2,300 families blame the drug Neurontin for suicide or suicide attempts

[Guest guest]

This is just a very small tip of the iceburg. Many millions are

damaged each year by drugs and almost all are " not reported " .

 

 

 

" Zeus " <info

 

2,300 families blame the drug Neurontin for suicide or

suicide attempts

Tue, 3 May 2005 22:06:00 +0100

 

 

2,300 families blame the drug Neurontin for a suicide or suicide

attempt and are taking legal steps against its maker, Pfizer Inc.

 

Rick Crone was the rock in his family.

 

The Marine veteran -- and father of two -- handled much of the care of

his disabled wife, Nicolette, for the more than two decades they were

together.

 

But in 2001, Rick's spirits plummeted, an ominous change Nicolette

said she first noticed after he started taking a new prescription for

back pain. His upbeat personality faded over the next months, and late

one night in April 2002 as his family slept, the 49-year-old father

walked into the garage and hanged himself.

 

Unknown to the family in Clearlake (Lake County), Nicolette Crone

later said, was that the medicine, Neurontin, was an epilepsy drug. It

had been prescribed to Rick " off label " because treating back pain was

not a use approved by the Food and Drug Administration.

 

She now is among 2,300 families who blame Neurontin for a suicide or

suicide attempt and are taking legal steps against its maker, Pfizer Inc.

 

And she is part of a growing chorus saying that patients should be

told when a treatment has not been through the FDA's rigorous approval

process. No law requires doctors to disclose to their patients that

they are prescribing a drug for an off-label use.

 

Pfizer, which sold $2.7 billion worth of Neurontin last year, denies

that the drug caused suicides, stating that comprehensive data over

the past decade " refute any suggestion that Neurontin causes

depression, suicidal thoughts or suicidal behavior. "

 

The FDA, however, recently asked Pfizer and 13 other manufacturers to

look for signs of suicide risks in data on Neurontin and other drugs

for epilepsy.

 

In addition to epilepsy, Neurontin is approved to treat pain from a

skin ailment known as shingles. But the vast majority of Neurontin's

prescriptions are for off-label uses, such as bipolar disorder and --

as was Rick Crone's case -- back pain.

 

Off-label prescriptions are legal and common, encompassing a wide

range of drugs, from skin creams to anti-depressants to cancer

therapies. A 1992 American Medical Association study estimated that 40

to 60 percent of prescription drugs were given for unapproved uses.

 

Although off-label uses can be valuable, even lifesaving, some are

backed only by flimsy studies. In other cases, off-label treatments

once favored by doctors have later proved to be harmful, even deadly.

 

Many patients, however, aren't aware of this. While most states

require doctors to obtain informed consent for medical treatment, no

law gives patients the right to know when they're given an off-label

treatment.

 

Whether doctors should make that disclosure is a question relevant to

all patients, because off-label prescriptions are so widespread.

Billions of dollars are spent every year on these treatments that

drugmakers and many doctors praise as innovative medicine, but critics

liken to experiments on unwitting guinea pigs.

 

The real impact on individual patients can be hard to gauge, because

the treatments are tried outside the controlled conditions of clinical

trials.

 

Rick Crone's doctors had him on other painkillers besides Neurontin --

not unusual in the treatment of back pain. His wife, alarmed by his

slide into depression, had urged him to get his prescriptions reduced.

 

His death left Nicolette Crone, 45, grief-stricken and struggling to

cope as a single mother who uses a wheelchair because of injuries in

her youth. She's also dealing with her children's pain. Rick Crone's

body was found by the child he called his " little angel,'' his

daughter, Cassie, then 13. Hearing her cries, Rick's 16-year-old son,

Ben, rushed in and desperately tried to save his dad.

 

Whatever level of suicide risk, if any, the FDA finds for Neurontin,

millions more people will have been exposed to that risk than the

relatively small number of patients who received it for its two

approved conditions.

 

Whether those patients who took it off label -- for ailments including

migraine headaches, psychiatric illnesses and restless leg syndrome --

received any benefits while bearing Neurontin's risks is open to

debate because the drug was never evaluated by the FDA for those uses.

