America’s Children Need a Rescue Operation by Vera Sharav President Alliance for Human Research Protection

1. America’s Children Need a Rescue Operationby Vera SharavPresidentAlliance for Human Research Protection ICSPP OCTOBER 13th - 14th, 2007 Washington DC

2. What is FDA’s Safety Standard? 1998-2005 FDA drug death Reports: 932 Vioxx deaths  Vioxx withdrawn 3,277 Clozaril death reports 1,093 Risperdal death reports 1,005 Zyprexa death reports Moore, Arch Internal Medicine, 2007 These antipsychotics continue to kill

3. How does a lethal drug gain FDA approval? How does it become a blockbuster seller? Why have children become primary consumers of hazardous drugs? Why do harm producing drugs remain on the market—even after the lethal risks are known? What is FDA’s responsibility? What must be done?

4. Without the willing collaboration of psychiatry, its leadership, academic institutions, and government, in particular, the FDA, industry could not have a stranglehold on medicine. And children would be protected from brain-damaging drugs.

5. Science transformed into Marketing Industry funds 80% of clinical trials spending $14 billion annually on transforming science into a controlled marketing tool. Companies engage in corrupt practices skewing trial results, concealing failed efficacy and lethal drug effects.

6. Companies control the data & results Analysis of every published trial comparing 5 new antipsychotics: 9 in 10 favored sponsor’s drug. "it appears that whichever company sponsors the trial produces the better antipsychotic drug." John Davis MD, American Journal of Psychiatry 2006

7. Academic “Authors” Academics have betrayed the public trust and undermined the integrity of science. Prominent academics signed off on ghostwritten promotional copy masquerading as science in medical journals declaring: ‘Atypical’ antipsychotics “safe & effective,” “well tolerated,” “with a more favorable side-effect profile.” They helped conceal failed trials and lethal effects.

8. A Glaxo PR firm found three psychiatrists willing to ‘author’ a ghosted letter for publication “minimizing Paxil withdrawal symptoms.” Dr. Bruce Pollack (U. Pitt) signed it. Industry’s Willing Collaborators The Journal of Clinical Psychiatry published it.

9. Absentee Guardian FDA fails to ensure that: “the public gets accurate, science-based information.” Physicians are misinformed by marketing propaganda masquerading as science. Physician ignorance about hazardous effects of drugs they prescribe poses a serious public health hazard.

10. FDA Derailed Rx Drug User Fee Act, 1992 FDA financially dependent on industry FDA Modernization Act, 1997 Fast-track approval overrides safety Financial incentives to test drugs on kids Daniel Troy, FDA Chief Counsel (2001-2004) argued: deceptive marketing is protected under 1st amendment.

11. FDA Focus Shifted dramatically 1999 –2001: FDA issued 250 "Warning" letters 2002 – 2004: only 70 letters—60% reduction FDA focus shifted from regulating drug marketing to protect the health and safety of consumers --toward shielding companies’ secrets about the hazards their drugs pose.

12. Industry spends $18.5 billion influencing doctors’ prescribing “Doctors are bombarded with deceptive messages in all areas of their professional life, when reading journals, attending conferences, meeting with sales representatives…” Abigail Caplovitz, NJ PIRG, 2006 FDA fails to use its authority to provide countervailing accurate information.

13. Worst Drugs are the most advertised Painkillers: Oxycontin, Neurontin COX-2 pain: Celebrex, Bextra Statins: Crestor, Lipitor, Zocor, Mevacor Sleeping pills: Ambien, Sonata, Lunesta Antidepressants: Prozac-Cymbalta, Paxil, Zoloft, Lexapro, Celexa, Effexor Antipsychotics: Zyprexa, Risperdal, Geodon, Seroquel Doctors Rx these drugs widely off-label

14. 6 Million U.S. Children Rx Psych Drugs Are American Children So Different? 2004: http://research.imshelath.com/research/mentalhealth_europesummary.htm

15. A Survey of young child psychiatrists (2002) 9 of 10 (91%) childrenreferred to a professional are Rx psychoactive drug – only 9% received psychotherapy. Stubbe, J Amer Acad Child Adoles Psyc, 2002 One of every 10 teenage boys who visits a doctor leaves with a Rx for a psych drug. 25% of teens Rx psych drugs "did not have an associated mental health diagnosis.“ Parks, Trends in Use of Psych Meds Adolesc, 1994 – 2001, Psychiatric Services, Jan. 2006

