Fwd: [SSRI-Research] Front Page! New York Times-Debate Resumes on the Safety of Depression's Wonder

[Guest guest]

Paxil and all of the SSRI type antidepressants cause a lot of problems, not just

suicide.

 

Others have associated this drug with violence, rage, etc.

 

Disturbed cognitive thinking. Brain Damage. Other things. Watch out.

 

We have been trying to tell people about these drugs since the inception of this

group, almost 2 years now. We have people in this group who are on these type

of drugs. If you have been reading these messages and continue not to really

learn about them, you cannot say we didn't warn you.

 

Frank

 

JustSayNO wrote:

 

JustSayNO

Thu, 07 Aug 2003 22:28:02 -0000

[sSRI-Research] Front Page! New York Times- " Debate Resumes on the

Safety of Depression's Wonder

 

August 7, 2003

 

Debate Resumes on the Safety of Depression's Wonder Drugs

By GARDINER HARRIS

http://www.nytimes.com/2003/08/07/health/07DEPR.html?8hpib

 

Warnings by drug regulators about the safety of Paxil, one of the

world's most prescribed antidepressants, are reopening

seemingly settled questions about a whole class of drugs that

also includes Prozac and Zoloft.

 

Doctors are just beginning to react to the finding — reported first

by British drug authorities in June and then endorsed the next

week by the Food and Drug Administration — that unpublished

studies about Paxil show that it carries a substantial risk of

prompting teenagers and children to consider suicide.

 

Because the studies also found that Paxil was no more effective

than a placebo in treating young people's depression, the

regulators recommended that doctors write no new Paxil

prescriptions for patients under 18. Experts say that the suicide

risk is highest in the first few weeks young patients are on the

drug.

 

The concern that Paxil and drugs like it could cause suicide had

been weighed, and rejected, by regulators a dozen years ago,

amid early concerns about the group of antidepressants known

as selective serotonin reuptake inhibitors, or S.S.R.I.'s. In the

meantime, millions of people have taken the drugs, and many

experts say that they have prevented far more suicides by

teenagers and children than any reading of the new findings

suggests they could have caused.

 

Almost no one suggests that Prozac, Zoloft, Paxil and their

cousins are not safe for the vast majority of adults, although

studies have shown them to be only modestly effective.

 

Still, the warnings have the early critics saying they feel

vindicated. Plaintiffs' lawyers who have uncovered evidence that

they say shows drug makers withheld evidence of the S.S.R.I.'s

suicide risk from regulators say the warnings give fresh urgency

to their claims.

 

And the findings have unsettled some of the very experts who

absolved S.S.R.I.'s of a link to suicide a dozen years ago. Of the

10 American specialists who, as members of an ad hoc F.D.A.

panel, formally cleared the drugs of a link to suicide in 1991,

seven now say that the new information would prompt them to

reconsider that decision, if they were asked.

 

" In 1991, we said there wasn't sufficient evidence to support a

link between these drugs and suicide, " said Dr. Jeffrey A.

Lieberman, a professor of psychiatry and pharmacology at the

University of North Carolina and a member of the panel. " Now

there is evidence, at least in children, and I wouldn't rule out that

it's in adults, too. "

 

British health authorities have promised to " urgently " examine

the implications of their findings for adults. The F.D.A. is

considering whether to impose new restrictions on the use of

the antidepressants. The agency's warning emphasized that

younger patients " should not discontinue use of Paxil without

first consulting their physicians, " adding, " it is important that Paxil

not be abruptly discontinued. "

 

While the regulators' warnings address only Paxil, many of the

experts on the 1991 panel said all S.S.R.I.'s act similarly in the

body, so concerns about one could apply to all.

 

The drugs' manufacturers, which sell billions of dollars of

S.S.R.I.'s every year, have treaded carefully in responding to the

warnings. Without criticizing the regulators, they maintain that

there is no proof that their drugs have a link to suicidal thinking in

young patients — and they point out that the F.D.A. in the past

found no merit in such claims.

 

" We're trying right now to look at this issue with the F.D.A. and

come up with an understanding together of what the data mean, "

said Dr. Philip Perera, a medical director of GlaxoSmithKline, the

British company that makes Paxil. Pfizer, the maker of Zoloft,

said that its drug was different from Paxil and had passed all

F.D.A. safety evaluations, including one as recently as June 12.

Eli Lilly & Company said that Prozac does not cause suicides.

 

So far, there is little evidence that the warnings have affected

doctors' prescribing practices. Teenagers and children account

for about 5 percent of S.S.R.I. prescriptions, and companies that

track the industry have detected no falloff in sales.

 

" I can hardly imagine working without these drugs, " said Dr.