 

And whether the benefit outweighed the risk also is in question. A

patient trying to control seizures might be willing to accept fairly

serious side effects, but someone taking the same drug for a headache

or back pain might find those risks unacceptable.

 

Like many family members who are now raising questions about off-label

treatments, Nicolette Crone believes patients deserve to know when

their prescriptions are not for FDA-approved uses.

 

" Why didn't they tell us?'' she said. " One person's life affects so

many others.''

 

Armed with the knowledge that a prescription was off label, proponents

say, patients might ask more questions; seek other sources of

information, such as the Web; watch more closely for side effects; or

ask for an approved treatment instead.

 

But doctors say such a disclosure would only scare patients, possibly

spurring them to refuse a medicine they sorely need.

 

Faith in the sober judgment of physicians, however, has been shaken by

recent revelations of illicit drug industry tactics to influence

doctors and distort the scientific evidence available to them about

off-label uses.

 

Federal prosecutors charged last year that Neurontin's multibillion-

dollar market arose from illegal strategies such as paying doctors to

promote it off label for dozens of conditions, from back pain to

psychiatric illnesses. The case was settled with a $430 million fine

and guilty pleas by a Pfizer unit.

 

Another drugmaker, GlaxoSmithKline, was accused last year of burying

studies on its anti-depressant Paxil while encouraging doctors to

prescribe it off label to children. The studies indicated the drug

didn't work well in adolescents and might be linked to cases of suicide.

 

Lawyers representing thousands of families in personal injury cases

involving Neurontin, or anti-depressants such as Paxil, say none of

their clients were told the drugs were given off label.

 

If doctors don't voluntarily reveal when their prescriptions are off

label, patients can always bring up the issue. But it's not a question

many people would think to ask.

 

A 2004 poll commissioned by a division of the Wall Street Journal

suggests that most Americans are assuming every prescription is

FDA-approved. More than half the 2,148 people surveyed said they

didn't even know off-label prescribing was legal. Another 17 percent

weren't sure.

 

In fact, once a drug is FDA-approved for even a single disease, it can

be legally prescribed for any other ailment. Although the FDA can

distribute advisories to doctors and issue warnings of drug side

effects, it does not directly regulate the practice of medicine -- a

role filled by state governments.

 

The FDA does, however, forbid most promotion of off-label uses by drug

manufacturers until they conduct studies to support the agency's

approval for that new use.

 

Off-label treatments not only include prescribing a drug for a new

disease, but also significantly changing the dose, combining it with

other treatments, or using the drug in a new population, like

children, not named on the original FDA label.

 

Mainstream physician groups such as the American Medical Association

say off-label treatments sometimes provide the best possible care. For

example, the well-known antiviral drug AZT, originally a cancer

treatment, was used off label for a time before it was approved to

delay the onset of AIDS in HIV- infected people. Many doctors also

point to the beta blockers, medicines approved to lower blood pressure

that also were used to decrease the risk of death after a heart attack.

 

Some off-label treatments, however, have been linked to deaths or

severe side effects, like the heart valve damage caused by the

diet-drug regimen known as fen-phen. Hormone replacement therapy, a

menopause treatment, was once prescribed to millions of women in the

belief it would ward off cancer and stroke. Major studies have since

found the drugs actually increase those risks.

 

The range of risks and benefits with off-label treatments, though not

clearly known, probably varies widely. Some unapproved uses may be

backed only by inconclusive studies, while others are supported by

high-quality research.

 

Arthur Levin, executive director of the Center for Medical Consumers

in New York, said patients cannot give truly informed consent to

medical treatment without knowing when a therapy is off label.

 

" If it's not an approved use, they're taking it experimentally,''

Levin said. " They should know that, and decide whether they want to

participate.''

 

If Rick Crone had been a participant in a formal research trial on the

effect of Neurontin for back pain, the scientific investigators would

have been required by federal statutes to inform him that the

treatment was experimental and obtain his consent in writing.

 

But when the same drug is prescribed off label in ordinary medical

practice, the requirements for patient consent -- governed by state

laws -- are far less stringent.

