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Drug Company Experts Advised Staff to Withhold Data About SSRI Use in Children

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Drug Company Experts Advised Staff to Withhold Data About SSRI Use in Children PHARMACEUTICAL INDUSTRY A NALYSIS Drug company experts advised staff to withhold data about SSRI use in children An internal document advised ination of these data in order to staff at the international drug gi- minimize any potential nega- ant GlaxoSmithKline (GSK) to tive commercial impact.” withhold clinical trial findings in Sales for Seroxat amounted 1998 that indicated the antide- to almost $4.97 billion world- pressant paroxetine (Paxil in wide in 2003. North America and Seroxat in Study 329, conducted in the the UK) had no beneficial effect US from 1993–1996, was the in treating adolescents. largest trial to date on using an Paroxetine is 1 of 6 drugs in SSRI in a pediatric population. Health Canada the class of selective serotonin According to the document, the A 1993–1996 industry study reuptake inhibitors (SSRIs) that results indicated paroxetine was showed that paroxetine was no Britain and the US have since no more effective than placebo. more effective than placebo in banned for pediatric use because In the other trial, Study 377, treating pediatric depression. of increased risk of suicide. On carried out in Europe, South Feb. 2, Health Canada issued a America and elsewhere, placebo bility” (e.g., suicidal ideation/ public warning that the pedi- was actually more effective than gestures). Among the 95 patients atric use of 7 antidepressants — the antidepressant. taking the comparison treatment, paroxetine, bupropion (Well- The CMAt document ad- imipramine (Tofranil), there was butrin), citalopram (Celexa), flu- vised that “Positive data from 1 such case, and among the 89 voxamine (Luvox), mirtazapine Study 329 will be published in subjects receiving placebo there (Remeron), sertraline (Zoloft) abstract form at the [European was also 1. According to the ar- and venlafaxine (Effexor) — College of Neuropsychophar- ticle, only 1 serious adverse should proceed only after con- macology] meeting” in Novem- event — headache in 1 patient sultation with the treating ber 1998 and that “a full manu- — was considered by the treat- physician “to confirm that the script ... will be progressed.” It ing investigator to be related to benefits of the drug still out- also stated that “It would be paroxetine treatment. weigh its potential risks.” commercially unacceptable to Britain’s Medicines and The GSK internal document include a statement that efficacy Healthcare products Regulatory obtained by CMAJ offers a had not been demonstrated, as Authority (MHRA) advised doc- glimpse into the inner workings this would undermine the pro- tors in June 2003 that paroxetine of a drug giant. Entitled file of paroxetine.” should not be prescribed to pa- “Seroxat/Paxil Adolescent De- GSK spokeswoman Jill tients under the age of 18 because pression: Position piece on the McKinlay-Morris said that “the evidence from various clinical tri- phase III clinical studies,” the memo draws an inappropriate als showed that episodes of suici- confidential document was pre- conclusion and is not consistent dal behaviour were between 1.5 pared by the Central Medical with the facts.” She didn’t elab- and 3.2 times higher in children Affairs team (CMAt), a division orate on that point, but went on taking the drug than in those re- of SmithKline Beecham (which to say “GSK abided by all regu- ceiving placebo. Several nations, subsequently merged with latory requirements for submit- including the US, France and Glaxo Wellcome to form GSK). ting safety data. We also com- Ireland, quickly followed suit. The document provides municated safety and efficacy The MHRA subsequently re- guidance on how to manage the data to physicians through viewed and banned the pediatric results of 2 clinical trials con- posters, abstracts, and other use of 6 other SSRIs (exempting ducted into the efficacy of publications.” fluoxetine [Prozac]) and is now paroxetine (Seroxat). Given Study 329 was eventually reviewing their use among that the clinical trials results published (J Am Acad Child Ado- adults. The US Food and Drug were, according to the docu- lesc Psychiatry 2001;40[7]:762-72) Administration is now reviewing ment, “insufficiently robust” to in 2001. The authors concluded pediatric trials of 8 antidepres- support an application to regu- that paroxetine is “generally sants. It’s been estimated that as latory authorities for a label well tolerated and effective for many as 11 million American, change approving Seroxat for major depression in adoles- and 3 million Canadian children use in pediatric depression, cents.” Among the 93 adoles- are taking antidepressants. — CMAt recommended the firm cents taking Seroxat, there were Wayne Kondro, Ottawa, and Bar- DOI:10.1053/cmaj.1040236 “effectively manage the dissem- 5 serious cases of “emotional la- bara Sibbald, CMAJ CMAJ • MAR. 2, 2004; 170 (5) 783 © 2004 Canadian Medical Association or its licensors.
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