Fwd: [SSRI-Research] Concern Over Legitimacy of FDA¹s Review of Antidepressants and Suicide

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JustSayNo

Tue, 24 Feb 2004 09:12:09 -0500

[sSRI-Research] Concern Over Legitimacy of FDA¹s Review of

Antidepressants and Suicide

 

 

February 1, 2004

FOR IMMEDIATE RELEASE

 

Baum Hedlund

12100 Wilshire Blvd., Ste. 950

Los Angeles, CA 90025

Web: www.baumhedlundlaw.com

 

 

Concern Over Legitimacy of FDA¹s Review of Antidepressants and Suicide in

Children, Attorneys Claim FDA¹s Methodology Scientifically Illegitimate

 

Los Angeles, February 1, 2004<An FDA Advisory Committee meeting is scheduled

to take place on February 2, 2004 to review the risk of suicide in children

and adolescents taking the antidepressants Paxil, Zoloft, Prozac, Luvox,

Celexa, Effexor, Wellbutrin, Serzone, and Remeron. The FDA intends to

" determine whether those given antidepressants may have been, in aggregate,

at greater risk of committing suicide than those given inert pills.² (New

York Times.) In response, attorney for thousands of SSRI victims, Karen

Barth Menzies of Baum Hedlund, stated that " it would appear the FDA is

looking for ways to explain away the higher rates of suicide, not to

legitimately examine the issue.² Attorney Karen Barth Menzies will be

speaking at the public hearing Monday at the Holiday Inn in Bethesda, MD.

 

The FDA¹s announcement that it would be holding an advisory committee

meeting followed the UK government¹s December 10, 2003 announcement that all

SSRI antidepressants (except Prozac ) would be contra-indicated for use in

children and adolescents under 18 in the UK due to their lack of efficacy

and their association with suicidal thoughts and actions.

 

Baum Hedlund, a Los Angeles based law firm that represents thousands of

victims adversely effected by the SSRI antidepressants (including more than

20 families whose children either committed suicide or attempted suicide

while on an SSRI) is skeptical about the February 2, 2004 FDA Advisory

Committee Meeting.

 

First, an October 28, 2003 New York Times article stated that the FDA " plans

to re-examine many of the clinical conclusions made during studies of the

drugs. " In essence, the FDA proposes to second-guess the clinical judgment

of the researchers who had first-hand contact with these patients and who,

at the time, determined that the patients experienced a suicidal event

during the trial. In some instances, the researchers and the sponsoring

pharmaceutical company concluded that the suicidal event was caused by the

SSRI. Barth Menzies argues: " What the FDA proposes is scientifically

illegitimate and predestined to reach a favorable conclusion for the drug

companies. "

According to an overview memorandum issued by the FDA on January 2nd, the

FDA has enlisted the help of a group from Columbia University that,

according to the FDA, has a ³well-recognized expertise in adolescent

suicidality.² The FDA memo states that the group has ³developed an approach

to classifying events possibly representative of suicidality that precisely

fit [FDA¹s] needs.² (Memo, page 14.) However, according to David Healy, a

world renowned psychopharmacologist from the University of Wales College of

Medicine and an expert witness for plaintiffs: " The principles of clinical

trial randomization mean you cannot post hoc analyze to look for confounding

factors. "

 

Ironically, the drug companies themselves have argued, one for one, against

this position in litigation. For instance, GlaxoSmithKline¹s vice president

of clinical development testified that ³[a]t every single [clinical trial]

visit [by a clinical trial patient], it¹s one of the questions that is asked

[questions related to suicidality] . . ., so we are prospectively looking at

suicide in relation to our treatment every single time we study the drug.²

If that is the case, how is it appropriate, then, to post hoc reassess

events that clinical researchers identified as suicide events?