 

In California, physicians don't always need written consent, but they

must outline the benefits and potential risks of the drug. State law

also generally requires doctors to disclose other information they

think a reasonably prudent patient would need to make an informed

decision.

 

But whether that means a doctor is obliged to reveal a proposed

treatment's off-label status would depend on the particular facts in

that case. A jury in a malpractice suit might decide either way, said

Hans Lee, a staff attorney for the California Medical Association.

 

One Oakland woman thinks the law needs to change. After Maddy Oden's

32- year-old daughter, Tatia, died in 2001 during labor induced by an

unapproved treatment, she became an advocate for hard-and-fast

government rules requiring doctors to tell patients every time they

prescribe off label.

 

Oden found out to her dismay that doctors continue to use the ulcer

drug Cytotec off label to induce labor, in spite of a 2000 warning by

the drugmaker that Cytotec could cause a pregnant woman's uterus to

rupture. Doctors maintain the drug can be used safely with careful

monitoring.

 

A visit from Oden spurred California Assemblywoman Loni Hancock late

last year to consider framing a state law that would make off-label

disclosure by doctors mandatory.

 

" I would want to know it,'' Hancock, D-Berkeley, said at the time. " It

would lead me to ask other clarifying questions. For example: Is there

another drug that is approved for this use or this population, like

children? What evidence is there that this off-label drug is better,

or that it's safe?''

 

Hancock's office began by focusing on rules for the off-label use of

Cytotec and found conflicting opinions among doctors and women's

groups. No bill is on the table, but Hancock said she will continue to

work on the issue.

 

Physicians who believe strongly in giving their patients full

briefings about a drug's known benefits and risks may nevertheless

quail at the idea of telling them the treatment is off label. The

reason often given: fear of scaring patients away from a remedy the

doctor believes could be the best possible alternative.

 

This reluctance can be found even among doctors credited with helping

prevent injuries from off-label uses.

 

Dr. Raymond Woosley, a University of Arizona pharmacology expert, took

part in renowned clinical studies in the late 1980s that proved two

heart drugs promoted for off-label use actually increased the risk of

death.

 

But Woosley doesn't see an advantage in doctors discussing a

treatment's off-label status with patients. The off-label use may lack

FDA approval for any of a variety of reasons unknown to the doctor, he

said -- perhaps because the company simply couldn't afford to apply

for an expanded FDA approval.

 

" Doctors can't manage that information, and patients can't either,''

he said. " A patient may refuse a drug that could be very valuable.''

 

A spokesman for the international trade association for biotechnology

firms, the Biotechnology Industry Organization, said an off-label

disclosure law would hamstring doctors, harm patients and sink biotech

firm revenues.

 

" We have a lot of products that are cancer products, and a majority of

their use is off label, " said Jayson Slotnik, the biotech

organization's director of Medicare reimbursement and economic policy.

He said a disclosure law would make doctors hesitant to use

non-FDA-approved treatments.

 

The major trade association representing large drugmakers, the

Pharmaceutical Research and Manufacturers of America, said such

legislation might be consistent with the group's policies promoting

patient awareness, depending on how the law was implemented.

 

A prominent industry lawyer maintains that doctors should have no

obligation to disclose off-label status because it is irrelevant in

their discussions with patients. Off label doesn't automatically

signal a higher level of risk, said James Beck, who wrote an

influential 1998 law review article on the issue. Beck argues that

off-label treatments include those that are widely accepted as the

standard of care. At the same time, some drugs prescribed for

FDA-approved uses have later been found to cause unforeseen harm.

 

" All medical treatments, including off-label treatments, have medical

risks, and patients must be informed of medical risks,'' Beck wrote.

 

Consumer advocates and drug regulators, on the other hand, say doctors

may be hard-pressed to inform their patients of the risks of

treatments never reviewed by FDA standards. The thorough studies that

might identify those risks, in a new patient population with a

different disorder, often have not been conducted, they say.

 

A prime example is the state of knowledge about adult drugs used off

label in children, said Dr. Dianne Murphy, director of the FDA's

pediatric drug development office. Awareness began growing in the

1960s that the results of adult studies do not necessarily predict how

the developing bodies of children would react to drugs, Murphy said.

