FDA hearings confirm risks of antidepressants
http://www.100md.com
《英国医生杂志》
Bethesda, Maryland
Testimony presented by experts at the first day of hearings held by the US Food and Drug Administration confirmed that depressed children who are treated with antidepressants are more likely to harm themselves than depressed children treated with placebo.
The hearings are being held jointly by the Psychopharmacologic Drugs Advisory Committee and the Pediatric Advisory Committee. Preliminary risk data on the use of antidepressant drugs in paediatric patients were presented at a joint meeting of two FDA committees on 2 February. Since that meeting, experts in suicidal behaviour in children assembled by Columbia University have independently classified the risks and the FDA has conducted an analysis of these data.
The analysis found that an earlier report carried out by Dr Andrew Mosholder of the FDA's Office of Drug Safety was justified. The Mosholder report, which evaluated data from 22 studies using nine drugs, was not published by the FDA when it was produced earlier this year, on the grounds that the reliability of events deemed to be "suicide related" were uncertain (7 August, p 307).
Dr Tarek Hammad of the FDA's Center for Drug Evaluation and Research said that Dr Mosholder's earlier conclusion that antidepressants were associated with an increased risk of self harm was justified
"Out of 100 patients treated, we might expect two to three patients to have some increase in suicidality due to short term treatment beyond the risk that occurs with the ," concluded Dr Hammad.
Dr Wayne Goodman, chairman of the Psychopharmacologic Drugs Advisory Committee, told the hearing the results are "the opposite of what we'd expect."
The FDA analysis by Dr Hammad included data from the treatment of adolescent depression study (TADS)—making a total of 24 studies analysed by the FDA.
Dr John March, lead author of the TADS study as published in JAMA ( 2004;292: 807), presented data to the committee from TADS that he said showed that the benefits of fluoxetine (Prozac), particularly in combination with cognitive behaviour therapy, outweighed the risks. Fluoxetine is the only drug approved for the treatment of adolescent depression in the United States and the United Kingdom.
Dr Goodman challenged Dr March about the lack of efficacy seen in TADS on a key primary end point, the children's depression rating scale, and asked whether, on the basis of the TADS data, fluoxetine would be able to be approved by the FDA for use in depression. Dr March answered that "technically" fluoxetine would not meet FDA criteria for approval but added that other end points were positive, indicating benefit.
The hearings, convened to assist the FDA in making possible regulatory recommendations, included extensive and often emotional testimony by the public. Parents of children who had hung, shot, or stabbed themselves to death spoke with voices cracking about how their children had become agitated or unable to sleep after beginning antidepressant treatment—symptoms they often attributed to akathisia, a side effect of the anti-depressants that they said drove their children to suicide.
Other parents read testimony from their children saying that they were doing well only because of the antidepressants they were taking (and in some instances only alive because of them).
Dr Goodman, saying that it seemed that many children have benefited from antidepressants, commented, "However, the data supporting that observation is rather elusive."(Jeanne Lenzer)
Testimony presented by experts at the first day of hearings held by the US Food and Drug Administration confirmed that depressed children who are treated with antidepressants are more likely to harm themselves than depressed children treated with placebo.
The hearings are being held jointly by the Psychopharmacologic Drugs Advisory Committee and the Pediatric Advisory Committee. Preliminary risk data on the use of antidepressant drugs in paediatric patients were presented at a joint meeting of two FDA committees on 2 February. Since that meeting, experts in suicidal behaviour in children assembled by Columbia University have independently classified the risks and the FDA has conducted an analysis of these data.
The analysis found that an earlier report carried out by Dr Andrew Mosholder of the FDA's Office of Drug Safety was justified. The Mosholder report, which evaluated data from 22 studies using nine drugs, was not published by the FDA when it was produced earlier this year, on the grounds that the reliability of events deemed to be "suicide related" were uncertain (7 August, p 307).
Dr Tarek Hammad of the FDA's Center for Drug Evaluation and Research said that Dr Mosholder's earlier conclusion that antidepressants were associated with an increased risk of self harm was justified
"Out of 100 patients treated, we might expect two to three patients to have some increase in suicidality due to short term treatment beyond the risk that occurs with the ," concluded Dr Hammad.
Dr Wayne Goodman, chairman of the Psychopharmacologic Drugs Advisory Committee, told the hearing the results are "the opposite of what we'd expect."
The FDA analysis by Dr Hammad included data from the treatment of adolescent depression study (TADS)—making a total of 24 studies analysed by the FDA.
Dr John March, lead author of the TADS study as published in JAMA ( 2004;292: 807), presented data to the committee from TADS that he said showed that the benefits of fluoxetine (Prozac), particularly in combination with cognitive behaviour therapy, outweighed the risks. Fluoxetine is the only drug approved for the treatment of adolescent depression in the United States and the United Kingdom.
Dr Goodman challenged Dr March about the lack of efficacy seen in TADS on a key primary end point, the children's depression rating scale, and asked whether, on the basis of the TADS data, fluoxetine would be able to be approved by the FDA for use in depression. Dr March answered that "technically" fluoxetine would not meet FDA criteria for approval but added that other end points were positive, indicating benefit.
The hearings, convened to assist the FDA in making possible regulatory recommendations, included extensive and often emotional testimony by the public. Parents of children who had hung, shot, or stabbed themselves to death spoke with voices cracking about how their children had become agitated or unable to sleep after beginning antidepressant treatment—symptoms they often attributed to akathisia, a side effect of the anti-depressants that they said drove their children to suicide.
Other parents read testimony from their children saying that they were doing well only because of the antidepressants they were taking (and in some instances only alive because of them).
Dr Goodman, saying that it seemed that many children have benefited from antidepressants, commented, "However, the data supporting that observation is rather elusive."(Jeanne Lenzer)