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Be Sure to Balance SSRI Benefits Against Risks


 

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.

The session came soon after the Food and Drug Administration's decision to require pharmaceutical companies to add a black box warning alerting prescribers to the risk of suicidal behavior with antidepressants in pediatric patients.

“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,” Dr. Ryan said.

When considering an SSRI in a pediatric patient, it's important to inform the family of the 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.”

He does, however, think that this kind of research is necessary. “We need to think about this finding in the context of risks and benefits. So, paradoxically, now is the time that we need more information about what are the benefits of SSRIs in kids,” he said.

Future research should focus on which subgroups of patients are at higher risk and when in the course of treatment they are at higher risk. 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.

It's also important to look at the bigger public health picture, Dr. Olfson said. “We need to be clear about the distinctions 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.

Those numbers stand in sharp contrast to the comparatively small number of kids who show up in emergency rooms and hospitals after actual suicide attempts, Dr. Olfson said.