Studies could alter treatment for depression, schizophrenia

[Guest guest]

I don't get how they can experiment on children. Comparing drugs cancels out

other known workable treatments like love and time that don't damage organs

or make people worse. Jim

http://www.post-gazette.com/pg/05208/544589.stm

Studies could alter treatment for depression, schizophrenia

Wednesday, July 27, 2005

By Leila Abboud, The Wall Street Journal

The results of the largest studies ever conducted of depression and

schizophrenia will be released in coming months, potentially transforming

the way patients are treated and shaking up some of the drug industry's most

lucrative markets.

The federally funded studies are part of a six-year push by the

mental-health division of the National Institutes of Health to come up with

reliable scientific data on the differences between drugs and treatment

strategies for the major psychiatric illnesses. The project comprises four

trials, in serious depression, bipolar disorder, schizophrenia and

adolescent depression.

The aim is to fill the information gap that plagues psychiatry, and hurts

the quality of care given to patients. Clinical trials that companies do to

get drugs approved aren't designed to provide the answers that doctors say

they really need. For one, these trials don't compare one drug with another,

because they are designed to show only whether a particular drug is

effective against an illness. Thus, psychiatrists have little guidance on

whether one drug works better than another or has fewer side effects than

another.

Also, at eight to 12 weeks long, drug-company trials are too short to reveal

how patients fare or what side effects crop up long-term. And, in order to

stay focused on a drug's efficacy on one illness, they exclude the sickest

patients and people with co-existing diseases.

The paucity of quality information about drugs has been a major issue in

recent years as concerns have emerged about side effects, and drug companies

have been criticized for hushing up unfavorable study results.

So, the NIH-funded trials aim to compare treatments to discover both

positive and negative impacts of the drugs, and to mimic the real world with

all of its imperfections. All kinds of patients are included and they are

followed for years. The trials -- which include thousands of participants,

versus the hundreds in a typical drug-company trial -- are conducted all

over the country and include community clinics and primary-care offices, not

just academic medical centers. As part of the $140 million effort, the NIH

is also collecting data on the cost effectiveness of the various treatments

and pitting older drugs, which are available as cheaper generics, against

newer blockbusters.

Grayson Norquist, a former NIH psychiatrist who played a big role in

conceiving the trials, says they aim to answer the main question doctors

face every day. " Of the several drugs I have to choose from, " says Dr.

Norquist, now at the University of Mississippi Medical Center, " which one

should I use for the person sitting in front of me? "

Enormous amounts of money are at stake if the trials reveal differences in

the safety and efficacy of various drugs. Antidepressants and antipsychotics

are the third- and fourth-biggest classes of drugs in the country after

cholesterol and heartburn medicines, with U.S. sales of $20.7 billion last

year. Much of that cost is borne by government health-care plans. Both

health-care payers and Wall Street investors are anxiously awaiting the

results of the two trials in coming months. (Results from the first arm of

the project, on adolescent depression, came out in August 2004 and showed

that a combination of antidepressants and therapy was the most effective

treatment. The study of bipolar disorder ends in September, and results will

be published after the analysis is completed.)

In addition to comparing drugs, the trials are trying to fill another gap in

the scientific literature: what to do with the many patients who don't get

better on their first drug. Psychiatrists do a lot of switching patients

from one antidepressant to another and tinkering with drug combinations.

None of this is backed up with good evidence, and it can take months to find

the right regimen. Practices and outcomes vary widely among doctors.

Steve saw a dozen doctors before finding the drugs that alleviated

his schizophrenia. The 45-year-old from Cedar Rapids, Iowa, first had

hallucinations as a freshman in college, and took haloperidol, an

older-generation antipsychotic, for years. He remained so anxious and

depressed he contemplated suicide. A newer antipsychotic, Clozaril, worked

better. But it was only when his doctor added Zyprexa to the mix that he

finally recovered.

" Clinicians are just basically practicing seat-of-their-pants pharmacology

based on their experience with patients, " said Lieberman, the

principal investigator on the schizophrenia study, which is known as CATIE.

