Antidepressant Use in Children Soars Despite Efficacy Doubts
By Shankar Vedantam
Washington Post Staff Writer
Sunday, April 18, 2004; Page A01
The number of depressed American children being treated with antidepressants has soared over the past decade -- a tectonic shift in the practice of psychiatry -- but new scientific reviews of the research that fueled the trend suggest that the drugs' benefits have been dramatically oversold.
The use of antidepressants among children grew three- to tenfold between 1987 and 1996, data from various studies indicate, and a newer survey found a further 50 percent rise in prescriptions between 1998 and 2002. The explosion in antidepressant use occurred even though the vast majority of clinical trials have failed to prove that the medicines help depressed children.
The spike in prescriptions over the past five years has been especially sharp among children younger than 6, even though there is virtually no clinical trial data on these youngest patients.
Paradoxically, drugs that have never shown benefits for depressed children in clinical trials have some of the largest increases in prescription rates. Pediatric prescriptions for Paxil, for example, doubled between 1998 and 2002, even though the medicine failed to show it was any better than dummy pills in three trials. The drug has not been approved for use in children, and last year the Food and Drug Administration and British health authorities warned physicians not to prescribe Paxil for children, citing safety concerns.
Paxil is not alone. Of 15 trials conducted among depressed children, 10 failed to show antidepressants were better than dummy pills. Two were inconclusive, and three showed positive results. The negative results have mostly been withheld from public scrutiny by the pharmaceutical companies that paid for the trials, which say that the data are proprietary.
Although many psychiatrists swear by the drugs in children and adults, leading specialists agree they have limitations.
"These drugs are by and large efficacious, but they are only moderately efficacious," said Steven Hyman, former chief of the National Institute of Mental Health.
"A lot of clinical trials for antidepressants fail," added Hyman, now provost at Harvard University. "Partly that's the difficulty of trials in a waxing and waning disease, but we also need drugs of greater intrinsic efficacy."
Prozac remains the only antidepressant that the FDA has approved for children's depression, after the agency accepted two studies that demonstrated the drug worked better than dummy pills.
But an FDA internal analysis of the trials found Prozac failed on the statistical measure that researchers had originally chosen as their primary benchmark: "The evidence for efficacy based on the pre-specified endpoint is not convincing."
Senior officials at the agency, however, concluded that the improvement on another measure justified approval. For one of the studies, a senior official, Russell Katz, wrote in July 2001 that "one could argue that this post hoc choice of primary outcome is inappropriate," but in the end he and others said that this was the proper benchmark.
Australian researchers writing this month in the British Medical Journal reviewed the published studies of Prozac and other drugs and concluded they were consistently weak. The review charged that researchers doing the studies had selectively dramatized successes and glossed over problems.
Another analysis this month in the journal Psychiatric Services said the drugs had only modest benefits, with "many treated patients continuing to experience symptoms." The report tracked antidepressant prescription increases among children with private health insurance.
"When a patient takes a medicine or a family physician or a pediatrician prescribes medicine, their understanding when they hear this medicine works is they believe, 'My child will recover from depression,' " said Jane Garland, head of the mood and anxiety disorders clinic at the British Columbia Children's Hospital in Vancouver.
© 2004 The Washington Post Company