 

Another cause for skepticism is the Columbia University connection to the

advisory committee. Dr. John Mann (of Columbia) has significant financial

ties to the companies whose drugs are under scrutiny. Mann has also been a

defense expert witness for Pfizer and GlaxoSmithKline in litigation related

to SSRIs on this very issue. He is consistently relied upon by the companies

as a spokesperson to counter the claims that SSRIs cause suicide. Moreover,

Mann was the co-chair on a review conducted by the American College of

Neuropsychopharmacology (ACNP) which concluded (while admitting it did not

possess all the data) that the SSRIs are effective in treating children and

do not pose a risk of increased suicidality. (Nine out of ten of the ACNP

³task force² members have financial ties to the pharmaceutical companies in

question.) Moreover, some of the task force members are defending their own

studies that found the drugs safe and effective in children. For instance,

Dr. Karen Dineen Wagner, in August 2003, and shortly following the UK¹s ban

of Paxil for use in children, published a study which, according to the

author, demonstrated that Zoloft is effective and safe in children and

adolescents. In fact, Dr. Wagner conducted four Paxil studies, apparently

never published, which formed the basis, in part, of the UK's ban. Dr.

Wagner recently conceded, however, that this issue " requires further

investigation and looking at the entire database of these medications. " (The

Guardian.)

 

Notwithstanding, the Wagner study received a massive amount of positive

press coverage, touting Zoloft as a drug found safe and effective for

children and adolescents, no doubt orchestrated by Pfizer. However,

unbeknownst to those lacking a subscription to the Journal of the American

Medical Association (JAMA), the study has been seriously criticized by a

number of scientists through letters sent to the editor of JAMA, published

in the January 7, 2004 edition of the journal. One letter states: ³The

relative benefit increase of sertraline over placebo . . . suggests that

there might in fact be no benefit from sertraline for these patients.²

 

Another doctor stated: ³[Zoloft] barely achieved a statistically significant

improvement over placebo . . . I would appreciate more information about the

degree of influence the sponsor [Pfizer] had over the presentation of the

data and interpretation of the results. . . . Given the safety and efficacy

precautions recently raised about [Paxil], another selective serotonin

reuptake inhibitor with a similar mechanism of action (at least in adults),

I believe that more convincing data are needed before [Zoloft] can be

recommended as first-line treatment for major depression in children and

adolescents.²

 

Another letter complained that Dr. Wagner¹s claims about the study ³reach

well beyond the trial¹s results² and concluded ³this trial suggests that

[Zoloft] shows little to no perceptible benefit compared with placebo in the

treatment of depressed youths.²

 

Baum Hedlund has now learned that Dr. John Mann will be a member of the FDA

panel, according to a January 21, 2004 WebMD article. In response, Barth

Menzies stated: ³It¹s just a gross conflict of interest. It is beyond me

that the FDA would even consider having him on the panel or a participant in

reviewing the issue for the FDA. It¹s as if they have no concern whatsoever

about appearing unbiased.²

 

The timing of the ACNP¹s statement was no accident, less than two weeks

before the FDA advisory committee meeting, particularly given that the

report is Opreliminary¹ and ACNP admitted it Odid not have access to all the

data held by regulatory agencies and pharmaceutical companies.¹ So why was

it compelled to issue this preliminary and incomplete report at this time?

The report isn¹t even consistent with the FDA¹s own findings. At the same

time, it¹s hard to believe that the FDA was unaware of the task force or

that it would be releasing its preliminary findings when it did.²

 

Adding fuel to the already raging fire is the fact that two other members of

the ACNP task force will be members of the FDA advisory committee on

February 2 (Andrew C. Leon and Neil D. Ryan). If members of this ³task

force² can rush to make such bold conclusions knowing full well they do not

have access to all the data, how can they be expected to keep an open mind?

³It¹s just unbelievable. How can the FDA allow these people to participate

under the circumstances -- the whole process is becoming a farce,² stated

Karen Barth Menzies. ³Between Laughren¹s memo, the ACNP report and the

overlapping members on the advisory committee and ACNP, it seems clear that

FDA has no intention of following in the UK government¹s footsteps if doing

so can be avoided,² said Barth Menzies.