 

" I think it's really wrong to say you have the same level of knowledge

for a product being used off label than ones that have been

approved,'' Murphy said.

 

Some parents, unaware their children were given unapproved treatments,

are now haunted by questions they didn't know to ask. Parents would

rather learn up front about all possible risk factors than anguish

over their decisions later, one father said.

 

Jay Baadsgaard, a Washington state farm employee, now spends hours on

the Internet researching the anti-depressants his 15-year-old son was

taking off label in 2001 when he brandished a hunting rifle during

class. Fortunately, the boy didn't shoot anyone.

 

Baadsgaard supports mandatory disclosure when a prescription is off label.

 

But Baadsgaard said people don't have to wait for a change in the law

to get fuller information from the doctor -- including the FDA status

of a drug.

 

" We have to remember he's working for us, and we can ask him any

question we want,'' Baadsgaard said. " If we don't get the answer, we

can get up and leave.''

What does 'off label' mean?

 

" Off label'' is a shorthand term for a drug or medical procedure that

is prescribed for a use other than the approved use on its Food and

Drug Administration label. For example, a doctor might prescribe a

drug approved to treat one disease, like cancer, as a remedy for

another condition, like psoriasis. Or a drug approved in adults might

be prescribed off label for children. A change in an approved drug

dose, or a surgical procedure that is modified, can also be an

off-label use.

Ask your doctor

 

Off-label prescriptions are widespread, encompassing a vast spectrum

of medicines. Such drugs are sometimes the best treatment available.

In other instances, they have been linked to severe side effects. If

you're not sure whether the drug you've been prescribed is off label

or not, ask your doctor. If it is, here are some more specific

questions you could ask (but bear in mind these aren't the typical

questions that physicians hear).

 

-- Has the FDA approved this treatment for people with my condition?

For my age group? At this dosage level? For this duration of time?

 

-- What sources of information did you draw on to decide that this was

right for me?

 

-- What are the benefits and risks, and how can they be known without

FDA evaluation? Does the off-label treatment have dangerous

interactions with other remedies used for my condition?

 

-- Are there alternative treatments for my condition that are FDA-

approved? What are their benefits and risks?

The lowdown on off-label treatments

 

What are the limitations on off-label drugs?

 

Once a drug has FDA marketing approval for at least one ailment, it

can be legally prescribed for any other disease. However, doctors are

expected to choose these treatments based on sound evidence. If they

do not, they may be vulnerable to malpractice suits.

 

Drug companies are generally forbidden from promoting their products

for off-label use. They can earn the right to advertise drugs for

additional uses if they submit studies to the FDA proving that the new

use is safe and effective.

 

How prevalent are off-label drug prescriptions?

 

Estimates of the size of the off-label drug market range from 20 to 60

percent of the nation's $235 billion annual prescription-drug bill.

Off-label use is highest in certain fields like oncology. Doctors

often try unapproved remedies against life-threatening diseases like

cancer when approved therapies are no longer effective.

 

Why are off-label drug prescriptions so common?

 

The FDA does not require manufacturers to obtain approval for all

conditions where a drug may have some value. The approval process is

expensive, and a drugmaker may decide to forego it when, for example,

the new use would bring in just a few extra customers afflicted with a

rare condition. In addition, most drugs are tested only in adults to

obtain approval. Therefore, the majority of drugs given to children

are off label in that population.

 

Beyond that, prosecutors have accused some drug firms of drumming up

huge off-label sales through illegal promotion.

 

For patients, what are the benefits of off-label drugs?

 

A use unapproved by the FDA may nevertheless be regarded by doctors as

effective. Doctors base these judgments on their own clinical

experience, the opinions of their colleagues, published studies and

information from drug company sales representatives. Patients may

benefit from the early use of a drug that is expected to win FDA

approval soon for a new use that is supported by high-quality research.

 

The actual benefits of many off-label drugs, however, may never be

known unless the manufacturer or outside researchers conduct

well-designed clinical trials like those required by the FDA. Some

medical studies relied on by physicians are too small or too badly

designed to prove that a use is effective.

