FDA panel urges "black box" warning for antidepressants
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《英国医生杂志》
All antidepressants should come with a "black box" label warning that adolescents treated with the drugs are more likely to become suicidal, according to an advisory panel to the US Food and Drug Administration.
Black box warnings are among the most stringent cautions issued by the FDA and are reserved for drugs with very serious or fatal side effects. The FDA generally follows the recommendations of advisory committees but is less likely to do so when the vote is split, as it was in this case (eight of the 23 expert panellists voted against the warning), said Dr Robert Temple, associate director for medical policy in the FDA’s drug evaluation centre.
The surprise vote came after the presentation of new analyses by the FDA during two days of hearings on 13 and 14 September showing that children taking the drugs were almost twice as likely to have suicidal thoughts or to attempt suicide as children receiving placebo.
The effects of a black box warning are variable. With some drugs, it has led to abrupt reductions in prescribing, but with others the warning seems to have had little effect. According to Joyce Generali, director of drug information at the Kansas University Medical Center, 192 drugs carried black box warnings by 14 July. The largest group with the warning is antineoplastic agents
Some panellists expressed concern that a black box warning could reduce the number of doctors willing to prescribe antidepressants in children. But Dr Thomas Newman, professor of epidemiology and paediatrics at the University of California, San Francisco, and a panellist, said: "We have very strong evidence of harm and not very strong evidence of efficacy. It wouldn’t be a bad thing if the use of these drugs were diminished."
The panellists decided to place the warning on all antidepressants rather than single out individual drugs. The only drug approved by both British and US medical authorities for the treatment of depression in adolescents, fluoxetine (Prozac), will also carry a black box warning. Dr Temple said he found it "interesting and persuasive" that all drugs, including fluoxetine, showed the same trend toward increased suicidality.
But Dr Matthew Rudorfer, assistant chief in the adult and geriatric section of the US National Institute of Mental Health, said: "Although antidepressants may cause two to three kids out of every 100 to be involved in a suicide related event, that is outweighed by the 15% of teenagers with untreated depression who commit suicide."
"That’s ridiculous," said Dr Peter Breggin, a psychiatrist and psychopharmacologist, whose work in the early 1980s led the FDA to require a new class warning for tardive dyskinesia.
"There isn’t one stitch of evidence that these drugs decrease suicidality. Quite the contrary: there is abundant evidence that they increase the risk."
Dr Breggin adds that Dr Rudorfer’s claim is "false" since the FDA studies showing a 2-3% rise in suicidality was based on "risk difference"—something that took into account the background rate of suicidality from depression.
Dr Breggin told the BMJ that a black box warning is not the strongest warning available to the FDA. "They could say the drugs are contraindicated. But the panellists, with their deep ties to industry, would never do that," he said. According to an FDA spokesperson, Jason Brodsky, 10 of the panellists received waivers because of financial conflicts of interest.
Dr Lawrence Diller, paediatrician and author of the two books on children and psychotropic drugs, testified in the hearings that "frontline doctors" are losing trust in researchers—especially when they learn about "eight negative studies on children that were never released to either doctors or the public. Dr Diller added, "The blame is clear. The money, power, and influence of the pharmaceutical industry corrupts all. Suppression of negative studies in the name of protecting stockholder interests, but at the cost of children’s health, highlights the amorality of an unfettered and unregulated market place."
The advisory panel also recommended that manufacturers should be required to attach a patient guide to the medicines describing the increased risk of suicidality in plain language. Dr Temple said the FDA hopes to reach a decision about the panel’s recommendations within a few months.(Bethesda, Maryland Jeanne)
Black box warnings are among the most stringent cautions issued by the FDA and are reserved for drugs with very serious or fatal side effects. The FDA generally follows the recommendations of advisory committees but is less likely to do so when the vote is split, as it was in this case (eight of the 23 expert panellists voted against the warning), said Dr Robert Temple, associate director for medical policy in the FDA’s drug evaluation centre.
The surprise vote came after the presentation of new analyses by the FDA during two days of hearings on 13 and 14 September showing that children taking the drugs were almost twice as likely to have suicidal thoughts or to attempt suicide as children receiving placebo.
The effects of a black box warning are variable. With some drugs, it has led to abrupt reductions in prescribing, but with others the warning seems to have had little effect. According to Joyce Generali, director of drug information at the Kansas University Medical Center, 192 drugs carried black box warnings by 14 July. The largest group with the warning is antineoplastic agents
Some panellists expressed concern that a black box warning could reduce the number of doctors willing to prescribe antidepressants in children. But Dr Thomas Newman, professor of epidemiology and paediatrics at the University of California, San Francisco, and a panellist, said: "We have very strong evidence of harm and not very strong evidence of efficacy. It wouldn’t be a bad thing if the use of these drugs were diminished."
The panellists decided to place the warning on all antidepressants rather than single out individual drugs. The only drug approved by both British and US medical authorities for the treatment of depression in adolescents, fluoxetine (Prozac), will also carry a black box warning. Dr Temple said he found it "interesting and persuasive" that all drugs, including fluoxetine, showed the same trend toward increased suicidality.
But Dr Matthew Rudorfer, assistant chief in the adult and geriatric section of the US National Institute of Mental Health, said: "Although antidepressants may cause two to three kids out of every 100 to be involved in a suicide related event, that is outweighed by the 15% of teenagers with untreated depression who commit suicide."
"That’s ridiculous," said Dr Peter Breggin, a psychiatrist and psychopharmacologist, whose work in the early 1980s led the FDA to require a new class warning for tardive dyskinesia.
"There isn’t one stitch of evidence that these drugs decrease suicidality. Quite the contrary: there is abundant evidence that they increase the risk."
Dr Breggin adds that Dr Rudorfer’s claim is "false" since the FDA studies showing a 2-3% rise in suicidality was based on "risk difference"—something that took into account the background rate of suicidality from depression.
Dr Breggin told the BMJ that a black box warning is not the strongest warning available to the FDA. "They could say the drugs are contraindicated. But the panellists, with their deep ties to industry, would never do that," he said. According to an FDA spokesperson, Jason Brodsky, 10 of the panellists received waivers because of financial conflicts of interest.
Dr Lawrence Diller, paediatrician and author of the two books on children and psychotropic drugs, testified in the hearings that "frontline doctors" are losing trust in researchers—especially when they learn about "eight negative studies on children that were never released to either doctors or the public. Dr Diller added, "The blame is clear. The money, power, and influence of the pharmaceutical industry corrupts all. Suppression of negative studies in the name of protecting stockholder interests, but at the cost of children’s health, highlights the amorality of an unfettered and unregulated market place."
The advisory panel also recommended that manufacturers should be required to attach a patient guide to the medicines describing the increased risk of suicidality in plain language. Dr Temple said the FDA hopes to reach a decision about the panel’s recommendations within a few months.(Bethesda, Maryland Jeanne)