WASHINGTON — It is important to balance risks with benefits when considering a selective serotonin reuptake inhibitor to treat a child or adolescent, several experts said at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
Among other things, session participants discussed the Food and Drug Administration's requirement of a black box warning alerting prescribers and patients to the risk of suicidal behavior with antidepressants in children and adolescents.
“I think this is very important. This is not a contraindication. This [warning] box is not telling clinicians that they can't use these drugs. What it's saying is that if a clinician is considering using an antidepressant in a child or adolescent, they need to consider the risk and balance that against the clinical need,” said Thomas Laughren, M.D., of the FDA's division of neuropharmacological drug products, Rockville, Md.
Selective serotonin reuptake inhibitors (SSRIs) do appear to work better than placebo in the short-term therapy of depression in children and adolescents, said Neal Ryan, M.D., of the Western Psychiatric Institute and Clinic in Pittsburgh. This is probably true in general, though fluoxetine is the only one with an indication for children.
Combining an SSRI with cognitive-behavioral therapy (CBT) might even be more effective, according to recent findings. In the Treatment for Adolescents with Depression Study (TADS), SSRIs combined with CBT showed the best results for treating depression. The results also suggested that pharmacotherapy is more effective than psychotherapy alone, but this finding needs to be duplicated in other studies, Dr. Ryan said.
For clinicians, the real problem is how to balance the increased short-term risk—an extra 2 per 100 patients who will either attempt suicide or exhibit suicidality because of the use of an SSRI—and the potentially decreased long-term risk of suicidal thoughts and behavior attributable to depression, Dr. Ryan said.
Clinicians are left with the dilemma of what to do about the next depressed child to come into the office: Pick an SSRI alone, choose psychotherapy alone, or combine an SSRI with psychotherapy. “I think we're going to have a rich debate on that,” he said.
When considering an SSRI in a pediatric patient, it's important to inform the family of potential risks and benefits and follow the FDA's monitoring suggestions. “I think also that we need to advocate for more studies. I think we're all scared that we won't get any more data on this question,” he said.
Mark Olfson, M.D., of Columbia University, New York, is not optimistic about the prospects for this type of research: “For the foreseeable future, I believe the pharmaceutical industry is going to view this whole area as radioactive and stay away from it.”
Future research should focus on which subgroups of patients are at higher risk and when in the course of treatment. One strategy would be to monitor depressed children closely for short periods of SSRI therapy, looking for somatic subjective dysphoria, changes in attention, changes in impulsivity, or other indicators of suicidality, Dr. Olfson said.
Dr. Ryan said that he sees a need for longer-term studies.
The long-term effects of the treatment of depression have not been studied. It may be that effective drug therapy for depression may decrease the long-term risk of suicide, but there is no clear evidence yet, he said.
It's also important to look at the bigger public health picture, Dr. Olfson said. “We need to be clear about the distinct-ions between suicidal ideation and the suicide attempts that were the subject of the randomized controlled trials analyses and actual suicide or serial suicide attempts that we encounter in practice.”
The rates of suicidal ideation and suicide attempts in a normal adolescent population also need to be considered. According to the Centers for Disease Control and Prevention's 2003 National Youth Risk Behavior Survey, 16.9% of normal adolescents in grades 9-12 had seriously considered attempting suicide in the previous 12 months and 8.5% had attempted suicide at least once in that time period, he noted.
“Those numbers stand in very sharp contrast to the comparatively small number of kids who show up in our emergency rooms and hospitals following actual suicide attempts,” Dr. Olfson said. “It's my own belief—that, in fact, the recent increase in the use of these medications in kids has actually saved lives.”