Fwd: Antipsychotic Use in Children: FDA Panel Rejects FDA Soft-Peddle Approach

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ALLIANCE FOR HUMAN RESEARCH PROTECTION Promoting Openness, Full Disclosure, and Accountability http://www.ahrp.org and http://ahrp.blogspot.com FYIThe New York Times reports that an FDA advisory committee deliberating overthe safety of using antipsychotic drugs in children--e.g., Risperdal andZyprexa--rejected agency officials' effort to downplay these drugs'documented hazards which are magnified in children."The committee's concerns are part of a growing chorus of complaints aboutthe increasing use of antipsychotic medicines in children and teenagers.Prescription rates for the drugs have increased more than fivefold forchildren in the past decade and a half, and doctors now use the drugs tosettle outbursts and aggression in children with a wide variety ofdiagnoses, even though children are especially susceptible to their sideeffects."Indeed, from 1993 through the first three months of 2008, 1,207 childrengiven Risperdal suffered serious problems, including 31 who died. Among thedeaths was a 9-year-old with attention deficit problems who suffered a fatalstroke 12 days after starting therapy with Risperdal.The Times reports, "Food and Drug Administration officials proposed that thecommittee endorse the agency's routine monitoring of the safety of themedicines in children and support its previous efforts to highlight thedrugs' risks. But committee members unanimously rejected the agency'sproposals, saying that far more needed to be done to discourage themedicines' growing use in children, particularly to treat conditions forwhich the medicines have not been approved."Dr. Thomas Laughren, director of the FDA's division of psychiatryproducts--the FDA official who had been most instrumental in providing theFDA seal of approval for antipsychotics without highlighting the veryserious risks of harm the drugs posed--is quoted saying, "I'm a littlepuzzled about the statement that the label is inadequate.... the agencycould do little to fix the problem."This statement is disingenuous.In point of fact, we believe evidence exists showing that Dr. Laughrenactively promoted the increased use of antipsychotics in children.He did so when none of these had been approved by the FDA for use inchildren. He promoted the use of these highly toxic drugs in ghostwritten publicationsas a co-author with influential academic psychiatrists whose financialconflicts of interest and biased reports have invalidated the psychiatricliterature.  Some of these authors' financial conflicts of interest--Drs.Charles Nemeroff, Alan Schatzberg, Melissa DeBello-- have been laid bare bySen. Grassley.Dr. Laughren also co-authored a book chapter with Leigh Thompson (then) EliLilly's chief  scientific officer. (Premarketing safety evaluation ofpsychotropic drugs.)Dr. Laughren's other influential industry-funded co-authors include Drs.Graham Emslie, Carole Tamminga, Peter Jensen, David Shaffer, FrederickGoodwin...as well as Dr. Trei Sunderland whose concealed conflicts of interest led toa criminal verdict.Partial bibliography of Dr. Laughren's publications:1. Consensus Report on Impulsive Aggression as a Symptom Across DiagnosticCategories in Child Psychiatry: Implications for Medication Studies.SPECIAL COMMUNICATION. Journal of the American Academy of Child & AdolescentPsychiatry. 46(3):309-322, March 2007.Authors.  JENSEN, PETER S. M.D.; YOUNGSTROM, ERIC A. Ph.D.; STEINER, HANSM.D.; FINDLING, ROBERT L. M.D.; MEYER, ROGER E. M.D.; MALONE, RICHARD P.M.D.; CARLSON, GABRIELLE A. M.D.; COCCARO, EMIL F. M.D.; AMAN, MICHAEL G.Ph.D.; BLAIR, JAMES M.D.; DOUGHERTY, DONALD Ph.D.; FERRIS, CRAIG Ph.D.;FLYNN, LAURIE B.A.; GREEN, EVELYN B.A.; HOAGWOOD, KIMBERLY Ph.D.;HUTCHINSON, JANICE M.D.; LAUGHREN, TOM M.D.; LEVE, LESLIE D. Ph.D.; NOVINS,DOUGLAS K. M.D.; VITIELLO, BENEDETTO M.D. Abstract: Objective: To determine whether impulsive aggression (IA) is a meaningfulclinical construct and to ascertain whether it is sufficiently similaracross diagnostic categories, such that parallel studies across disordersmight constitute appropriate evidence for pursuing indications. If so, howshould IA be assessed, pharmacological studies