 

What are the risks?

 

As with the benefits, the risks of off-label drugs may be largely

unknown. Factors that are considered in depth when the FDA approves a

drug for its original indication may never be systematically studied

for an off-label use. These factors include the appropriate dose to

treat the new disease; the possible side effects for people with

different health problems; and any potentially dangerous interactions

between the drug and other remedies taken for that new illness.

 

Off-label drugs have been linked at times to deaths or severe side

effects, such as blindness and heart damage.

 

Children can respond to drugs very differently from adults, sometimes

with dangerous consequences. The FDA is now encouraging manufacturers

to test all drugs in children, though such studies are not required.

 

What is the law regarding the disclosure of off-label drug prescriptions?

 

No law in any state contains language specifically requiring doctors

to tell their patients when a prescribed treatment is off label. In

some states, including California, judges may allow injured patients

to use a doctor's lack of disclosure to bolster a malpractice suit.

Other state courts have ruled that the failure to disclose the

off-label status of a treatment is irrelevant in malpractice claims.

 

In California: what doctors must tell patients

 

Doctors in California must obtain informed consent to medical

treatment, though this does not necessarily mean written consent. The

physician is required to outline the benefits and any serious risks of

a drug or procedure.

 

Beyond that, doctors are responsible for disclosing other information

that they know, or should know, would be needed by a reasonable person

to make an informed decision to accept or reject the treatment.

 

California law does not explicitly require doctors to reveal that they

are prescribing a drug off label. But a jury in a malpractice case

might conclude, in some cases, that the patient needed that

information to make an informed choice. If a jury reached that

conclusion, the liability could be increased for a physician who

didn't disclose the drug's off-label status.

 

Chronicle research

Troubled treatments

 

Here is a sampling of some of the more high-profile off-label

controversies.

 

Drug (maker)

 

Paxil (GlaxoSmithKline)

 

FDA- approved use: Antidepressant for adults

 

Common off-label use: Antidepressant for children New York Attorney

General Eliot Spitzer sued the firm, saying it suppressed data

indicating that Paxil could increase the risk of suicide in children.

The company settled the lawsuit in 2004, agreeing to post negative

study results online, but admitted no wrongdoing.

Drug (maker)

 

Neurontin(Pfizer)

 

FDA- approved use: Treating epilepsy and pain related to shingles, a

skin disorder Common off-label use: Treating back pain, bipolar

disorder and many other illnesses Controversy: Drug was illegally

promoted for dozens of off-label uses; company pleaded guilty last

year to federal felonies related to marketing and agreed to pay the

government a $430 million fine.

Drug (maker)

 

Prempro/other hormone replacement therapy(Wyeth)

 

FDA- approved use: Treating symptoms of menopause and preventing

osteoporosis Common off-label use: Once prescribed widely in the

belief it would ward off heart disease, stroke, cancer and other

diseases of aging

 

Controversy: Large-scale clinical trials in recent years have found

that the hormone pills increased the risks of heart disease, stroke,

breast cancer and dementia. Use of the drugs, if necessary, is now

recommended for only the shortest possible amount of time.

Drug (maker)

 

Fen-phen: Pondimin and Redux (American Home Products/Wyeth), or

fenfluramine, used with phentermine -- a generic diet drug

 

FDA- approved use: Fenfluramine was approved as a short-termdiet drug

 

Common off-label use: The " fen-phen " combination of diet drugs was

used off label in long-term weight loss regimens

 

Controversy: Pondimin and Redux were withdrawn from the market in 1997

after the Mayo Clinic found heart valve damage among those taking

fen-phen.

Drug (maker)

 

Enkaid (Bristol Myers) and Tambocor (3M-Riker)

 

FDA- approved use: Treating life-threatening cases of irregular heartbeat

 

Common off-label use: Prescribed in the 1980s for people with

less-serious cases of " skipped heartbeat. "

 

Controversy: A large government study found in 1989 that the drugs

more than tripled the risk of death when given to patients with

less-serious cases of irregular heartbeat -- a use now discontinued.

 

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