William Schreiber, a Louisville, Ky., internist. " These are good

drugs, and I think they're safe drugs. "

 

But the warnings are beginning to seep into doctors' awareness.

Connecticut officials, for example, last month dropped Paxil from

their list of approved medications for foster children. And even

doctors who do not believe there is a link between S.S.R.I.'s and

an increased risk of suicide are emphasizing that patients need

to be closely monitored in their first weeks on the drugs.

 

" See them every day, if you need to, " Dr. Perera of

GlaxoSmithKline said.

 

The drugs are widely prescribed by general practitioners, who do

not have the same training in depression and treatment as

psychiatrists.

 

With S.S.R.I.'s now the most prescribed drugs for depression, it

is easy to forget how high passions ran when the F.D.A.

convened an expert panel in 1991 to weigh claims that Prozac

and other S.S.R.I.'s may cause some patients to become

suicidal. The panel's hearing in Bethesda, Md., was mobbed; its

chairman wore a bulletproof vest.

 

Dozens of people told stories like the one related by Melinda

Harris. Blaming Prozac, she described how her father came into

the kitchen one morning, picked up a 12-inch butcher knife and

stabbed himself repeatedly in the stomach.

 

Just as emotionally, advocates for the mentally ill pleaded with

the panel to reassure patients that they could take Prozac with

confidence. Representatives of Eli Lilly cited studies finding no

connection between suicide and the drug, which had been on

the market for almost four years.

 

Despite the sharp conflict, the panel voted unanimously in

Prozac's favor, and the controversy died down. To this day, the

panel's findings are cited to rebut claims that the drugs can be

harmful.

 

But some of the early critics say the warnings demonstrate their

prescience. " I feel vindicated, " said Joseph Glenmullen, author

of " Prozac Backlash, " a fierce critique of antidepressants. " These

companies have vehemently denied this side effect for over a

decade, and now their own data indicate there's a significant

risk. "

 

The British regulators said that their analysis of the nine studies

of Paxil found 3.2 times the likelihood of suicidal thoughts or

suicide attempts among teens and children given the drug as

among patients given a placebo. They also said that Paxil has

not proved effective against depression in children and

teenagers.

 

Some experts suspect that in the first few weeks of therapy,

drugs like Paxil can shove a small number of patients toward a

mental precipice, perhaps because they can cause a severe

form of restlessness known as akathisia. Patients who make it

through the first weeks of drug therapy uneventfully do fine on the

medication on the long term, these experts say.

 

Teenagers and children seem particularly vulnerable, said Dr.

Mark A. Riddle, director of the division of child and adolescent

psychiatry at the Johns Hopkins Children's Center.

 

" Kids tend to get quite activated, especially on adult doses of

S.S.R.I.'s, " said Dr. Riddle, who in 1991 conducted one of the

first studies of the drugs in younger patients. " We had a lot of

cases of kids who became so disinhibited they did reckless

things, " he said, describing those early findings.

 

In recent years, most debate among doctors and researchers

about the S.S.R.I.'s has focused on whether they are effective,

rather than whether they are safe.

 

Dr. David Shaffer, a researcher at Columbia University, noted

that teenage suicides have fallen significantly in every country

where Prozac and its cousins are in widespread use.

 

" This amazing, undreamt of and unhoped for reduction in suicide

rates is probably the result of more liberal treatment of young

people with S.S.R.I.'s, and it's suggestive that these drugs may

be responsible for saving a lot of lives, " Dr. Shaffer said. " The

introduction of S.S.R.I.'s has been a revolution. "

 

Yet most studies — including those recently reviewed by British

and American health regulators — have found that S.S.R.I.'s are

no more effective in fighting teenage depression than sugar

pills.

 

Even in adults, S.S.R.I.'s have been found to offer only modest

benefits. In about half of all adult tests, the drugs prove no more

effective than placebos. On average, they reduce symptoms of

depression by about 41 percent on a widely used scale, versus

a 31 percent reduction among those taking placebos, according

to a survey in 2000 of studies used by the F.D.A. in approving the

drugs.

 

Researchers, moreover, have not been able to analyze much of

the data on the drugs, because they have not been made public.

 

GlaxoSmithKline, for instance, has acknowledged that just one

of its nine studies of Paxil in children and adolescents has been

published — a study that made only passing mention of suicide

and concluded that the drug was effective against depression.

According to the F.D.A., the combined results of all nine trials

show that the drug is not effective against depression in patients

under 18. Of the S.S.R.I.'s, only Prozac is approved by the F.D.A.

to treat depression in children and teenagers, although doctors

also widely prescribe the others.