 

Ironically, the FDA memo does admit that when FDA ³re-reviewed² the data

submitted by the drug companies for pediatric approval, ³there were signals

of increased risk of suicidality for patients assigned to [the] drug.² In

addition, based on FDA¹s review of summary data later submitted to it by

drug manufacturers at FDA¹s request: ³A signal of increased risk on drug is

apparent for at least 4 of the 7 programs, i.e., paroxetine [Paxil],

sertraline [Zoloft], venlafaxine [Effexor], citalopram [Celexa], with

perhaps a weak signal for nefazodone [serzone].² The memo also states:

³While fluoxetine [Prozac] is generally without a signal, in the suicide

attempts analysis for study X065 there is actually a signal for drug.²

It should also be noted that a pivotal part of the British government's

determination concerned the drugs' lack of efficacy. The question of whether

these drugs are generally efficacious (even in the adult population) has

been a public issue for many years. In fact, according to an internal

memorandum written by a former FDA official, Dr. Paul Leber, there was some

concern within the FDA that the approval of Zoloft (for adults) may " come

under attack " because the FDA is not " as demanding as it ought to be in

regard to its standards for establishing the efficacy of antidepressant drug

products. "

Dr. Leber went on to state: " I have considered the fact that the evidence

marshaled to support [Zoloft's] efficacy as an antidepressant is not as

consistent or robust as one might prefer it to be. "

According to Leber, there were a number of studies (in adults) that " found

no difference between placebo and [Zoloft] treated subjects. " However,

Laughren in his memo defends the lack of efficacy found in the pediatric

studies, arguing that such failure can be expected. This is despite the

overall failure rate of 80%.

Another cause for skepticism is that the FDA, in the past year and a half,

has joined forces with drug manufacturers and against consumers in SSRI

litigation. For instance, the FDA intervened in favor of Pfizer, the maker

of Zoloft, in a Zoloft suicide case (Motus v. Pfizer) being litigated by

Baum Hedlund. The FDA took such action after its newly appointed Chief

Counsel, Daniel Troy, received a personal telephone call from Pfizer's

national counsel, Malcolm Wheeler, asking for help. Alarmingly, Baum

Hedlund learned that Troy worked for Pfizer during the pendency of that very

case. The FDA argued in the Zoloft suicide case that it would not allow

Pfizer to warn of a suicide risk even if it sought a warning. But the FDA

states in its January 2, 2004 memo that ³it has been part of medical lore

for many decades that antidepressants may have an early activating effect

that perhaps gives depressed patients the energy to follow through on

suicidal impulses before the mood improvement associated with antidepressant

treatment takes effect.² (Memo, page 2.) The same memo states that ³this

particular mechanism proposed to explain a possible increase in suicidality

early in antidepressant treatment is so well known that it is referred to as

the Oroll back¹ phenomenon² and ³if this view that initial antidepressant

treatment may be associated with an actual increase in risk of suicidality

is in fact empirically established, this would, in a sense, confirm a view

that is already widely prevalent in clinical lore, whatever the proposed

mechanism.²

In response, Barth Menzies stated: ³This is just incredible. Drug

manufacturers do not warn of this risk and thus, doctors -- primarily

general practitioners -- are unaware that such a risk exists. In fact, there

isn¹t a single reference in the collection of scientific literature known as

Medline that refers to Oroll back¹ in relation to suicidality. Furthermore,

how on earth can the FDA say on the one hand that it won¹t allow a drug

company to warn of a risk while on the other arguing that everyone already

knows of the risk. It¹s just internally inconsistent and absurd.²

According to Barth Menzies: " FDA has been violating its own mandate to act

in the interests of the American consuming public by taking sides with the

pharmaceutical companies it is supposed to police. The problem is not only

the cover-up by the pharmaceutical industry, it is the FDA's lack of

objectivity, which facilitates that cover-up. The consequences of this

complicity has, in far too many instances, led to tragedy and death. "