16. Commercially Driven Spiraling Rx Pattern "The bottom line is that the use of psychiatric medications far exceeds the evidence of safety and effectiveness. What people need to do is what's in the best interest of children instead of what's in the best interest of people's pocketbooks.” But children don't vote. Dr. Ronald Brown, APA Psych Meds Evidence, 2006

17. Are These Drugs Helping or Harming? “The most important finding of this review is that signs and symptoms of psychosis or mania, particularly hallucinations, can occur in some patients with no identifiable risk factors at usual doses of any of the drugs currently used to treat ADHD.”FDA ADHD Review 2006 ADHD drugs: “helping” kids “graduate” from difficulty staying on task to psychopathology and psychopharmacology

18. Rescue the Children Rex at 6: ADHD, Rx stimulant hallucinated about worms & bugs at 8: Rx Risperdal for “probable” OCD at 9: Dose increased, severe tremors Parents wean off drugs—TDUSA Today, 2006 Zach: ADHD, anxiety, depression. Rx Ritalin, then Prozac, then Paxil manic. Prozac + Zyprexa—gained 40 lbs in 5 months. His psychiatrist Rx Seroquel…still “aggressive” considers switching to Geodon… Sacramento Bee, 2002

19. ADHD Gateway to Antipsychotics "to me the most striking thing was that nearly one in five psychiatric visits for young people included a prescription for antipsychotics." Mark Olfson, MD Arch. Gen Psych, 2006

20. 2.5 Million US Children Rx Antipsychotics Most children Rx antipsychotics are not psychotic. Mostly Rx for unapproved “conditions” – ADHD, Autism, Oppositional Defiance, Conduct DisorderVanderbilt University, Associated Press, 2006 Black Box Warnings: “Increased mortality” in elderly Other Serious Hazards: acute weight gain (>100 lbs), insulin resistance in children, type II diabetes, hyperglycemia, liverfunction abnormalities, neuroleptic malignant syndrome, heart disease, stroke...

21. New neuroleptics: Worse than Old CATIE study confirms: No evidence drugs help patients recover. "the side effect outcomes are staggering in their magnitude and extent and demonstrate the significant medication burden for persons with schizophrenia… Sky-high drug discontinuation rates were seen, suggesting rampant drug dissatisfaction and inefficacy." Dr. Carol Tamminga, Editorial, AJP, 2006 Life-span shortened: possibly 25-years Colton & Manderscheid Mortality Rates, CMHS, CDC, 2006

22. Antipsychotics: Pathway to Metabolic Syndrome “Children and adolescents are at higher risk than adults for antipsychotic induced weight gain, metabolic abnormalities and elevated serum prolactin.” “Weight gain is a leading pathway to the metabolic syndrome and diabetes mellitus.” Correll and Carlson, J Amer Acad Child /Adolesc Psych 2006

23. Evolution of Metabolic Syndrome—a.k.a. Zyprexa Syndrome The Economist Newspaper Limited (2003), Cover illustration. The Economist; Dec. 13

24. Children Risk Insulin Resistance Johns Hopkins: All six children on moderate or high doses of antipsychotics, and 3 of 5 children on low doses -- evidence of insulin resistance. "The insulin resistance seen in these children was greater than what would be expected from weight gain alone, suggesting there is a factor distinct from excess weight that directly induces insulin resistance." Mark Riddle, M.D., director, Johns Hopkins U Child and Adolescent psychiatry, 2004

25. Children  Diabetes 1997–2003: Children hospitalized with diabetes+200% New York University School of Medicine 2001 to 2006 children, 10 to 19: Antipsychotic use: girls ………+117% boys……… + 71% Diabetes medications: girls…. + 59% boys…….... + 14% Diabetes type 2 medication girls……… +167% boys….….. + 33% MEDCO Health Solutions, 2007

26. TMAP = Rx blockbuster sales TMAP (Texas Medication Algorithm Project) concocted in 1995 under Gov Bush Collusion: pharmaceutical companies, U of Texas psychiatrists, state mental health & corrections officials. Exposed by Allen Jones TMAP mandates use of the most expensive psych drugs as first line treatment—without regard for drug hazards.

