[SSRI-Research] Suicide: Accutane: Man spends $1 million to investigate drug whi

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Thu, 27 Jan 2005 21:52:02 -0500

[sSRI-Research] Suicide: Accutane: Man spends $1 million to

investigate drug which he alleges caused his son's suicide

 

 

 

 

 

http://www.usatoday.com/news/health/2005-01-26-accutane-usat_x.htm

 

Grieving father spends $1 million nest egg to investigate Accutane

 

By Kevin McCoy, USA TODAY

 

Liam Grant says he's sure his son's acne medication caused the Irish

university student to commit suicide.

 

By Julien Behal, Getty Images, for USA TODAY

 

So sure he's spent roughly $1 million of his retirement nest egg on

scientific research examining the effects of Accutane, the acne drug

manufactured by Roche.

 

So sure that he helped organize a Web site aimed at restricting use of

the drug and investigating what the manufacturer knows about its safety.

 

And so sure that he rejected a settlement offer from Roche and several

co-defendants that could total at least hundreds of thousands of dollars.

 

Early next month, Grant is scheduled to square off with a division of

the Swiss-based pharmaceutical giant for a hearing in a Dublin court.

If he prevails at the proceeding, which comes as a U.S. congressman

seeks a Washington hearing on Accutane's safety, Grant could move

closer to obtaining internal company records about the drug. That, in

turn, could provide legal ammunition for plaintiffs in roughly 70

pending Accutane cases in the United States, where there have been few

settlements involving suicide or depression.

 

The 57-year-old forensic accountant says he's optimistic about the

David vs. Goliath confrontation. " How do you bring an elephant to the

ground? Small bites, " said Grant during one in a series of recent

telephone interviews. " That's what I'm doing. Small bites. "

 

In response, the company said: " Roche feels a great deal of sympathy

for Liam Grant regarding the loss of his son, but according to a

significant body of scientific evidence, there is no cause-and-effect

relationship between Accutane and psychiatric events. "

 

Accutane, introduced in the USA in 1982 to treat severe acne that

fails to respond to other drugs, is safe when prescribed and used

appropriately, Roche says. Many dermatologists and acne patients also

say it's more effective than other drugs.

 

By Tannen Maury, Bloomberg News

 

A 'significant body of scientific evidence' shows Accutane is safe,

Roche says.

 

However, the drug has been linked to birth defects among children of

pregnant women who have taken it. A Food and Drug Administration

researcher told a Senate committee in November that Accutane was one

of five drugs that should be studied for potential withdrawal from the

market. Moreover, since the late 1990s Accutane's label has warned

that adverse reactions reported by some users include " depression,

psychosis, and, rarely, suicidal ideation, suicide attempts and suicide. "

 

But regulators in the USA and Europe hadn't yet required that warning

when Grant's 19-year-old son, also named Liam, went to his family

doctor in November 1996 for acne treatment.

 

The younger Grant, one of four siblings, was an engineering student at

University College Dublin. His father says Liam played guitar and

drums in bands and hoped to launch a career recording music.

 

Medical records show that Liam did not suffer from the severe,

treatment-resistant acne for which Accutane is prescribed. Dr. Pamela

Mangal prescribed an antibiotic, then wrote a stronger prescription in

December when Liam was unhappy with the results. One month later, she

referred him to Dr. Gillian Murphy, a dermatologist, who prescribed

Roaccutane, the drug's market name in Ireland. Liam started taking it

in February 1997.

 

His father says he should have noticed the potential warning signs

that ensued. Liam, previously outgoing and enthusiastic about his

plans, increasingly spent time alone in his bedroom. When friends

called, he asked one of his brothers to tell them he was unavailable.

 

Jury investigates

 

In June 1997, Liam was found dead, hanging from a tree outside Dublin.

A jury, impaneled to investigate the case, ruled the death a suicide

and called for more research on Accutane and its side effects.

 

Grant, backed by his wife, Loyola, and three surviving children, took

on the mission.

 

First, he hired a local scientific researcher to check the drug's

history. She discovered that France had added a suicide warning to

Accutane's warning label in 1997, during the time Liam had taken the drug.