designed, and ethical issuesaddressed? Method: Experts from key stakeholder communities, including academicclinicians, researchers, practicing clinicians, U.S. Food and DrugAdministration, National Institute of Mental Health, industry sponsors, andpatient and family advocates, met for a 2-day consensus conference onNovember 4 and 5, 2004. After evaluating summary presentations on currentresearch evidence, participants were assigned to three workgroups, examinedcore issues, and generated consensus guidelines in their areas. Workgrouprecommendations were discussed by the whole group to reach consensus, andthen further iterated and condensed into this report postconference by theauthors. Results: Conference participants agreed that: A is a substantial publichealth and clinical concern, constitutes a key therapeutic target acrossmultiple disorders, and can be measured with sufficient precision thatpharmacological studies are warranted. Additional areas of consensusconcerned types of measures, optimal study designs, and ethical imperatives.Conclusion: Derived from scientific evidence and clinical experience, theseconsensus-driven recommendations can guide the design of future studies. 2. Mood disorders in the medically ill: scientific review andrecommendations.Biol Psychiatry. 2005 Aug 1;58(3):175-89. Review. Authors: Evans DL, Charney DS, Lewis L, Golden RN, Gorman JM, Krishnan KR,Nemeroff CB, Bremner JD, Carney RM, Coyne JC, Delong MR, Frasure-Smith N,Glassman AH, Gold PW, Grant I, Gwyther L, Ironson G, Johnson RL, Kanner AM,Katon WJ, Kaufmann PG, Keefe FJ, Ketter T, Laughren TP, Leserman J, LyketsosCG, McDonald WM, McEwen BS, Miller AH, Musselman D, O'Connor C, Petitto JM,Pollock BG, Robinson RG, Roose SP, Rowland J, Sheline Y, Sheps DS, Simon G,Spiegel D, Stunkard A, Sunderland T, Tibbits P Jr, Valvo WJ.3. Methodological issues and controversies in clinical trials with child andadolescent patients with bipolar disorder: report of a consensus conference.J Child Adolesc Psychopharmacol. 2003 Spring;13(1):13-27. Review. Authors: Carlson GA, Jensen PS, Findling RL, Meyer RE, Calabrese J, DelBelloMP, Emslie G, Flynn L, Goodwin F, Hellander M, Kowatch R, Kusumakar V,Laughren T, Leibenluft E, McCracken J, Nottelmann E, Pine D, Sachs G,Shaffer D, Simar R, Strober M, Weller EB, Wozniak J, Youngstrom EA.4. Developing strategies for psychopharmacological studies in preschoolchildren.J Am Acad Child Adolesc Psychiatry. 2003 Apr;42(4):406-14. Review. Authors:  Greenhill LL, Jensen PS, Abikoff H, Blumer JL, Deveaugh-Geiss J,Fisher C, Hoagwood K, Kratochvil CJ, Lahey BB, Laughren T, Leckman J, PettiTA, Pope K, Shaffer D, Vitiello B, Zeanah C.5. Developing novel treatments for mood disorders: accelerating discovery.Biol Psychiatry. 2002 Sep 15;52(6):589-609. Review. Authors: Tamminga CA, Nemeroff CB, Blakely RD, Brady L, Carter CS, Davis KL,Dingledine R, Gorman JM, Grigoriadis DE, Henderson DC, B Innis RB, Killen J,Laughren TP, McDonald WM, M Murphy GM Jr, Paul SM, Rudorfer MV, Sausville E,Schatzberg AF, Scolnick EM, Suppes T.Contact: Vera Hassner Sharavveracare212-595-8974THE NEW YORK TIMESNovember 19, 2008Use of Antipsychotics in Children Is CriticizedBy GARDINER HARRISWASHINGTON - Powerful antipsychotic medicines are being used far toocavalierly in children, and federal drug regulators must do more to warndoctors of their substantial risks, a panel of federal drug experts saidTuesday.More than 389,000 children and teenagers were treated last year withRisperdal, one of five popular medicines known as atypical antipsychotics.Of those patients, 240,000 were 12 or younger, according to data presentedto the committee. In many cases, the drug was prescribed to treat attentiondeficit disorders.But Risperdal is not approved for attention deficit problems, and its risks- which include substantial weight gain, metabolic disorders and musculartics that can be permanent - are too profound to justify its use in treatingsuch disorders, panel members said."This committee is frustrated," said Dr. Leon Dure, a pediatric neurologistfrom the University of Alabama School of Medicine who was on the panel. "Andwe need to find a way to accommodate this concern of ours."The meeting on Tuesday was scheduled to be a routine review