Most Antidepressants Are Too Risky for Children, Lancet Reports
28 April 2004
GlaxoSmithKline Plc's Paxil and similar antidepressants shouldn't be given to children because risks outweigh the benefits, said a Lancet study that analyzed unpublished data next to published data from clinical trials.
Inc.'s Zoloft, Wyeth's Effexor and Forest Laboratories Inc.'s Celexa were less effective, had more side effects or raised the risk of suicide more than reported in published studies, the Lancet study said. Only Eli Lilly & Co.'s Prozac showed benefits outweighing risks in unpublished data, the study said.
``In view of the high risk of suicide in this group of children and young people, the possibility that a drug might increase that risk without clear evidence of benefit, should discourage its use,'' researchers from the U.K. National Collaborating Center for Mental Health said.
European and U.S. regulators have reviewing the risks of medicines for depression, which strikes as many as 6 percent of children and teens. The U.S. Food and Drug Administration last month asked makers of antidepressants to change the labels on the drugs to warn about a higher suicide risk for adults and children.
The U.K. Medicines and Healthcare Products Regulatory Agency last year recommended against most antidepressants, except, Prozac, for children. European Union regulators yesterday recommended that Paxil not be given to children and adolescents because of risk of suicidal behavior.
Some 40,000 youth under age 18 years take antidepressants called selective
serotonin reuptake inhibitors, or SSRIs, in the U.K., with about half using
Prozac.
A Lancet editorial said the lack of published unfavorable data about these
medicines and children is ``an abuse of the trust patients place in their
physicians.''
``The story of research into selective serotonin reuptake inhibitor use in
childhood depression is one of confusion, manipulation and institutional
failure,'' said the editorial published in the April 23 Lancet.
Antidepressant sales reached $19.5 billion last year worldwide, and are the
third best-selling medicines in the U.S., behind cholesterol-reducers and ulcer
drugs, according to IMS Health Inc. Pfizer's Zoloft had worldwide sales of $3.4
billion.
Depression increases the risk of suicide, the third-leading cause of death among
adolescents and those in their early 20s, according to the U.S. National
Institute of Mental Health. Boys and men are more likely to kill themselves.
``When you find that a drug company is withholding data because it will damage market share, when you're talking about children with a high risk of suicide, that is potentially very serious,'' lead researcher Tim Kendall said in a telephone interview. ``Why aren't they publishing it?''
Paxil didn't reduce symptoms of depression while it raised the risk of suicide thoughts, attempts and side effects such as insomnia and anxiety, when data from two unpublished studies of 478 children were combined with a published study of 180, the Lancet study said.
No children killed themselves during any of the clinical trials examined in the Lancet study.
Zoloft's unpublished data from two published trials with 376 children suggested the drug was less effective than reported in a published study, and may have increased suicide thoughts and attempts, the study said. Celexa, in two unpublished trials involving 422 children, didn't reduce depression symptoms enough to show a benefit and raised the risk of suicide attempts and side effects, the researchers said.
Effexor also boosted the risk of side effects and suicide thoughts and suicide attempts, without reducing symptoms of depression, in two unpublished trials of 334 pediatric patients, the study found. The studies compared the antidepressants to dummy pills.
Meanwhile, Prozac showed no increase in ``suicidal behavior'' or suicide attempts, while it relieved symptoms of depression and was more likely to lead to remission of the disease, the study said. The researchers looked at unpublished data from two published Prozac studies of 315 children.
The researchers, all part of a group developing treatment guidelines on
childhood depression with funding from the U.K. National Institute for Clinical
Excellence, said none of the antidepressant makers were ``forthcoming'' with
unpublished studies.
``Drug sponsors who withhold trial data (or do not make full trial reports
available) undermine the guideline program, which can ultimately lead to
recommendations for treatments that are ineffective, cause harm, or both,'' the
study said.
Source: Bloomberg (UK), 23/4/2004