" When they look for hard data in the scientific literature to base their

decisions on, they can't find it. "

The problem is especially acute in depression -- about half of patients

don't respond to standard antidepressant therapy. The depression study,

called STAR.D, tests whether the subsequent treatment strategies doctors

typically use for these patients actually work. It included 3,940 patients

across the country who were followed for five years.

All of the patients first take the antidepressant Celexa, from Forest

Laboratories Inc., which belongs to a class of drugs known as selective

serotonin reuptake inhibitors. Those who don't get better can choose whether

to try therapy or switch to other antidepressants -- either Pfizer Inc.'s

Zoloft, another SSRI, or GlaxoKline PLC's Wellbutrin or Wyeth's

Effexor, which work by different mechanisms in the brain. In the third and

fourth stages of the study, people who don't get better cycle through

various antidepressants and combinations of drugs.

The CATIE schizophrenia study pits eight antipsychotic drugs against each

other to determine their comparative effectiveness and safety. About 1,600

patients were enrolled and followed for 18 months.

In the first stage, patients are given either perphenazine (an older,

generic antipsychotic medication) or one of four newer drugs: Eli Lilly &

Co.'s Zyprexa, & 's Risperdal, AstraZeneca PLC's Seroquel or

Pfizer's Geodon. If they don't get better or encounter side effects, they

are switched to other antipsychotics, including the newest, Abilify from

Bristol-Myers Squibb Co.

One of the big benefits to patients of the CATIE trial will be high-quality,

rigorous information about the comparative side effects of psychiatry

medications. Concerns have emerged in recent years that some of the newer

medicines, known as atypical antipsychotics, can cause extreme weight gain,

worsen cholesterol and lead to diabetes. Although the Food and Drug

Administration required that all atypical antipsychotics carry a warning

about these side effects, the NIH trial might actually reveal whether

certain drugs in the class are worse than others.

The CATIE investigators are now analyzing the results and preparing them for

publication in September. But one striking fact has already emerged: nearly

70 percent of patients in the study didn't do well on their first drug, and

switched to another.

[Guest guest]

I don't get how they can experiment on children. Comparing drugs cancels out

other known workable treatments like love and time that don't damage organs

or make people worse. Jim

http://www.post-gazette.com/pg/05208/544589.stm

Studies could alter treatment for depression, schizophrenia

Wednesday, July 27, 2005

By Leila Abboud, The Wall Street Journal

The results of the largest studies ever conducted of depression and

schizophrenia will be released in coming months, potentially transforming

the way patients are treated and shaking up some of the drug industry's most

lucrative markets.

The federally funded studies are part of a six-year push by the

mental-health division of the National Institutes of Health to come up with

reliable scientific data on the differences between drugs and treatment

strategies for the major psychiatric illnesses. The project comprises four

trials, in serious depression, bipolar disorder, schizophrenia and

adolescent depression.

The aim is to fill the information gap that plagues psychiatry, and hurts

the quality of care given to patients. Clinical trials that companies do to

get drugs approved aren't designed to provide the answers that doctors say

they really need. For one, these trials don't compare one drug with another,

because they are designed to show only whether a particular drug is

effective against an illness. Thus, psychiatrists have little guidance on

whether one drug works better than another or has fewer side effects than

another.

Also, at eight to 12 weeks long, drug-company trials are too short to reveal

how patients fare or what side effects crop up long-term. And, in order to

stay focused on a drug's efficacy on one illness, they exclude the sickest

patients and people with co-existing diseases.

The paucity of quality information about drugs has been a major issue in

recent years as concerns have emerged about side effects, and drug companies

have been criticized for hushing up unfavorable study results.

So, the NIH-funded trials aim to compare treatments to discover both

positive and negative impacts of the drugs, and to mimic the real world with

all of its imperfections. All kinds of patients are included and they are

followed for years. The trials -- which include thousands of participants,

versus the hundreds in a typical drug-company trial -- are conducted all

over the country and include community clinics and primary-care offices, not

just academic medical centers. As part of the $140 million effort, the NIH

is also collecting data on the cost effectiveness of the various treatments

and pitting older drugs, which are available as cheaper generics, against

newer blockbusters.

