FDA Requests Anticonvulsant Suicide Data Analysis - Boston Globe

[Guest guest]

SSRI-Research@

Fri, 29 Apr 2005 01:17:07 -0400

[sSRI-Research] FDA Requests Anticonvulsant Suicide Data

Analysis - Boston Globe

 

 

 

 

FDA Requests Anticonvulsant Suicide Data Analysis - Boston Globe

 

Wed, 20 Apr 2005

 

http://www.ahrp.org/infomail/05/04/20.php

 

Thanks to the persistent advocacy efforts of attorney, Andrew

Finkelstein, the FDA has finally sent letters to 14 manufacturers of

anticonvulsant drugs, such as Pfizer's Neurontin, to examine the

suicide data from these drugs.

 

Finkelstein began his campaign to get the FDA to issue Black Box

warnings about the suicide risk posed by Neurontin, whose sales

reached $2.6 billion with 17 million prescriptions. When he first

contacted the FDA in March 2004, he had evidence that more than 100

people prescribed Neurontin had committed suicide and 2,000 had

attempted suicide.

 

The current drug label includes a brief warning that " suicide gesture "

was a rare adverse event observed in clinical trials. Finkelstein then

filed a citizen's petition (776K pdf file) with the FDA in May 2004,

at which point the suicide death toll had reached 160. The petition

asked that the agency require Pfizer to include a Black Box warning on

the Neurontin label.

 

By March 2005, the death toll from suicides in patients prescribed

Neurontin had reached 258. See:

http://www.ahrp.org/risks/neurontinSuicide0305.pdf

 

Today's Boston Globe reports that Finkelstein has evidence that

Neurontin-linked suicide death toll has reached 271. With the rapid

increase in suicides by patients prescribed Neurontin, why has the FDA

failed to issue a public advisory?

 

Dr. Robert Temple, FDA's associate director for medical policy for the

Center for Drug Evaluation and Research, is quoted saying:

 

" If it's important and has some credibility then we do it. But at the

moment the public is saying we want to know what [the FDA's] concerns

are even if it goes away and it's a false alarm. "

 

False alarm??

 

That's what the FDA's rationale when it brushed aside the

Prozac-related suicides in 1991 and during the intervening years.

 

Dr. Temple, a rapid increase in suicide fatalities is not a false alarm.

 

Would an official of the Federal Aviation Administration call 271

deaths occurring in passengers on one particular airline--a false alarm?

 

Contact: Vera Hassner Sharav

212-595-8974

 

 

THE BOSTON GLOBE

FDA requests anticonvulsants be reexamined

By Liz Kowalczyk, Globe Staff

April 20, 2005

 

The Food and Drug Administration has asked the makers of epilepsy

drugs, which are the fifth best-selling group of medications and are

taken by millions of Americans, to reexamine their data to determine

if the drugs increase patients' risk of suicide.

 

The agency has requested an analysis similar to the one it

commissioned to evaluate whether antidepressants pose a similar risk

to children and teenagers. That sweeping reexamination of clinical

trial data found that antidepressants can increase suicidal thoughts

and behavior in young people, and last year the FDA required

manufacturers to include a stronger, more prominent warning, known as

a " black box, " on the drugs' labels.

 

The agency, which has been the target of growing criticism from

members of Congress over how it monitors drug safety, is under

pressure to more carefully scrutinize anticonvulsants, particularly

Neurontin, which is made by Pfizer Inc. and is the market leader.

 

A year and a half ago, a New York attorney, Andrew Finkelstein, who

has handled thousands of personal injury cases, bought a 15-second

national television spot searching for patients who had attempted or

committed suicide while taking Neurontin. He said he got the idea from

a client who had attempted suicide while taking the drug for bipolar

disorder.

 

In May 2004 he filed a citizens petition with the FDA, asking that the

agency require Pfizer to include a black box warning on the drug's

label. The current drug label includes a brief warning that " suicide

gesture " was a rare adverse event observed in clinical trials.

 

So far, Finkelstein said, he has submitted 271 " adverse event " reports

to the FDA describing patients who have killed themselves while taking

the drug, and he has filed more than 70 personal injury lawsuits

against Pfizer, none of which have been settled or tried.

 

In a letter to Finkelstein last week, an FDA official said the agency

is " taking this matter very seriously " and has told drug makers to

reanalyze their clinical trial data. The letter was written by Dr.

Russell Katz, director of the Division of Neuropharmacological Drug

Products, who said the agency also is reviewing Finkelstein's citizens

petition.

 

Pfizer executives said yesterday that the clinical trial data it has

submitted to the FDA in the past refutes any connection between

Neurontin and suicide, and that it cooperates with all FDA requests.

