6/16/2010

ORGANIZATION OF TERATOLOGY INFORMATION SERVICESCONVERTING JAPAN &CONVERTING WOMENTO PAXIL
June 2010
DAVID HEALY MD
CARDIFF UNIVERSITYHastings
CenterReportsDec2009

G Koren 2007
The Way Women Perceive Teratogenic Risk
Can J Clin Pharmacology 14, e10-e16

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1962

Thalidomide
Distaval
Contergan

Senator
Estes
Kefauver
Democratic
Candidate
For Presidency
1952/1956
Chairman ofAnti-TrustCommittee

1959 Kefauver Harris Hearings
Prices Fixed and High4 Billion pages of Adverts
Adverts Fraudulent
Withholding Safety Data
77 countries surveyed,
28 allowed product patents
Drug prices 18 to 255 times higher“These drug fellows pay for a lobby
that makes the steel boys look like
popcorn vendors. …
anyone who dares seek the truth
will be accused of being apersecutor”
Estes Kefauver2

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1962 Amendments

1 Prescription only Status
2 Controlled Trials
3 Drugs for Diseases

Product Patents - TRIPs

2007
Zantac1985-1991
Prozac1991
Lipitor
1997
WEIGHT
InGOLD3

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February 7, 1990 Leigh Thompson Memo

BEECHAM’S PILLS
These renowned pills are composed entirely ofMedicinal Herbs [aloes, ginger and soap].. Cure constipation, Headache, Dizziness, Wind,Pain, and Spasms at the Stomach, Pains in the Back,
Restlessness, Insomnia, Indigestion, Want ofAppetite, Fullness after Meals, Vomitings, Sicknessof the Stomach, Bilious or Liver Complaints, Cold
Chills, Flushings of Heat, Lowness of Spirits, and all
Nervous Affections.. Pimples and Blotches on theSkin,.. Maladies of Indiscretion, Kidney andUrinary Disorders, and Menstrual Derangements“I am concerned about reports I get re UK attitude
toward Prozac safety. Leber (FDA) suggested a few
minutes ago we use CSM database to compare Prozac
aggression and suicidal ideation with otherantidepressants in UK. Although he is a fan of Prozac
and believes a lot of this is garbage, he is clearly apolitical creature and will have to respond topressures. I hope Patrick realizes that Lilly cango down the tubes if we lose Prozac and justone event in the UK can cost us that.”

1914

Converting
Japan to Paxil

1951

2000

1962
Because..

No SSRIs
Taijin Kyofu

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Response Rate%

Parachute v Placebo

100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%

ParachutePlacebo

56/16/201090%
80%
70%
60%
50%
40%
30%
20%
10%
0%

Antidepressants v Placebo

Penicillin
Placebo

Response Rate%

Response Rate%

Penicillin in Bacterial Endocarditis
v Placebo
50%
45%
40%
35%
30%
25%
20%
15%
10%
5%
0%

AntidepressantPlacebo

Stone and Jones 2006: FDA

Components of Therapeutic Response:
Antidepressant - Placebo
NNT Drug- 10
NNT Placebo- 2.5

Response Rate%

40%
35%
30%
25%

AntidepressantPlacebo

20%
15%
10%
5%0%
Stone and Jones 2006

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MEASURING OUTCOMES
1.
2.
3.
4.

Mean SASS Scores over Time

Antihypertensives & Quality of Life
Improved

Worse

Physician’s Patient’s
Relative’s
Assessment Assessment Assessment_____________________________________________

Physician’s Patient’s
Relative’s
Assessment Assessment Assessment____________________________________

Female341010433

Male41

2600341

0774

TOTAL

75

36

1

Disease Specific Observer Ratings- Hamilton Depression Scale
Disease Specific Subjective Ratings- Beck Depression Scale
Disease Non-specific Observer Rating- Clinical Global Impression Scale
Disease Non-specific Subject Rating- Quality of Life Scales

454035302520151050

RBX n = 38
FLX n = 36
PLC n = 25

Reboxetine
Fluoxetine
Placebo* P<0.05

D0

D7

D14

D21

D28

D35

D42

D49

D56

Jachuck et al 1982

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Asthma – Peak Flow

INSTRUCTIONS FORPULLING RABBIT OUT OF HAT

Lipid Levels
Blood Glucose

1/

PUT RABBIT IN HAT

2/

Eating Disorders
Osteoporosis
The Measurement
is the Illness“It may be that we are witnessing
a change as revolutionary
as was the introduction of standardizationand mass production in manufacture.
Both have their positive & negative sides".
Hamilton M (1972).