27. Antipsychotics, U.S. Sales:TMAP expands a small market

28. TMAP guidelines Rx for disaster Texas:Psychotropic drugs= 76% of all meds Rx for foster children. 1996-2000: Antipsychotic Rx children + 494% “Of youth receiving antipsychotics, 42.9% had no history of or current psychosis.”Behavioral Health Services & Research, 2004 Tennessee Medicaid: 1996-2001 Antipsychotics Rx children nearly doubled • from 23 to 45 per 10,000 children Rx for ages 6 to 12 + 93%; Rx for 13 to 18 +116% Rx for preschoolers + 61%

29. Medicaid Pays the Bill Since 2000 MH costs increased > 50% Public funds 63% of MH spending > $300 billion per year A Third Way Approach to Fix America’s Mental Health, 2005 “Nationwide, Medicaid programs purchase an estimated 60% to 75% of antipsychotic drugs.” San Francisco Chronicle, October 23, 2005

30. Antipsychotics -Total U.S. Sales $ in Thousands Rank Drug 2005 2004 2003 2002 2001 Class Total $10,471,598 $9,560,117 $8,406,791 $6,619,177 $5,374,591 Seroquel $2,596,076 $2,077,150 $1,572,050 $1,090,417 $703,666 Zyprexa $2,543,375 $3,016,650 $3,302,748 $2,972,044 $2,514,8093 Risperdal $2,310,229 $2,195,661 $2,117,131 $1,854,064 $1,622,8614 Abilify $1,540,020 $1,041,943 $365,656 $22,072 ***** Geodon $648,514 $514,304 $547,708 $253,124 $141,285 Source: IMS Health, IMS National Sales PerspectivesTM, 2/2006 1995-2000 Sales: $900 million  $4.8 billion 2001-2005 Sales: $5.4 billion  $10.5 billion.

31. Medco Health Solutions, 2007 Despite antipsychotics’ demonstrably poorclinicalperformance, despite their “staggering” adverse effects which are even worse in children and adolescents, off-label prescriptions for US children / adolescents surged by 82% from 2001 to 2006.

32. gynecomastia (male breast enlargement) is not much discussed in journals— Lawyers files provide the documentation. At 9 ½ Sean Rx Risperdal, developed breasts requiring surgical removal at 13 The scope, magnitude and nature of physiological harm produced by antipsychotics has been denied or trivialized by psychiatry, industry, and the FDA.

33. Rampant Drugging of Foster Children Abusive use of psychotropic drugs—as “chemical restraints” across the U.S. At greatest risk: disadvantaged, poor children treated within state mental health systems • clinics, hospitals, foster care & juvenile justice 55%—60% foster children • multi-drug “cocktails” • Even toddlers <3 are heavily drugged

34. “Medicating Aliah,” Mother Jones, 2005 4 SSRI Antidepressants Anti-anxiety drug 2 ‘Atypical’ Neuroleptics Old Neuroleptic 2 Anticonvulsants: Anti-Parkinson's drug At discharge from a State mental hospital Aliah was on5 psych drugs. Risperdal was added to her “cocktail” 13 year old Aliah Gleason

35. New JerseyMedicaid 2006: > 39,000 children Rx psych drugs. 647 Rx for children aged 4 or less. Florida2006: 18,305 children Rx Antipsychotics +250% from 1999. MichiganMedicaid 2005: 13,000 children <17 Rx antipsychotics 3,064 children aged 4 or less, Rx psych drug. 933 children < 5 were Rx anticonvulsants 972 children < 5 were Rx Antidyskinetics One child is currently Rx 17 psych drugs Ben Hansen, Northern Express, 2007

36. The Diagnosis Maze Paul Williams, 13, has had as many psychiatric diagnoses as birthdays: “Compulsive tendencies” “Oppositional defiant disorder” “pervasive developmental disorder” or some combination. Each diagnosis---a different regimen of drugs. At age 11 “bipolar disorder” — a whole new set of Rx. New York Times 11/ 2006