of the pediatricsafety of Risperdal and Zyprexa, popular antipsychotic medicines made,respectively, by Johnson & Johnson and Eli Lilly & Company. Food and DrugAdministration officials proposed that the committee endorse the agency'sroutine monitoring of the safety of the medicines in children and supportits previous efforts to highlight the drugs' risks.But committee members unanimously rejected the agency's proposals, sayingthat far more needed to be done to discourage the medicines' growing use inchildren, particularly to treat conditions for which the medicines have notbeen approved."The data show there is a substantial amount of prescribing for attentiondeficit disorder, and I wonder if we have given enough weight to theadverse-event profile of the drug in light of this," Dr. Daniel Notterman, asenior health policy analyst at Princeton University and a panel member,said when speaking about Risperdal.Drug agency officials responded that they had already placed strongly wordedwarnings on the drugs' labels."I'm a little puzzled about the statement that the label is inadequate,"said Dr. Thomas Laughren, director of the agency's division of psychiatryproducts. "I'm anxious to hear what more we can do in the labeling."Kara Russell, a spokeswoman for Johnson & Johnson, said, "Adverse drugreactions associated with Risperdal use in approved indications areaccurately reflected in the label."But panelists said the current warnings were not enough.While panel members spoke at length about Risperdal, they said theirconcerns applied to the other medicines in its class, including Zyprexa,Seroquel, Abilify and Geodon.The committee's concerns are part of a growing chorus of complaints aboutthe increasing use of antipsychotic medicines in children and teenagers.Prescription rates for the drugs have increased more than fivefold forchildren in the past decade and a half, and doctors now use the drugs tosettle outbursts and aggression in children with a wide variety ofdiagnoses, even though children are especially susceptible to their sideeffects.A consortium of state Medicaid directors is evaluating the use of the drugsin children on state Medicaid rolls to ensure that they are being properlyprescribed.The growing use of the medicines has been driven partly by the suddenpopularity of the diagnosis of pediatric bipolar disorder.The leading advocate for the bipolar diagnosis is Dr. Joseph Biederman, achild psychiatrist at Harvard University whose work is under a cloud after aCongressional investigation revealed that he had failed to report to hisuniversity at least $1.4 million in outside income from the makers ofantipsychotic medicines.In the past year, Risperdal prescriptions to patients 17 and youngerincreased 10 percent, while prescriptions among adults declined 5 percent.Most of the pediatric prescriptions were written by psychiatrists. From 1993 through the first three months of 2008, 1,207 children given Risperdal suffered serious problems, including 31 who died. Among the deathswas a 9-year-old with attention deficit problems who suffered a fatal stroke12 days after starting therapy with Risperdal.At least 11 of the deaths were children whose treatment with Risperdal wasunapproved by the F.D.A. Once the agency approves a medicine for aparticular condition, doctors are free to prescribe it for other problems.Panel members said they had for years been concerned about the effects ofRisperdal and similar medicines, but F.D.A. officials said no studies hadbeen done to test the drugs' long-term safety.Dr. Dure said he was concerned that doctors often failed to recognize themovement disorders, including tardive dyskinesia and dystonia, that canresult from using these medicines."I have a bias that extra-pyramidal side effects are being under-recognizedwith these agents," Dr. Dure said.Dr. Laughren of the F.D.A. said the agency could do little to fix theproblem. Instead, he said, medical specialty societies must do a better jobeducating doctors about the drugs' side effects.Copyright 2008 The New York Times CompanyFAIR USE NOTICE: This may contain copyrighted (C ) material the use of whichhas not always been specifically authorized by the copyright owner. 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