Dialogue between MindFreedom Scientists and Zoloft Maker Pfizer

[Guest guest]

SSRI-Research@

Sat, 15 Jan 2005 22:38:09 -0500

[sSRI-Research] Dialogue between MindFreedom Scientists and

Zoloft Maker Pfizer

 

Preventive Psychiatry E-Newsletter # 168:

Letter from MindFreedom's Courageous Scientific Panel to Pfizer

 

(For the entire 3 letter exchange, go to:

http://www.mindfreedom.org

 

Scientific Panel

MindFreedom Support Coalition International

454 Willamette, Suite 216

PO Box 11284

Eugene, OR 97440-3484 USA

 

 

[TO]

 

Cathryn M. Clary, MD, MBA, Vice President

Psychiatry, Neurology, Consumer & Markets Development

Pfizer Global Pharmaceuticals

235 E. 42nd St 235/10/30

New York, NY 10017

 

Dear Dr. Clary:

 

David Oaks, Executive Director of MindFreedom Support Coalition

International has asked us to review your letter of response to our

letter of April 16, 2004 and to reply to it.

 

In your response you have again failed to answer our questions. You

cite two articles from peer-reviewed scientific journals. One is an

article entitled " Neurobiology of Serotonin in Depression and Suicide "

by Stockmeier in Volume 836 of the Annals of the New York Academy of

Science.

 

Stockmeier discusses several different avenues of research suggesting

that serotonin alterations are implicated in clinical depression. For

instance, he notes there have been 12 studies that examined the

postmortem brains of suicide victims, but he also points out that some

studies found an increased number of serotonin receptors while some

studies found no changes. Stockmeier's conclusion: " The current

results suggest that the number of serotonin-1A and serotonin-2A

receptors in the right prefrontal cortex or hippocampus are not

altered in suicide victims with major depression. " (p. 223).

 

In short, at best, Stockmeier talks about some interesting

possibilities but offers little in the way of specifics to back up

your claims.

 

You include the following quote from Stockmeier's article:

 

" Powerful evidence of an imbalance in serotonin neurotransmission in

major depression comes from the observation that the symptoms of this

disorder are relieved by repeated treatment with drugs that block the

reuptake or metabolism of serotonin. "

 

The use of the word " imbalance " in that quote is a breach of

scientific protocol in that it exaggerates and misrepresents what was

actually demonstrated by the research reported in the article. The

research merely demonstrated that a psychotropic drug had an effect on

the reuptake and metabolism of serotonin. To say that is evidence of

" an imbalance in serotonin neurotransmission " is erroneous because

nobody has demonstrated what the balance of serotonin transmission is

in the healthy human brain.

 

This is not quibbling or nitpicking. Determining the balance of

serotonin in the healthy brain would be a great scientific

breakthrough. Unfortunately, we haven't succeeded in achieving that

breakthrough yet. In the absence of that knowledge, to claim as you do

in your advertising that Zoloft " helps correct the chemical imbalance

of serotonin in the brain " is a misrepresentation of the truth.

 

The quote bases the evidence of imbalance on the " observation that the

symptoms of this disorder are relieved by repeated treatment with

drugs that block the reuptake or metabolism of serotonin. " We would

point out that the symptoms of depression are also relieved by

cocaine, heroin, methamphetamines and marijuana. As you know, all of

those drugs also inhibit the reuptake of neurotransmitters, including

serotonin. And they all have very damaging side effects on human

beings. Using the scientific principle of parsimony, we would infer

that the psychotropic drugs your firm manufactures and sells have

similarly damaging side effects. And, as you also know, there is

evidence that your drugs do increase the risk of violence and suicide

in people who use them, do inhibit sexual functioning and do create

problematic tolerance and withdrawal effects in users. In fact, after

its February, 2004 hearing on the impact of SSRI use on suicidal

ideation and behavior in children and adolescents, the United States

Food and Drug Administration ordered drug companies to add warnings of

these dangerous side effects to their drug labels.

 

In your letter you cite a textbook by Stephen A. Stahl entitled

Essential Psychopharmacology: Neuroscientific Basis and Practical

Applications. This is a textbook that discusses the mechanism of

action of many psychotropic drugs. It is an interesting book but it

hardly serves as documentation of a biological basis of mental illness.

 

Here are two quotes taken directly from the book:

 

" No single reproducible abnormality in any neurotransmitter or in any

of its enzymes or receptors has been shown to cause any common

psychiatric disorder. Indeed it is not longer considered likely that

one will be found, given the complexity of psychiatric diagnosis and

the profound interaction of environmental factors with genetics in

psychiatric disorders. " (p. 103).

 

" Since it was recognized by the 1960's that all the classical

neurotransmitters boost NE, DA and SHT in one manner or another, the

original idea was that one or another of these neurotransmitters, also

chemically known as monoamines, might be deficient in the first place

in depression. Thus, the 'monoamine hypothesis' was born. A good deal

of effort was expended, especially in the 1960's and 1970's, to

identify the theoretically predicted deficiencies of the monoamine

neurotransmitters. This effort to date has unfortunately yielded mixed

and sometimes confusing results. " (p. 45)

 

Stahl's conclusions seem very different from the standard advertising

slogans that are used to sell SSRI's.