Executives at two other companies that make anticonvulsants said they

are cooperating with the FDA's request.

 

In an interview this week, Dr. Robert Temple, associate director for

medical policy for the FDA's Center for Drug Evaluation and Research,

confirmed the agency's request but stressed that officials do not have

" any preconceptions " about what conclusions they will reach. The FDA

sent letters to 14 manufacturers for data. Drug makers conduct

clinical trials before asking the FDA to approve their drugs, testing

the medicines in patients, and collecting data on whether they work

and have side effects.

 

Temple said that this particular analysis is complicated because

doctors prescribe anticonvulsants for many conditions and illnesses

besides epilepsy, including pain, migraines, insomnia, and bipolar

disorder, contributing to their soaring use. Some of these illnesses,

particularly bipolar disorder, carry a risk of suicide themselves.

 

" These are the sorts of people who are complicated to think about

because they tend to be at risk already, " he said. " There's a 10 to 20

percent incidence of suicide in bipolar disorder. " The adverse event

reports " can't really tell you whether the suicidal event is because

of the drug or despite the drug, " he said.

 

But this also was true of depressed young people who were taking

antidepressants, and the agency eventually was able to uncover a

connection between the drugs and increased risk of suicidal thoughts

and behavior. The agency now is analyzing whether antidepressants can

increase the risk of suicide in adults.

 

Neurontin is the best-selling anticonvulsant in the United States.

Pfizer's Neurontin sales were more than $2.6 billion last year, as

doctors wrote 17 million prescriptions, according to IMS Health, a

Connecticut pharmaceutical information and consulting company.

 

A year ago, the company's Warner-Lambert division pled guilty to

criminal conduct and paid $430 million in fines to resolve charges

that it illegally marketed Neurontin for illnesses ranging from

migraines to hiccups.

 

Companies are not allowed to market drugs for unapproved uses,

although doctors are free to prescribe them.

 

Mary Anne Rhyne, spokeswoman for GlaxoSmithKline, the maker of

Lamictal, another anticonvulsant, said the company is working on the

FDA's request, which it received in March, and must reach an agreement

with the agency on which clinical trials to include in the analysis.

Once that's done, the FDA has given the company six months to complete

the reexamination. Rhyne said the company previously found no

increased risk of suicide among bipolar patients taking Lamictal,

which is approved for that disorder.

 

Lesley Fishman, a spokeswoman for Ortho-McNeil, which makes the

anticonvulsant Topamax, said: " We have received a request and we are

complying with this data request. " She declined to provide further

details.

 

Finkelstein said the FDA is not acting fast enough and that patients

are in danger.

 

He has asked the FDA to issue a Public Health Advisory to doctors and

patients while the agency's review is underway, alerting them to the

potential connection between Neurontin and suicide, and advising them

to monitor patients carefully for deepening depression and suicidal

thoughts. The agency issued such an advisory when it was reviewing the

connection between certain antidepressants and suicidal behavior in

children, he said.

 

" Why keep this review a secret? " Finkelstein asked.

 

Temple declined to comment on whether the FDA plans to issue a Public

Health Advisory, and said the agency agonizes about these decisions.

 

" If it's important and has some credibility then we do it. But at the

moment the public is saying we want to know what [the FDA's] concerns

are even if it goes away and it's a false alarm, " he said.

 

Temple said that one reason for reanalyzing the data is that a

particular risk could be hidden because it is not clearly labeled. For

example, he said, antidepressant makers sometimes classified suicidal

thinking as " emotional liability, " with the result that the prevalence

of suicidal behavior could have been understated.

 

Companies also collect ongoing clinical trial data after a drug is

approved.

 

Dr. Roy Perlis, a psychiatrist at Massachusetts General Hospital, said

it is also crucial to consider a drug's benefits to patients, which

may outweigh the risks. In the case of antidepressants and children,

he said, one major factor was that the drugs did not show a clear

benefit for depressed children.

 

Dr. Joseph Glenmullen, a Cambridge psychiatrist who has written

several books about antidepressants, said that when a rapidly growing

number of people take a drug or a class of drugs, as has happened with

anticonvulsants, little-noticed side effects can become more

prevalent. " There has been an ongoing debate for a long time about

antidepressants and suicide, but anticonvulsants are a whole new

area, " he said.

 

© Copyright 2005 The New York Times Company

 

FAIR USE NOTICE: This may contain copyrighted (© ) material the use of

which has not always been specifically authorized by the copyright

owner. Such material is made available for educational purposes, to

advance understanding of human rights, democracy, scientific, moral,

ethical, and social justice issues, etc. It is believed that this

constitutes a 'fair use' of any such copyrighted material as provided

for in Title 17 U.S.C. section 107 of the US Copyright Law. This

material is distributed without profit.