Children and adolescents being treated with certain antidepressants may be at increased risk of suicidal behavior, the Food and Drug Administration said yesterday, setting the stage for tougher warning labels on the drugs.
The agency, releasing new analyses of 25 studies of 4,250 young psychiatric patients nationwide, said children and teens being treated with antidepressants appear nearly twice as likely to attempt suicide, think about it, or make suicidal preparations.
None of the young people in the mostly industry-sponsored studies committed suicide.
But the findings “are suggestive of an increased risk of suicidality,” said officials at the FDA, which will convene a meeting of national experts Sept. 13 and 14 to consider label changes.
The FDA announcement added to the controversy about pediatric use of antidepressants, a class of drugs known as SSRIs (selective serotonin reuptake inhibitors).
Though only one antidepressant, Prozac, has been specifically approved for treatment of childhood depression, other drugs including Paxil, Zoloft and Effexor are frequently prescribed “off label” for young people by doctors, who have the discretion to make drug-treatment decisions.
The widening use of such drugs has been followed by national and international reports of suicides and abnormal behavior among both young and adult users. As the FDA itself has noted, antidepressant users have exhibited symptoms including anxiety, agitation, panic attacks, hostility and mania.
In June 2003, the British government issued a strong warning against the use of GlaxoSmithKline’s Paxil in British patients under 18. A similar recommendation from the FDA to U.S. doctors followed.
In March, the FDA further urged 10 antidepressant drugmakers to add warning labels to their products saying both pediatric and adult patients should be monitored closely.
That FDA advisory came after one of its own scientists, epidemiologist Andrew Mosholder, concluded in February that an analysis of dozens of clinical trials showed that young antidepressant users had a significantly higher risk of hurting themselves while taking the drugs.
The FDA, which had faced congressional accusations that it was withholding Mosholder’s findings, asked Columbia University to reanalyze the clinical trials to see if suicide attempts had been correctly identified in them.
Columbia’s analysis found that even more young subjects in the studies had experienced “suicidal events.”
The Columbia findings, with Mosholder’s findings included, were released by the FDA yesterday and formed the basis of its cautionary words about antidepressant use in young people.
Yesterday’s FDA announcement on top of a series of studies showing that most antidepressants work no better in young people than placebo pills may discourage some doctors from prescribing the drugs.
“But the data is not black and white,” said Steven Hyman, Harvard University’s provost and former chief of the National Institute of Mental Health. “The biggest danger is that people will stop treating children for major depression. That would be even more dangerous.”
Three days ago, NIMH released a landmark, publicly financed study concluding that the best treatment for depressed adolescents is Prozac combined with standard talk therapy. Prozac has not shown the same link with suicidal tendencies as the other SSRI drugs.
Acknowledging the importance of that study, Robert Berkowitz, head of child and adolescent psychiatry at the Children’s Hospital of Philadelphia, said yesterday that doctors may still feel they have to try antidepressants other than Prozac when treating severely depressed young patients.
Confronted with a “profoundly depressed child or adolescent who is not responding to typical treatment, and under very careful clinical observation, a trial with another antidepressant might be warranted,” he said.
But much about the effects of antidepressants – both good and bad – remains unknown. Clinicians and researchers are not entirely sure that SSRI drugs contribute to suicide, and if they do, the mechanism is not understood. The drugs themselves may prompt negative behaviors. Or it could be that depressed patients who improve somewhat on the drugs also develop the energy and determination to kill themselves.