 

In your letter you also cite an article entitled " The Serotonin

Transporter: A Primary Target for Antidepressant Drugs " by Schloss and

Williams in Volume 12 of the Journal of Psychopharmacology and include

the following quote:

 

" Decreased serotonergic neurotransmission has been proposed to play a

key role in the aetiology of depression. The concentration of synaptic

serotonin is controlled directly by its reuptake into the pre-synaptic

terminal and, thus, drugs blocking serotonin transport have been

successfully used in the treatment of depression. The therapeutic

effect of SSRI antidepressants is thought to result from an

enhancement of 5-HT neurotransmission due to long-lasting adaptive

changes in serotoninergic neurons. "

 

In this quote, the use of the phrase " key role in the aetiology of

depression " is another breach of scientific protocol, another case of

exaggeration and misrepresentation. In fact, there is no evidence that

decreased serotonergic neurotransmission has any role at all in the

aetiology of depression. There is only evidence that when some human

beings ingest a drug that has an effect on the reuptake of serotonin,

they experience relief from the symptoms of depression. That is only

evidence of a correlation between ingesting a substance and relief of

symptoms. It says nothing about the aetiology of the symptoms.

 

Correlation does not constitute causality. A causal relationship must

be proven by other than statistical correlation, a standard which

biopsychiatry has yet to meet.

 

As we pointed out in our last letter, we agree that Zoloft and the

other SSRI's act on the serotonin receptors. Although you continue to

state that this is the heart of the disagreement, it is not. What we

disagree about is your continued reference to evidence proving that

psychological distress results from altered neurotransmitter levels.

You continue to talk about these two ideas in the same sentence

implying that, if evidence documents that Zoloft acts on the serotonin

receptor, then that same evidence somehow proves that depression must

be due to a shortage of serotonin.

 

We have received a total of four letters from Pfizer, Inc. and the

American Psychiatric Association responding to our request for

scientific evidence that mental disorders are " biologically-based

brain diseases " and not a single letter has provided any specific

citations to support that claim.

 

We believe the aetiology of depression resides in the cognitive,

emotional and somatic experience of individuals as they struggle to

create meaningful and satisfying lives and that the biochemical

dynamics on which your drugs work are mediating rather than causative

variables.

 

In fact, the Schloss and Williams article is a somewhat speculative

review of research on the molecular structure of the serotonin

transporter and the chemical and electrical characteristics of the

serotoninergic system. It contains frequent use of words such as

" putative " (assumed to exist or have existed), " possible " and " proposed. "

 

On page 115 of the article, the authors write:

 

" The direct mechanisms underlying inhibition of (serotonin) transport

as well as the long-term, mood-modulating effects of these drugs are,

however, not yet understood. "

 

Reading the article leads one to question the wisdom of ingesting a

drug which affects a complex, intricate and critically important

organic system about which so little is known.

 

In your letter you say it is disingenuous of us to not have disclosed

our conflicts of interest. Apparently you consider clinical trial

researchers' undisclosed receipt of millions of dollars from

pharmaceutical companies, on the one hand, and efforts to advocate for

victims of harmful drugs and to study human health independently, on

the other, as equivalent conflicts of interest. Now that is truly

disingenuous.

 

Given the vast influence of drug companies over academic medicine and

clinical biopsychiatry, our questioning of the science behind

biopsychiatry actually limits our career opportunities.

 

The misrepresentation exhibited in the quotes and article you have

offered is precisely what we object to. Through such statements, you

create the impression that biopsychiatry and the widespread

prescription of psychotropic drugs rest on a solid scientific

foundation. Unfortunately, the media and much of the public have been

fooled by you. We haven't been and we think it is important that we

share our skepticism and concern as widely as possible.

 

We don't impugn the fundamental motivation of the people leading

Pfizer, Inc and other pharmaceutical companies. However, we believe

that, by continuing to misrepresent current scientific knowledge you

are doing a disservice to human beings and harming rather than helping

their efforts to achieve better levels of health and well-being.

 

Specifically, your web site contains the following statement:

 

" Although the way Zoloft works for depression, panic disorder, OCD and

PTSD is not completely understood, what is understood is that Zoloft

is a medicine that helps correct the chemical imbalance of serotonin

in the brain. "

 

We have asked you repeatedly for scientific evidence to support that

statement. You have sent us citations of textbooks and articles that

fail to meet the test of any established scientific standards to

demonstrate the truth of that statement. We, therefore, conclude that

your statement is not a true statement and wonder why you justify

continuing to state it.

 

Sincerely,

 

Fred Baughman, MD

Mary Boyle, PhD

David Cohen, PhD

Ty Colbert, PhD

Pat Deegan, PhD

Al Galves, PhD

Tom Greening, PhD

Keith Hoeller, PhD

David Jacobs, PhD

Jay Joseph, PhD

Jonathan Leo, PhD

Bruce Levine, PhD

Stuart Shipko, MD