Grayson Norquist, a former NIH psychiatrist who played a big role in

conceiving the trials, says they aim to answer the main question doctors

face every day. " Of the several drugs I have to choose from, " says Dr.

Norquist, now at the University of Mississippi Medical Center, " which one

should I use for the person sitting in front of me? "

Enormous amounts of money are at stake if the trials reveal differences in

the safety and efficacy of various drugs. Antidepressants and antipsychotics

are the third- and fourth-biggest classes of drugs in the country after

cholesterol and heartburn medicines, with U.S. sales of $20.7 billion last

year. Much of that cost is borne by government health-care plans. Both

health-care payers and Wall Street investors are anxiously awaiting the

results of the two trials in coming months. (Results from the first arm of

the project, on adolescent depression, came out in August 2004 and showed

that a combination of antidepressants and therapy was the most effective

treatment. The study of bipolar disorder ends in September, and results will

be published after the analysis is completed.)

In addition to comparing drugs, the trials are trying to fill another gap in

the scientific literature: what to do with the many patients who don't get

better on their first drug. Psychiatrists do a lot of switching patients

from one antidepressant to another and tinkering with drug combinations.

None of this is backed up with good evidence, and it can take months to find

the right regimen. Practices and outcomes vary widely among doctors.

Steve saw a dozen doctors before finding the drugs that alleviated

his schizophrenia. The 45-year-old from Cedar Rapids, Iowa, first had

hallucinations as a freshman in college, and took haloperidol, an

older-generation antipsychotic, for years. He remained so anxious and

depressed he contemplated suicide. A newer antipsychotic, Clozaril, worked

better. But it was only when his doctor added Zyprexa to the mix that he

finally recovered.

" Clinicians are just basically practicing seat-of-their-pants pharmacology

based on their experience with patients, " said Lieberman, the

principal investigator on the schizophrenia study, which is known as CATIE.

" When they look for hard data in the scientific literature to base their

decisions on, they can't find it. "

The problem is especially acute in depression -- about half of patients

don't respond to standard antidepressant therapy. The depression study,

called STAR.D, tests whether the subsequent treatment strategies doctors

typically use for these patients actually work. It included 3,940 patients

across the country who were followed for five years.

All of the patients first take the antidepressant Celexa, from Forest

Laboratories Inc., which belongs to a class of drugs known as selective

serotonin reuptake inhibitors. Those who don't get better can choose whether

to try therapy or switch to other antidepressants -- either Pfizer Inc.'s

Zoloft, another SSRI, or GlaxoKline PLC's Wellbutrin or Wyeth's

Effexor, which work by different mechanisms in the brain. In the third and

fourth stages of the study, people who don't get better cycle through

various antidepressants and combinations of drugs.

The CATIE schizophrenia study pits eight antipsychotic drugs against each

other to determine their comparative effectiveness and safety. About 1,600

patients were enrolled and followed for 18 months.

In the first stage, patients are given either perphenazine (an older,

generic antipsychotic medication) or one of four newer drugs: Eli Lilly &

Co.'s Zyprexa, & 's Risperdal, AstraZeneca PLC's Seroquel or

Pfizer's Geodon. If they don't get better or encounter side effects, they

are switched to other antipsychotics, including the newest, Abilify from

Bristol-Myers Squibb Co.

One of the big benefits to patients of the CATIE trial will be high-quality,

rigorous information about the comparative side effects of psychiatry

medications. Concerns have emerged in recent years that some of the newer

medicines, known as atypical antipsychotics, can cause extreme weight gain,

worsen cholesterol and lead to diabetes. Although the Food and Drug

Administration required that all atypical antipsychotics carry a warning

about these side effects, the NIH trial might actually reveal whether

certain drugs in the class are worse than others.

The CATIE investigators are now analyzing the results and preparing them for

publication in September. But one striking fact has already emerged: nearly

70 percent of patients in the study didn't do well on their first drug, and

switched to another.