School of Medicine. "I need to rely on group data, and that doesn't give all the information on benefit and risk."
Promising new research on the way serotonin behaves in the brain may eventually help clinicians figure this question out. In December, researchers from Duke University Medical Center found a mutation in a gene with a protein product that has a lot to do with the synthesis of serotonin. People with depression who carry this abnormal gene also show resistance to treatment with SSRI s.
Last month in the American Journal of Psychiatry, researchers reported one clue to treatment response might also be found in blood platelets. SSRI s work by blocking the serotonin reuptake transporter in the neurons; the transporter acts like a vacuum cleaner, controlling the amount of serotonin in the brain. When it is too aggressive, the brain is deprived of serotonin, which can lead to feeling depressed. As it turns out, blood platelets have serotonin reuptake transporters that are identical to the ones found in the brain, so researchers from the University of Pittsburgh looked at the blood of 23 depressed adolescents who were taking SSRI s. Researchers analyzed the patients' biochemistry before and after treatment and found that those who responded well to drug treatment had platelets that were much less sensitive to serotonin.
Another problem with the research has to do with the lumping together of age groups. A 6-year-old ballerina cannot possibly be evaluated in the same way as a 17-year-old football player. The brain pathways of prepubertal children are profoundly different from those of older teenagers, as are the ways they metabolize drugs. That leads many psychiatrists to be very reluctant to prescribe drugs for younger children. The placebo effect is also far stronger in children than in adults. "When a child gets into a clinical trial where there is a tremendous amount of attention and nurturing, they get better," says Charles Nemeroff, chair of the department of psychiatry and behavioral sciences at Emory University.
The questions swirling around the use of antidepressants are also deeply connected to the stigma of mental illness. "People don't think that depression is a real illness," says John Mann, professor of psychiatry and radiology at Columbia University Medical Center and the chief of the department of neuroscience at N.Y. State Psychiatric Institute. "If this whole question arose over cancer in children and adolescents, we wouldn't be having the same kind of black-box warnings. We have three out of three studies showing that these drugs work."
Of course, this is all academic for those who are convinced of the drugs' perils. But for others, life without these medicines is perilous. That's what makes these decisions so troubling, says Duke's March: "There is no conspiracy, no villain here; everyone is coming at this from different points of view, and the system isn't working." The stakes are high: "If we are going to prevent adult mental illness," March continues, "we need to figure out a public-health strategy for our children."
FOR MORE HELP
The Web offers a number of resources to help parents, physicians, and children untangle some of the often confusing safety information about antidepressant drugs. The first of the websites listed below, hosted by the American Academy of Child and Adolescent Psychiatry and the American Psychiatric Association, concludes that there is no documented connection between childhood and adolescent suicide and the use of antidepressant medication.
www.PhysiciansMedGuide.org
www.fda.gov/cder/drug/antidepressants
www.coolnurse.com/depression.htm
www.captn.org/
www.factsandcomparisons.com/sitepage.asp?ID=1000147
This story appears in the May 16, 2005 print edition of U.S. News & World Report.