Rating Scales
1 Information poor checklists
2 Capture of Clinical Gaze
3 Measurement pseudo-science
4 Informational Reductionism

8

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LOWERED SEROTONIN LEVELS?

Clinical Research Organizations

Quintiles
ParexelCovance$30 Billion

1982
1983
1987

Trials in
Undeveloped
Countries
PrivateEthics
MarketingTrials
Data Access9

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From 2000 through 2006, Dr. Nemeroff
earned more than $960,000
from GlaxoSmithKline but listed earningsof less than $35,000 for the period on hisuniversity disclosure forms, according toCongressional documents.

New York Times April 10th 2008106/16/2010

The senator [Grassley] said records he obtained
from GlaxoSmithKline PLC, the maker of theantidepressant Paxil, indicated Dr. Stowe waspaid $154,400 by the drug company in 2007 and$99,300 during the first 10 months of 2008. The
totals included payments for at least 95
promotional talks on behalf of the company.

THE ANTIDEPRESSANT OF CHOICE FOR WOMEN

Japan
2000
No SSRIs

Paxil
SeroxatParoxetine
Depression in Women:
Times for Special Consideration•Premenstrual•Pregnancy•Postpartum

Pregnancy•Perimenopause

Short half life
Lactation
Untreated depression•Postmenopause

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THE ANTIDEPRESSANT OF CHOICE FOR WOMEN

PaxilSeroxat
Paroxetine

PreMenstrual Syndrome &PreMenstrual Dysphoric Disorder

Depression in Women:
Times for Special Consideration•Premenstrual
Short half life

•Pregnancy

PMS

PMDD

Lactation•Postpartum•Perimenopause

Untreated depression•Postmenopause

Primarily PhysicalSymptoms

PrimarilyMood
Symptoms

PMDD – PreMenstrual Dysphoric Disorder

PreMenstrual Dysphoric Disorder
Background

Symptoms• 75% of women report minor,
isolated, occasional
premenstrual changes• 20 – 50% report“premenstrual syndrome”• 3 – 8% of reproductive-age
women have PMDD

•Anxiety, irritability, tension•Affective lability•↓ Interest•↓ Energy, fatigability• Food craving• Bloating, breast tenderness,headaches, joint pain12

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Vaginal Atrophy
Osteoporosis

Hot Flashes
Coronary HeartDisease

Menopausal
Symptoms &Syndromes

Urinary Incontinence

Paroxetine For Hot Flashes In
Breast Cancer Patients• Rationale↓ Sexual Function

Depression– 55% survivors have debilitating Hot Flashes– Association between Estrogen RT – breast Cancer– Nonhormal treatment disappointing
Bellergal, clonidine, vit. E, soy products• Mechanism?
– estrogen withdrawal related to ↓ serotonin

Cognitive Decline

Postpartum
depression
Negative effect on
bonding

Noncompliance withprenatal care

SuicideRisks of UntreatedDepression During
Pregnancy

Effects on Foetus
Exposure toadditional
medications

Poor self-care,nutrition, sleep

Drug, alcohol,
tobacco

Altshuler et al. Am J Psychiatry. 1996; 153:592; Cohen et al. J Clin Psychiatry. 1998;59(suppl 2): 18; Meanet et al. Dev
Neurosci. 1996; 18:49; Orr et al. Epidemiol Rev. 1995; 17:165; Steer. J Clin Epidemiol. 1992;45:1093.

Zach Stowe

Emory
Women’sMental Health Program
These ‘perfect childbirth experiences’ accountfor less than 15%
of all pregnancies

13

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Seymour Kety
NIMH
1968

“The manipulation of the brain by any ofthe biological techniques which can bedeveloped in the foreseeable futurewould involve such drastic invasions ofprivacy, integrity and the unalienable rights of
the individualthat in their application behavioral control
would already have been achieved even if theelectrodes carried no current and the pill wereplacebo”.
S Kety, Hearings of the National
Commission on Health Sciences & Society.
90th Congress, Second Session. Page 292

Medicine & Markets
1．Collect the Right Data –Patient/Discovery
2.Access to Data – Free Market
3.Prescription Only?
4.Product Patents?

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