37. DSM-IV: Pathology Grab Bag

38. “Bipolar Child” Historically rare, now “highly prevalent” "Five years ago, pinning down bipolar disorder in children was like nailing Jello to the wall. Today, we've seen significant advances—we are now nailing cheesecake to the wall." “so far [genetic] research has not consistently shown increased occurrence of the disorder in children who are supposed to be at high risk.” Gabrielle Carlson, M.D. Psych News, 12-2-2005

39. Bipolar has Become a Catchall 40-fold increase in children diagnosed “Bipolar” “Psychiatrists made almost 90% of the diagnoses, and two-thirds of the young patients were boys” Olfson, Arch Gen Psych, 2007

40. DSM-IV Broadened Criteria “One factor that may have contributed to this increase is a revision in the diagnostic criteria of bipolar disorder in the Diagnostic and Statistical Manual (DSM. 1994).” Mark Olfson, 2007 “we simply don’t know how accurately we can diagnose bipolar disorder…The label may or may not reflect reality.”John March, NYT, 2007 “The number of children & adolescents being diagnosed with bipolar disorder… resulted in a significantrate of polypharmacy.” Jon McClellan, MD, Psychiatrist, Psych Times, 2005

41. Rebecca Riley “diagnosed” Bipolar age 2½. Psychiatrist Rx lethal drug Cocktail: antipsychotic, Seroquel; mood stabilizer, Depakote; blood pressure drug, Clonidine. Rebecca Riley, aged 4 Dead of multi-drug toxicity, 2007

42. Jos. Woolston, MD, Yale "probably tens of thousands of kids" are on random combinations of psychoactive medications. “We’re using them as guinea pigs, and not even keeping track of them." “Use of multiple psychiatric drugs in children has become ‘extremely common.’ The vast majority of kids are on at least two different medications and many are on three or four or five different medications.” Bloomberg News, 2006

43. MassHealth Children’s Records MassHealth Reviews 82,900 records children < 5 to identify other preschoolers like Rebecca Riley. 955 children < 7 Rx Clonidine 536 children < 7 Rx Antipsychotic. Boston Globe, Oct. 7, 2007 MassHealth only seeking children < 5 Rx “at least three psychdrugs” or an antipsychotic ?

44. Dennis Maltez, dead at age 12, Florida, May 2007 Dennis acquired multiple "diagnoses," including: autism, depression, schizophrenia, and mild retardation. Rx multiple psych drugs: Two antipsychotics— Seroquel and Zyprexa + anti-seizure drug Depakote.

45. 1.6 Million U.S. Children on Multiple Psychotropic drugs Lee, aged 9, was Rx a combination drug cocktail: 2 antidepressants + 2 antipsychotics. She descended into suicidal violence.Tampa Tribune, 2003 Stephen, 15, takes 2 antidepressants; anticonvulsant to stabilize his moods; a psychostimulant to improve concentration. Jacob, 14, takes a psychostimulant for concentration; an anticonvulsant; an antipsychotic; and an antihypertensive to induce sleep. Over three years, each boy Rx28 psychotropic drugs. New York Times, 2006

46. Erratic Inpatient Diagnosing Biological Psychiatry, 2007

47. National Hospital Discharge Survey 1996: Bipolar Disorder = least frequent diagnosis Children = 10% Adolescents = 10.2% Adults = 9.9% 2004BPD = most common diagnosis among Children = 40% Adolescents = 25.8% Adults = 14.9%

48. Children + 439% Adolescents + 296% “The increase was especially steep from 2002 through 2004 for black youngsters.” Psychiatry News, American Psychiatric Assoc, 2007

49. "We are using these medications and don't know how they work, if they work, or at what cost. It amounts to a huge experiment with the lives of American kids, and what it tells us is that we've got to do something other than we're doing now.” John March MD, Prof. child /Adolescent Psychiatry, Duke “We have to realize that we are risking treating children who could turn into obese diabetics with involuntary movements.” Neuroscientist Steven Hyman MD, Former Director, NIMH 2007

50. FDA denies drug-related casualties FDA MedWatch: +1,328 reports of serious antipsychotic side effects in children At least 45 deaths linked to antipsychotics 41 cases of Neuroleptic Malignant Syndrome— risk of death within 24 hours. MEDCO-USA Today, May, 2006 FDA: "we haven't been alerted to any particular or unusual concern…The effects (in kids) are similar to what we're seeing in adults.“ Thomas Laughren, Director, FDA Psych Products, 2006