 

Grant said he wrote to dermatology associations asking them to conduct

research on the possible brain effects of Accutane or urge Roche to

undertake such studies. Receiving no response, he decided on an

unusual scientific research program: He'd fund some study costs

himself by selling two real estate properties he'd bought as part of

his retirement portfolio.

 

He sought out scientific experts at universities in the USA, with the

aim of prompting unprecedented research about Accutane. In

Massachusetts, he made contact with the University of Massachusetts

Medical School and the Eunice Kennedy Shriver Center. In Atlanta, he

contacted Emory University.

 

Although rare, the move isn't unprecedented. Cure Autism Now is a

group founded by families to raise funds and seek research that would

help relatives suffering from the mysterious disorder. Similarly,

Texas billionaire H. Ross Perot paid for research on illnesses

afflicting U.S. soldiers who served in the 1991 Persian Gulf War.

 

So far, Grant funded two studies aimed at securing government grants

for additional Accutane research. Results from one, published last

April in the Proceedings of the National Academy of Sciences, showed

that the active component of Accutane reduced cell creation in the

brains of mice that had received clinical doses. In turn, that outcome

appeared to impair the mice's ability to learn a maze task.

 

Could the medication have a similar effect on the human brain? " We can

suggest it is a possibility, but we can't say that's the case

absolutely, " said Peter McCaffery, a University of Massachusetts

Medical School researcher who worked on the project.

 

The second study is undergoing scientific peer review, a vetting

process designed to spot any weaknesses or mistakes, in preparation

for March publication in the American Journal of Psychiatry.

Twenty-eight acne sufferers underwent initial brain scans, along with

psychological tests that ruled out any connection between their acne

and whether they felt depressed.

 

Key dates in Accutane's history

 

1971: Roche develops Roaccutane, called Accutane in the USA.

1982: Food and Drug Administration approves Accutane to treat severe

acne that is unresponsive to other treatments.

1986: Roche changes Accutane's package insert to say some users had

reported depression symptoms.

1988: Public Citizen petitions the FDA for a ban on Accutane.

1997: French regulators require Roche to list suicide as a potential

side effect. A Roche doctor studies data on depression in Accutane

patients, leading him to recommend users be supervised for signs of

depression and, if necessary, referred for treatment.

February 1998: FDA says Accutane's packaging will include a warning

that some users have reported adverse reactions including depression,

psychosis and " rarely, suicidal ideation, suicide attempts and suicide. "

March 1998: Health regulators in Britain and Ireland require warnings

of Accutane's risk of psychiatric disorders.

December 1999: Roche prepares a " Psychiatric Disorder Issue Work-Up "

for the FDA, concluding that none of the 168 reports of suicidal

behavior can be directly linked to Accutane.

May 2000: Roche changes Accutane's package warning label to include

possible side effects involving depression, rare suicidal thoughts,

suicide attempts and suicide.

September 2000: During an FDA dermatology committee meeting, the

agency confirms that Accutane patients were linked to 147 suicides and

hospitalizations for depression from 1982 to May 2000 and says more

research is needed to assess the drug's risks of birth defects.

October 2000: The Archives of Dermatology publishes Roche-funded

research that studied 20,895 acne sufferers who took either Accutane

or antibiotics. The study found no link between Accutane and increased

risk of depression, suicide or other psychiatric disorders.

June 20, 2002: Accutane's label is changed to warn of " depression,

psychosis and, rarely, suicidal ideation, suicide attempts, suicide,

and aggressive and/or violent behaviors. "

September 2003: The Journal of the American Academy of Dermatology

publishes a Roche-funded study that found no significant increase in

prescriptions for antidepressants among patients already taking Accutane.

Nov. 18, 2004: FDA scientist David Graham tells Senate panel that the

drug should be studied for possible withdrawal.

Nov. 23: FDA announces registry of prescribers, patients and

pharmacies for Accutane, requires women test negative for pregnancy

before getting prescription.

