Fwd: [drugawareness] SF Chronicle-A Cure Worse Than Disease?-Part 1 of 2

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atracyphd2

Mon, 5 Jan 2004 03:49:05 EST

[drugawareness] SF Chronicle-A Cure Worse Than Disease?-Part 1 of 2

 

 

 

Please get this article/press release out to your local papers and chalenge

them to pick up the article and run it in the local press!

 

http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2004/01/04/CM118608.DTL

 

 

 

Sunday, January 4, 2004

 

 

 

 

 

A number of young women who take controversial antidepressant drugs, suffer

from emotional and behavioral changes. Some have attempted suicide, and some

have been successful. Read what parents aren't being told about their kids'

antidepressants.

_

 

Please Note: Tom and Kathy Woodward interviewed for the article below are our

directors for the International Coalition for Drug Awareness

www.drugawareness.org for the state of Pennsylvania. And Tom and Kathy are

available for

additional interviews, as are far too many other parents we work with

nationwide.

Feel free to contact us for any of their numbers.

 

And since I have worked as an expert witness in these cases for so many years

now, I have worked on both cases (Lacuzong and Schell) mentioned in the

article as well as comedian Phil Hartman's wrongful death case. And I have

consulted in cases with both attorneys, Don Farber and Andy Vickery. After 14

years of

working on this issue, testifying in the cases for 12 years, working with

thousands of patients and their families who are having reactions, and writing

an

almost 500 page book on the topic, I know a quite a bit about this issue. I

too am available for interviews even though time is getting tight with the FDA

hearing coming up Feb. 2.

 

Ann Blake Tracy, PhD

Executive Director, International Coalition For Drug Awareness

Author: Prozac: Panacea or Pandora? - Our Serotonin Nightmare

& audio tape on safe withdrawal: " Help! I Can't Get

Off My Antidepressant! " (800-280-0730)

 

Cell: 801-209-1800

Office: 801-282-5282

E-mail: atracyphd1

Website: www.drugawareness.org

________

 

 

 

 

 

A Suicide Side Effect?

 

What parents aren't being told about their kids' antidepressants

 

Rob Waters

Sunday, January 4, 2004

 

 

 

* Names and identifying details have been changed.

 

For 16-year-old Angela Reich*, 2002 was a year of hell. First, the Palo Alto

teenager was diagnosed with a rare form of highly aggressive cancer. Then she

went through months of debilitating chemotherapy that made her nauseous,

caused her hair to fall out and kept her in bed for much of her last year of

high

school. She handled it all with unflappable poise and good humor until it

seemed she was out of the woods. But the worst began when she started taking the

antidepressant Paxil.

 

" Angela had been just pushing through and pushing through, " says her mother,

Sara.* " She mustered all her strength and courage to face the chemo and to be

sick all the time. " By the end of the summer, with the most intense part of

her treatment behind her, she was worn out and discouraged. " She started to feel

overwhelmed and depressed. "

 

She began seeing a therapist and talked openly about her feelings. But after

a few weeks her depression had not lifted, and Angela asked about going on

antidepressants.

 

It took six weeks for the Reich's insurance company to approve a

psychiatrist, and by then Angela was in a deep funk. " She was not wanting to get

out of

bed in the morning, " Reich recalls. " She couldn't do her homework. She said it

felt terrible to live like this, but then she would say, 'I don't want to die,

I don't want to hurt myself.' I remember sitting across from her at the

kitchen table and tears pouring from her eyes and her saying 'This is so hard.'

"

 

The psychiatrist prescribed Paxil, a selective serotonin reuptake inhibitor

(SSRI) similar to its famous predecessor, Prozac. On a dose of 5, then 10, then

15 milligrams a day, Angela soon started feeling better. Five weeks after she

began taking the medication, Angela and her mother met with the psychiatrist,

who suggested another boost in dosage. " He said she's doing well now; she

could be doing even better on 20 milligrams, " Reich remembers. She was hesitant,

but Angela wanted her old life back and thought it made sense to try. The next

day, she started on the higher dose.

 

Restless Legs, Sleepless Nights

 

Within days, Reich says, her daughter was acting strangely. The first change

was Angela couldn't keep her leg still. " She'd be sitting in a chair and her

knee would be jerking up and down. " She became irritable and had more trouble

sleeping. Her parents would ask about her restless, jerking leg and she would

snap at them to leave her alone.

