Kids and Antidepressants: A Growing Problem (cont.)
In an article in the Oct. 14 issue of The New England Journal of Medicine, Newman wrote that when FDA staff members analyzed results from randomized trials of antidepressants, "the results were striking. When all the pediatric trials were pooled, the rate of definite or possible suicidality among children assigned to receive antidepressants was twice that in the placebo group."
Psychotherapy Suicide Risk
Miriam Kaufman, MD, associate professor in the department of pediatrics at the University of Toronto and author of a book on helping teens overcome depression, agrees that there is evidence to show an increased risk of suicidality among teens who are started on therapy for depression. She notes, however, that increased suicidality is also seen among adolescents who have just started psychotherapy.
"The risk of suicidality is highest at the beginning of a depressive episode, regardless of treatment," agrees David. A. Brent, MD, professor of psychiatry, pediatrics, and epidemiology at the University of Pittsburgh School of Medicine. "We have data in press now showing that the incidence rate of suicidality in a psychotherapy trial we did is comparable to what has been reported in people treated with medication."
According to an article in the journal Pediatrics, about half a million children and adolescents in the United States each year receive prescriptions for SSRIs. From 1993 to 1997, the number of prescriptions for preschool and school-age children of three drugs, Prozac, Paxil, and Zoloft, grew threefold.
This phenomenon isn't limited to the United States, a Toronto-based child psychiatrist tells WebMD.
"In Canada, just under 2% of the pediatric population is prescribed antidepressants. Sounds small, but it's actually quite large, and the rate of prescribing psychotropic medications has risen dramatically over the last 10 years, even though rates of depression have not. So in other words, the rate of prescribing has gone up much more quickly than the prevalence rate of the disorder, so we have to ask why," says Marshall Korenblum, MD, associate professor in the department of psychiatry at the University of Toronto.
Korenblum tells WebMD that aggressive marketing by drug companies, including direct-to-consumer advertising (banned for prescription drugs in Canada, but not in the U.S.) may account in part for the explosion in sales of antidepressants for kids. But for doctors who prescribe them, the relative safety of newer generation antidepressants like SSRIs compared with older antidepressants known as tricyclic agents was a big selling point.
"If you take the SSRIs in overdose, they're safe. Teenagers would die if they took tricyclics because they have effects on heart, basically heart rhythm, whereas large, large amounts of SSRIs are quite safe. So physicians heard that and said, 'OK, these drugs are safe in the sense that if you overdose on them you're not going to die, and they were showing equal efficacy to the older generation. That's what the early [clinical] studies showed, and I think as a result, prescribing rates kind of took off."
Half Truths, Concealed Evidence
But as Craig J. Whittington, PhD, and colleagues from University College London in England reported in the April 24, 2004, issue of The Lancet, the benign view of newer antidepressants appears to have been based in part on half truths and concealed evidence.
While the researchers found that there was evidence to support the use of one drug, Prozac, in children and teens, the evidence -- both published and unpublished -- was weaker or negative in terms of risk-to-benefit ratio for Paxil, Zoloft, Effexor, and Celexa.
"Moreover, a possible increased risk of suicidal ideation, serious adverse events, or both, although small, cannot be ignored," they write.
In an accompanying editorial, Lancet editors decried the practice of withholding apparently unfavorable or questionable clinical evidence from consideration.
"It is hard to imagine the anguish experienced by the parents, relatives, and friends of a child who has taken his or her own life. That such an event could be precipitated by a supposedly beneficial drug is a catastrophe. The idea of that drug's use being based on the selective reporting of favourable research should be unimaginable," they write.
Risks Yes, but Benefits Too
Lost in the furor over increased suicidality and fudged trial results, however, is the evidence to suggest that newer antidepressants can offer significant clinical benefits to many young patients with depression, says Brent, who served on the FDA advisory committee and reviewed the evidence on antidepressants but was unable to attend the public meeting.
Brent tells WebMD that the growing evidence of increased suicidality has not caused significant changes in his practice.
"You have to explain to people the benefits and the risks, you have to monitor people for suicidality closely at the beginning of a depressive episode, the beginning of treatment anyway, and the only difference is that before you start an antidepressant, you need to explain to the family that there is a slightly increased risk of this happening," he says. "But at least for Prozac, where there's the most data, you're going to help many more people than are going to run into a problem with this. But in my opinion it is an acceptable risk-benefit."
What About Psychotherapy?
Brent is a pioneer of a form of psychotherapy known as cognitive behavioral therapy (CBT), which is based on the idea, backed by clinical evidence, that helping people to change the way they think can also help them change the way they feel. The technique has been shown to be effective in the treatment of depression and anxiety disorders.
But even he acknowledges that at least one SSRI, Prozac, appears to work well both in concert with psychotherapy and when used alone. He points to the recently published Treatment for Adolescents with Depression study (TADS) in which the investigators found that a combination of Prozac and CBT was most effective at treating teens with depression. In the study, however, CBT proved to offer only modest additional benefit, Brent says.