 

Sources: FDA, Roche, USA TODAY research

 

For four months, the patients received either Accutane or an

antibiotic. New scans conducted on the group afterward showed the

Accutane patients had decreased activity in an area of the brain

thought to be involved with regulating mood.

 

" What we can say is that Accutane affects brain function ... and the

areas that are affected are the areas involved with depression, " said

Dr. J. Douglas Bremner, who led the research project at Emory

University Hospital in Atlanta.

 

Grant concedes that some might argue that his personal stake could

raise doubts about the integrity of the research. He said he tried to

guard against that by channeling the funding through the respective

universities involved and required that the study results be

published, " no matter what the outcome. "

 

" If you're a scientific researcher, you have a responsibility to do

the best work you can while being objective, " said Bremner. " In our

case, the study showed a change in brain function. That's not

something that's an interpretation one way or the other. "

 

Roche responds

 

Roche, however, questioned the studies and Grant's advocacy role in

funding them.

 

Commenting on McCaffery's research with mice, the company said: " It is

widely recognized that animal studies are not predictive of human

behavior as it relates to depression and suicide. "

 

Roche said there is no scientific unanimity that the area of the human

brain studied by Bremner definitely mediates depression. The company

also noted that Bremner's tests showed no differences in severity of

depression symptoms among the patients who received Accutane or an

antibiotic.

 

While noting that it's common for pharmaceutical companies to fund

drug research, Roche said, " It is quite another matter, in our view,

for a plaintiff in a lawsuit to fund a study to support his

allegations where there are no published studies that even suggest a

cause-and-effect relationship between Accutane and psychiatric events. "

 

Roche also cited three other scientific studies that showed Accutane

was not associated with increased risk for depression, other

psychiatric disorders or suicide. The studies, funded by Roche,

include one that found similar risk rates among more than 7,500 acne

patients who took Accutane and nearly 14,000 who took antibiotics.

 

Grant has cited the differing results of the studies he funded ­ along

with other scientific and legal information about Accutane ­ on a Web

site (www.accutaneaction.com) that features contributions by

individuals and families who say they have suffered serious medical

side effects from the drug. Their goal, stated on the Web site, is to

prompt a coordinated international investigation of Accutane.

 

" I don't let this take over my life, " said Grant, who explains that he

pursues his mission with the investigative approach he uses in his

accounting work. He even stopped reading letters from families whose

loved ones allegedly died or suffered other serious Accutane-related

side effects, " because it got to be too much emotionally. "

 

While preparing for next month's court hearing, however, he has kept

in touch with others fighting Accutane battles. One is Rep. Bart

Stupak, D-Mich., who is seeking a new congressional hearing on the

drug he blames for his own son's suicide. Grant has also spoken with

U.S. lawyers interested in any Irish court decision that could support

their own Accutane cases.

 

In a Sept. 7 letter, a Dublin law firm representing Roche and other

defendants said the group, though sympathetic about the death of

Grant's son, bore no " responsibility for his death. " But, even while

predicting that position would ultimately be vindicated in court, the

letter offered a settlement.

 

Under the deal, the defendants, including Roche, would pay the maximum

damages Grant would be entitled to under Irish law, plus related legal

costs. However, the letter stated the settlement would come " strictly

without any admission of liability. " Responding to questions from USA

TODAY, Roche said, " It made financial sense to offer to settle rather

than incur the costs of a protracted legal battle " because Ireland has

a statutory limit on awards in such cases.

 

Grant estimated any settlement could total nearly $1.5 million,

including the research costs ­ which Roche says it does not intend to

pay. But he rejected a deal, even knowing that defense attorneys would

likely seek a court-ordered end to the case on grounds he had turned

down everything he might ultimately win in court. " That's wrong, " says

Grant. " Because what I can get from a court is a ruling that Accutane

caused the death of my son and that Roche knew that the drug was a

serious risk. "

 

Even if the hearing goes his way, Grant faces at least a year of

additional legal procedures before a trial that could produce the

verdict he's seeking. He says he's determined to fight on, based on " a

conviction that I'm 100% correct. "

 

" The death of one person from this drug is too many, " Grant said.

" Somebody had to say stop. And that person happened to be me. "