 

When Reich left on a business trip, Angela called her three or four times a

day and begged her to come home early. When she returned, Angela " burst in my

room and hugged me, " Reich says. " She kept saying, 'Mommy, I'm so glad you're

home.' She was scared, like she couldn't cope. She said she dreaded going to

bed because she had so much trouble sleeping. She'd lay there thinking and her

thoughts got darker and became unbearable. "

 

That night, Reich shared her daughter's bed but Angela slept little and was

still wound up in the morning. When her mother tried to get her ready for a

piano lesson, she said she wasn't going. " She looked funny and had a weird smile

on her face, " Reich remembers. " I knew something was wrong. I looked around

the room and saw some pill bottles. I asked if she took any pills and she said

'Yes.' "

 

Under questioning, Angela told her mother she had taken four tablets of the

sleeping pill Ativan. Then Angela ran to the bathroom, locked the door, and

started going through pill bottles. Her father, Jim, smashed the door open and

snatched a bottle of Benadryl from her hands. She ran to her purse, seized a

bottle of Tylenol and began shoving pills in her mouth. Her mother grabbed her,

pinned her arms, and marched her to the car, as Angela's younger brother

watched.

 

Reich drove straight to a nearby hospital. One block from the house, Angela

turned to her mother. " She said 'Mom, I don't know why I did that. It was like

something took me over.' And I said 'I know, it wasn't like you. But I will

keep you safe.' "

 

At the emergency room, the staff administered charcoal to absorb the drugs,

then transferred Angela to a psychiatric hospital. The next day, the hospital

psychiatrist called Reich. " He told me it was a drug-induced suicide attempt, "

she said, related to the increased dosage of Paxil.

 

Neither Angela, Sara nor her husband, Jim, an internal medicine doctor, knew

Paxil might carry a risk of triggering suicidal thoughts or actions. Aside

from a generic statement that depressed people are more likely to attempt

suicide, there is no mention of such a risk in Paxil's prescribing information.

 

England Acts, United States Follows

 

The risk Paxil may pose to children and teenagers burst into the news this

summer, when British regulators issued a warning urging doctors not to prescribe

the drug to children. They were acting on new data presented to United States

and British authorities showing that among 1,100 children enrolled in

clinical trials of Paxil, those taking the drug were nearly three times as

likely to

consider or attempt suicide as children taking placebos. " There is an increase

in the rate of self-harm and potentially suicidal behavior in this age

group, " said a statement from the British Medicines and Healthcare Products

Regulatory Agency (MHRA). " It has become clear that the benefits (of Paxil) in

children for the treatment of depressive illness do not outweigh these risks. "

 

Nine days later, the FDA issued a similar warning and announced that it would

conduct a detailed review of pediatric trials of Paxil, a review soon

broadened to include seven other antidepressants, including top sellers Prozac,

Zoloft and Effexor. In August, Wyeth Pharmaceuticals warned doctors that its

drug,

Effexor, triggered hostile behavior or suicidal thinking in children at twice

the rate as the sugar pills taken as placebos.

 

Then, last month, the MHRA announced that it was urging doctors to stop

prescribing a group of six antidepressants, including Paxil, Zoloft and Effexor

because they caused an increase in suicidal thoughts and actions. " These

products

should not be prescribed as new therapy for patients under 18 years of age

with depressive illness, " wrote Gordon Duff, chairman of the MHRA's Committee on

Safety of Medicines, in a " Dear colleague " letter to British physicians.

 

Prozac, the only SSRI approved for use in depressed children, was not

included in the new warning. The British review did not find a significant

increase

in the risk of suicide-related events among children taking the drug.

 

The British and American warnings were a stunning turnaround that left

thousands of parents whose children are using the drugs wondering whether their

children were at risk. But it was also long-sought vindication for a small group

of researchers, family members and lawyers who have been arguing for years that

antidepressants cause some people to become violently unhinged. They say

they've been frustrated in getting this word out to the public, in large part

because of the FDA's unwillingness to confront and control the drugmakers.

 

The FDA's warning about a possible suicide risk from Paxil left Sara and Jim

Reich feeling furious, betrayed, and ready to sue. " Had I known there was a

threefold increased risk of suicide among kids taking Paxil, I would not have

allowed my daughter to go on that drug, " said Jim. In fact, Jim has prescribed

the drug himself and is outraged that the Physician's Desk Reference, or PDR -

the drug bible for doctors, based on FDA-approved prescribing information -

says nothing about Paxil's suicide risk.