 

Dr. Graham Emslie, a professor of psychiatry at the University of

Texas Southwestern Medical Center who was a researcher in

four of GlaxoSmithKline's studies of Paxil, said he suspected

that the other studies went unpublished at least in part because

the results were unfavorable.

 

" Some of these studies were finished a couple of years ago, " Dr.

Emslie said. " But negative trials tend not to get published. "

 

Dr. Perera, the GlaxoSmithKline official, said that publishing

studies " takes time. " He declined to say if the company would

seek to publish the eight Paxil studies that have not appeared in

journals.

 

According to Dr. Emslie, other companies have withheld

negative studies of S.S.R.I.'s. " I know of at least a half-dozen

other studies of antidepressant treatments in children and

adolescents that have been completed but as yet have not been

published, " he said. " More than enough time has passed for

these to be published at least in abstract form. " He refused to

identify the companies or the drugs involved because he, like

other researchers involved in similar research, has signed

contracts promising secrecy.

 

With negative results not disclosed, researchers and physicians

often believe that drugs are more effective and safer than they

actually are, according to Dr. Marcia Angell, a former editor of The

New England Journal of Medicine. " It changes the way medicine

is practiced, " Dr. Angell said.

 

Back in 1991, in their presentation to the blue-ribbon committee

reviewing Prozac, Lilly scientists made much of the fact that

studies analyzing Zoloft and Paxil failed to show any link

between those drugs and an increase in suicides.

 

" There is simply no scientific evidence whatsoever, no

placebo-controlled double-blind study, that has established a

cause-and-effect relationship between antidepressant

pharmacotherapy of any class and suicidal acts or ideation, "

said Dr. Charles B. Nemeroff, a professor of psychiatry at Emory

University who worked as a consultant and spoke on behalf of

Lilly.

 

In an interview, Dr. Nemeroff said he believed that his statement

was accurate then and remains so, since he has not seen any

published study to contradict it.

 

The British and American regulators have reached a different

conclusion. And experts hired by lawyers suing the

manufacturers over claims that the drugs led to suicides

question whether the F.D.A. received a full picture of the available

research in 1991.

 

For instance, F.D.A. procedures required Lilly to inform the

agency of any concerns about Prozac raised by other national

health authorities. But court records show that Lilly never told the

F.D.A. or the expert panel that German regulators initially refused

to approve Prozac's sale in 1985 because of concerns over a link

with suicide.

 

In their analysis of Lilly's data, the German authorities said that

Prozac seemed to have caused a substantial increase in suicide

among users, according to court records. Ultimately, the

Germans approved Prozac with a warning that physicians

should consider using sedatives for patients at risk of suicide.

 

No such warning is included in Prozac's label in the United

States, although the risk of suicidal thinking is listed among the

drug's side effects.

 

Gary Tollefson, a Lilly executive who spoke before the 1991

panel, was asked in a deposition why he did not tell the experts

about the German concerns.

 

" That was not a question I was asked, " he said, according to

court records, " so I did not answer that question. "

 

Documents brought to light in other cases suggest that Lilly

struggled for years to reconcile suicidal events among patients

taking Prozac in its trials. One memo shows that a top Lilly

executive asked the company's own researchers to record

suicide attempts as " overdose " and thoughts of suicide as

" depression. "

 

In another memo, a Lilly employee objected to those

instructions, making reference to the German health authority,

known by its initials as the B.G.A. " I do not think I could explain to

the B.G.A., a judge, to a reporter or even to my family why we

would do this especially on the sensitive issue of suicide and

suicidal ideation, " he wrote.

 

In a recent statement, Lilly said: " There is no credible scientific

evidence that establishes a causal connection between Prozac

and violent or suicidal behavior. To the contrary, scientific

evidence shows that Prozac and other antidepressant

medications appear to reduce these behaviors. "

 

Lilly representatives told the 1991 panel that the company had

put together a series of proposed studies to examine the suicide

issue and said one of the studies had already been started.

According to plaintiffs' lawyers, Lilly never completed the study;

Lilly declined to comment.

 

Were the F.D.A. to reconstitute the 1991 panel, its members

would again be presented with a confusing mix of data on the

issue — despite the passage of 16 years since Prozac's

introduction and the use by tens of millions of people of it and

other S.S.R.I.'s.

 

Under the circumstances, one member of the panel, Dr.

Keh-Ming Lin, a professor of psychiatry at the University of

California at Los Angeles, said the new information unearthed by

regulators might lead him to change his vote absolving S.S.R.I.'s

of suicide risk.

 

" If you have data that's worrisome, you tend to be conservative, "

Dr. Lin said, " even when the question isn't resolved. "

 

Copyright 2003 The New York Times Company