America

1
Americas Children Need a Rescue Operationby
Vera SharavPresidentAlliance for Human
Research Protection

• ICSPP
• OCTOBER 13th - 14th, 2007
• Washington DC

2
What is FDAs 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 Vioxx withdrawn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
  marketeven after the lethal risks are known?
• What is FDAs 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 sponsors 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

• Industrys Willing Collaborators

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.
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 letters60 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/m
entalhealth_europesummary.htm
15

• A Survey of young child psychiatrists (2002)
• 9 of 10 (91) children referred 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 drugsTD USA Today, 2006
• Zach ADHD, anxiety, depression.
• Rx Ritalin, then Prozac, then Paxil ?manic.
• Prozac Zyprexagained 40 lbs in 5 months.
• His psychiatrist Rx Seroquelstill 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
  Disorder Vanderbilt University, Associated
  Press, 2006
• Black Box Warnings
• Increased mortality in elderly
• Other Serious Hazards
• acute weight gain (gt100 lbs),
• insulin resistance in children, type II
  diabetes,
• hyperglycemia, liver function 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 Syndromea.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

• 19972003 Children hospitalized with
  diabetes200 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 treatmentwithout regard for
  drug hazards.

27
Antipsychotics, U.S. SalesTMAP 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 gt 50
• Public funds 63 of MH spending
• gt 300 billion per year
• A Third Way Approach to Fix Americas 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 poor
  clinical performance, 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 drugsas chemical
  restraints across the U.S.
• At greatest risk disadvantaged, poor children
  treated within state mental health systems
• clinics, hospitals, foster care juvenile
  justice
• 5560 foster children
• multi-drug cocktails
• Even toddlers lt3 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
on 5 psych drugs. Risperdal was added to her
cocktail
13 year old Aliah Gleason
35

• New Jersey Medicaid 2006
• gt 39,000 children Rx psych drugs.
• 647 Rx for children aged 4 or less.
• Florida 2006 18,305 children Rx Antipsychotics
• 250 from 1999.
• Michigan Medicaid 2005
• 13,000 children lt17 Rx antipsychotics
  3,064 children aged 4 or less, Rx psych drug.
• 933 children lt 5 were Rx anticonvulsants
  972 children lt 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 advanceswe 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 dont know how accurately we can
  diagnose bipolar disorderThe label may or may
  not reflect reality. John March, NYT, 2007
• The number of children adolescents being
  diagnosed with bipolar disorder resulted in a
  significant rate 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.
• Were 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 Childrens Records

• MassHealth Reviews 82,900 records children lt 5
  to identify other preschoolers like Rebecca
  Riley.
• 955 children lt 7 Rx Clonidine
• 536 children lt 7 Rx Antipsychotic.
• Boston Globe, Oct. 7, 2007
• MassHealth only seeking children lt 5
• Rx at least three psych drugs 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 Rx 28 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
• 2004 BPD 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 concernThe effects (in kids) are
  similar to what we're seeing in adults.
• Thomas Laughren, Director, FDA Psych Products,
  2006

51
What is FDAs Safety Standard?

• We have not systematically looked at the data
  for children.
• 2007 FDA approved Risperdal for Autistic
  children, Zyprexa for teenseven as evidence
  demonstrates these drugs life-threatening
  metabolic hazards are even more severe in
  children.
• Thomas Laughren, director, FDA psychiatry
  products, 2006

52
Currently Recruiting 3-7 year olds

• We are seeing an increasing number of very young
  children, ages 3-7 years, with frank symptoms of
  BP disorder. Many of these young BPD patients
  have been treated with stimulants or
  antidepressants
• FDA-approved Protocol NCT00221403
• Valproate and Risperidone
• in 60 Young Children ages 3-7
• with Bipolar Disorders
• PI Robert A Kowatch, MD
• U Cincinnati
• Stanley Foundation

53

• Even before their first birthday, babies
  can suffer from clinical depression,
  traumatic stress
• disorder, and a variety of other mental health
• problems. Florida Strategic Plan for Infant
  Mental Health, 2001
• Surreal Rx for Disaster
• Psychopharmacology is on the horizon as
• preventive therapy for children with genetic
• susceptibility to mental health problems.
• David Willis, M.D., Medical Director, Pediatric
  News, January, 2004

54
Science or Science Fiction?

• One in ten children aged two to five had
• obvious signs / symptoms of psychiatric
• illnesses such as ADHD, anxiety or depression
• It suggests that such conditions begin
• very early in life, perhaps even in the womb
• Screening and treating these disorders in
• babies and infants is the way forward
• waiting until childhood or adulthood is too
  late.
• Dr. Adrian Angold, Duke BBC, Newsweek,
  11-2005

55
Actions to Protect Children

• AHRP Recommends
• Mandatory restrictions on access to Rx
  psychoactive drugs.
• Mandatory registry for doctors.
• Limit product promotion prohibit all advertising
  of drugs linked to mania, violent or psychotic
  behavior.
• Require physicians to provide parents with copy
  of FDA-approved label MedGuide.
• Require signed parental informed consent.