 

The British and American warnings also raised some troubling questions: How

did drugs that have been widely promoted as nearly risk-free, and that are

commonly prescribed by pediatricians and child psychiatrists, come to be seen as

potentially dangerous? What should parents whose children are taking them do

about it? And just how effective are these drugs that can sometimes cause such

serious problems?

 

An Uncontrolled Experiment

 

Since 1987, when Prozac became the first SSRI on the market, America's love

affair with antidepressants has worked its way down the age ladder. Between

1987 and 1996, the use of antidepressants and other psychotropic medications by

children and adolescents tripled, with most of that increase occurring after

1991, according to a recent study in the Archives of Pediatric and Adolescent

Medicine. By 1996, the study found, 6 percent of American children and teenagers

were taking psychotropic medications, one-third of which were

antidepressants.

 

Biological solutions to behavioral problems were becoming increasingly

acceptable, even fashionable. " I think there's been a revolution in the way

people

think about behavior, " says Lawrence Diller, a behavioral pediatrician in

Walnut Creek. " The idea that children's behavior is the product primarily of

their

genetics and biochemistry was promoted by American psychiatry and hijacked by

the drug industry. It's simply become more acceptable to see behavior as a

reflection of an imbalance in chemistry rather than an imbalance in life. "

 

The phenomenal growth in antidepressants prescribed to children leaves many

doctors and therapists uneasy. Diller, who has written about his misgivings in

two books ( " Running on Ritalin " and " Should I Medicate My Child? " ), cautiously

prescribes antidepressants to some children, but says the new data about a

possible link to suicide is making both him and some parents think twice. " It

hasn't caused me to stop using SSRIs, particularly in teenagers, but I think

it's another reminder that our information is incomplete. "

 

To understand how we got here, it's important to know a bit about the drug-

approval process. When a drug company applies to the FDA for approval to sell a

medication, it must demonstrate that the drug is safe and effective for a

particular population, such as adults, and a specific condition, such as

depression. Once the drug has been cleared by the FDA and is on the market,

doctors

are free to prescribe it to anyone for any reason. " Off-label " prescribing, is

quite common; the only real restriction is that drug companies cannot market

drugs to unapproved groups. From 1987, when Prozac was first approved for

adults, until early last year, when Prozac became the first SSRI approved for

use in

depressed children 7 and older, all antidepressants used by depressed

children were prescribed off-label.

 

The widespread use of antidepressants by children, critics say, amounts to an

uncontrolled national experiment. The prescribing physicians are often

pediatricians or family doctors with little or no training in

psychopharmacology.

The drugs are frequently given in the absence of therapy or other interventions.

The subjects of the experiment - children - are too young to give meaningful

consent. There is little understanding of the long- term effect these

medications have on the architecture of children's developing brains. And the

evidence

that the drugs are effective is less than impressive.

 

When Prozac was approved for depressed children last year, it was on the

strength of two controlled trials. One, published in 1997 in the Archives of

General Psychiatry, found that after eight weeks, 56 percent of kids taking

Prozac

showed some improvement, according to the clinicians who evaluated them,

compared with 33 percent of the kids in the placebo group. But 69 percent of the

kids taking Prozac still had significant symptoms of depression. Clinical trials

of Paxil, Zoloft and Effexor found those drugs to be no more effective than

placebos in treating depressed children.

 

Perhaps the most notable finding from clinical trials of antidepressants is

how many children respond well to placebos - as many as 59 percent in some

studies. This high placebo response rate is a common finding in pediatric drug

trials, in which children are generally seen once or twice a week by clinicians,

says David Healy, an internationally known psychopharmacologist from the

University of Wales College of Medicine who has emerged as a prominent critic of

drug company practices. " This suggests that simple support can help children in

many cases, " Healy says.

 

SSRIs: Cleaner and Safer?

 

In the years since 1987, SSRIs have developed a reputation for being largely

free of serious side effects, vastly improved over the older generation of

so-called tricyclic antidepressants. In some respects, this is true: Distressed

patients who attempt to kill themselves by overdosing are unlikely to succeed;

they can usually tolerate the pills. And patients taking tricyclics are more

likely to suffer from constipation, urinary retention, blurred vision and dry

mouth.

 

But SSRIs cause sexual problems at fairly high rates, as well as insominia,

nausea, dizziness and other side effects. Studies also have not found them to

be more effective than the older pills at relieving symptoms of depression.

" The SSRIs have sold themselves very heavily as safe and clean drugs compared to

the old antidepressants, " says Healy. " Well, it's not clear that they're

safer, and it's not clear that they cause fewer side effects. "

 

One side effect of SSRIs, recognized for at least 15 years, is a sensation

called akathisia, a restless agitation that ranges from jitteriness to a

sensation described by some people as " jumping out of their skin. " Healy

believes

akathisia is the principal trigger for impulsive violence in some people taking

SSRIs. " They became anxious, agitated, terrified, unable to sleep at night and

restless, " he says - the symptoms that plagued Angela Reich.

 

There have long been signs that SSRIs sometimes cause these reactions, which

drug manufacturers have tried mightily, and largely successfully, to keep out

of the public eye and off the labels. This issue first arose a couple years

after Prozac went on the market, amid a raft of media reports about grisly acts

of murder and suicide. The most notorious event took place in 1989, when

Joseph Wesbecker went on a shooting frenzy, killing nine fellow workers of a

Louisville, Ky., printing plant before turning his gun on himself. Wesbecker,

who

had a history of mental problems, was taking Prozac. No one could prove Prozac

caused his rampage, but by early 1991, some 350 suicides of Prozac patients had

been reported to the FDA, according to one former FDA official. Those

reports, which occurred outside the context of scientific clinical trials, were

dismissed as anecdotal and sensational by company officials.

 

Harder to dismiss, though, was a study published by Harvard researcher Martin

Teicher and two colleagues in the American Journal of Psychiatry in 1990

about six patients who developed " violent suicidal preoccupation " after taking

Prozac for two to seven weeks. " It was also remarkable how violent these

thoughts

were, " the authors reported. " Two patients fantasized, for the first time,

about killing themselves with a gun, " they wrote, while one placed a loaded gun

to her head, another had to be restrained to prevent self- mutilation, and

another fantasized about killing himself in a gas explosion. None of the

patients

was suicidal when they started taking Prozac, the researchers reported, and

their fixation with violence and death abated when they stopped.

 

Similar symptoms were noted the next year in a paper in the American Journal

of Child and Adolescent Psychiatry about six children ages 10 to 17 who

developed " intense self-injurious ideation or behavior " while taking Prozac.

After

three weeks on the drug, one 14-year-old girl, who had been depressed but never

suicidal, began cutting and otherwise injuring herself. She told hospital

staff, " I'm just waiting for the opportunity to kill myself, " and chanted,

" Kill, kill, kill; die, die die; pain, pain, pain, " according to the paper. The

Yale University authors noted the complexity of reaching any conclusion about

the

cause of these events since the children all had lengthy histories of

psychiatric difficulties that put them at risk for suicide. They also noted that

many

children taking Prozac become agitated, restless, and disinhibited and

developed insomnia to boot.

 

A 1998 paper by Roger Lane, a scientist at Pfizer, the maker of Zoloft,

stated that " all SSRIs have the rare potential to cause akathisia. " In its most

extreme form, Lane wrote, patients may feel that " death is a welcome result. "

 

Lane also warned that akathisia can sometimes be mistaken for worsening

depression, prompting some doctors to increase the dosage - and the danger.

Healy

agrees. " [Doctors] have been educated to think that SSRIs take four, five, six

weeks to work, " he says. " But they can cause problems long before that. "

 

In response to the Teicher paper and the growing media furor connecting

Prozac to acts of violence and suicide, the FDA in September 1991 convened an

extraordinary special hearing of its Psychopharmacological Drugs Advisory

Committee. Speakers told of family members who committed suicide or homicide

while on

Prozac and begged agency officials to ban or restrict the drug. But

representatives of Eli Lilly, maker of the blockbuster drug, backed by FDA and

academic

researchers, argued that suicide is an inherent risk among depressed patients.

The Lilly officials presented figures from the company's clinical trials

database suggesting that people on Prozac were at no greater risk of suicide

than

people taking placebos.

 

Committee members voted unanimously in Lilly's favor, and Prozac remained on

the market. No warning that the drug might induce violent or suicidal urges in

some people was added to its label.

 

'Cooking the Books'

 

The Prozac suicide controversy, and the huge number of suicide reports that

were streaming into the agency, reverberated inside the FDA, where two other

SSRIs, Paxil and Zoloft, were being considered for approval. The FDA medical

officer charged with reviewing Paxil's safety and efficacy data was Martin

Brecher, now an executive with the British pharmaceutical company Astra Zeneca.

" The

reports of successful suicide were coming in in bunches, " he said in a recent

deposition. " It was extraordinary, especially in comparison to other annual

reports where, you know, you had 20 reports of a cold and maybe two reports of

some liver enzyme elevations and here you are with 20 deaths in a report. "

 

Because Paxil and Zoloft were members of the same chemical class as Prozac,

the FDA asked officials at SmithKline Beecham (the predecessor to

GlaxoSmithKline) and Pfizer, Zoloft's maker, to submit reviews on the drugs'

effect on

suicidal behavior of patients. Brecher called Thomas Donnelly, a SmithKline

Beecham executive, and asked him to prepare such a report. In an internal

company

memo uncovered in a lawsuit, Donnelly described his conversation with Brecher,

noting that the FDA " does not see it as a real issue but rather as a public

relations problem. "

 

What happened next is controversial. Critics charge that the company

manipulated data to diminish the apparent suicide risk among Paxil users and

submitted

it to the agency. One of the harshest critics is an unlikely plaintiff's

attorney in San Rafael, a self described conservative Republican and retired

Navy

officer named Don Farber.

 

Farber, who has spent the better part of the past five years suing Glaxo-

SmithKline and other drug companies, is one of a handful of lawyers handling

such

cases. His first case involved a San Jose man, Reynaldo Lacuzong, who, in

1996, drowned his two children and himself in a bathtub three days after he

began

taking Paxil. After the suit was filed, GlaxoSmithKline and the surviving

Lacuzong family resolved the case with an undisclosed settlement.

 

The same thing has happened in dozens of other cases of alleged SSRI- induced

suicide or violence; few cases ever go to jury. In June 2001, however, a case

did. Three years earlier, Donald Schell, a 60-year-old Wyoming man, killed

his wife, daughter and granddaughter three hours after taking two tablets of

Paxil given to him as samples by his internist. Surviving family members sued

GlaxoSmithKline, and the jury awarded them $6.4 million for the wrongful deaths

of their relatives.

 

" [The company] knew there was a small group at risk and Don Schell was one of

those vulnerable people, " the family's attorney, Andy Vickery told the jury.

Farber makes the same argument: Drug companies have an obligation to warn

doctors and patients that these drugs can pose a threat to some people.

 

" If there was a warning that said 'Caution: this drug may cause suicide in

some people,' then doctors are going to know about it, " Farber says.

 

Instead of warning people, Farber charges, Glaxo-SmithKline tried to hide the

true numbers. " They cooked the books, " says Farber during a recent interview.

" They cheated on the results. And the FDA is part of this. "

 

Farber says the company manipulated the figures. Documents obtained by The

Chronicle show that in its initial application to the FDA, the company reported

that out of 2,963 adults taking Paxil during clinical trials in the United

States or other countries, seven patients killed themselves and 42 attempted

suicide. But in a review submitted in April 1991, in response to Brecher's

request, the seven suicides had dropped to five and the 42 attempts had gone

down to

40.

 

At the same time, the number of attempted suicides by patients taking

placebos doubled from three to six in the later review. The 1991 review also

acknowledges that two suicides and two suicide attempts charged to placebo

occurred

during a one-week " washout " period that came before the start of the study.

During that period, subjects were taken off any drugs they had been using to get

the drugs out of their system. Experts say it is inappropriate to count events

during the run-in period as placebo events.

 

Company officials admit there were errors made in reports filed with the FDA,

but deny any attempt to mislead. " There were unfortunately some

inconsistencies in how the data on suicide attempts was presented to FDA, " says

GSK

spokeswoman Mary Anne Rhyne. " When we became aware of this, we went back and

looked

at the clinical trial data again. GSK did not intentionally submit any

erroneous or misleading information to FDA. The suicide data submitted to FDA

explicitly identified when events occurred during the placebo run-in period. FDA

had

all this information right from the beginning. "

 

Farber contends that these small shifts in numbers make a big difference in

suicide rates. He claims that a close look at the data reveals that only one

placebo patient out of 554 attempted suicide, while 49 patients out of 2,963

taking the drug committed or attempted suicide - a ninefold difference.

 

Rhyne disputes this analysis. " The randomized, placebo-controlled data shows

no statistically significant differences in suicides or suicide attempts

between Paxil and placebo, " she says.