AstraZeneca Settles Most Seroquel Suits By DUFF WILSON

July 28, 2011, 5:50 pm

The British drug maker AstraZeneca has settled in principle nearly all of the American product liability lawsuits over Seroquel, its blockbuster antipsychotic drug, the company said in a quarterly earnings report on Thursday.
All but 250 of the 28,700 cases have been settled, most with written agreements, AstraZeneca said in the securities filing. It had previously reported settling most of those cases, but the new filing showed how far the company has whittled away at the remaining product liability litigation. Last quarter, it had reported 2,600 outstanding cases.
Most of the plaintiffs argued that they had been misled about the risks of diabetes and weight gain caused by Seroquel, the company’s second-best-selling product with $5.3 billion in worldwide sales last year, behind the cholesterol drug Crestor.
In the filing on Thursday, AstraZeneca said it added $55 million last quarter to the previously reported $592 million set-aside, for a total of $647 million to settle the litigation.
“Is it a good move?” said Les Funtleyder, health care analyst for Miller Tabak. “Yes, anytime you can settle these suits, it’s good.”
The set-aside includes the $68.5 million that the drug maker agreed to pay in March to 37 states, settling charges that it had illegally marketed Seroquel.
AstraZeneca also had to pay $520 million last year to settle federal investigations into its marketing of Seroquel.
At that time, Kathleen Sebelius, the secretary of health and human services, had accused the company of paying kickbacks to doctors while promoting the drug for unapproved uses by children, the elderly, veterans and prisoners.
AstraZeneca did not admit to any misconduct, while settling the federal case and signing a corporate integrity agreement, essentially putting it on probation with the government.
The company also said in the filing that its legal fees in Seroquel cases amounted to $743 million, partly covered by insurance. That figure has risen from $688 million estimated a year ago.
If the estimates hold, AstraZeneca will have paid a total of about $1.9 billion to defend and settle the personal injury cases and government investigations.
The figure represents less than five months of Seroquel sales.
That is far less than Eli Lilly paid to settle similar charges regarding its antipsychotic drug Zyprexa. Lilly paid more than $1.2 billion to settle lawsuits in 2007 and $1.4 billion to the government in 2009, including a criminal fine of $515 million.
At the time, that fine was the largest ever for a United States corporation. It has since eclipsed by the $1.3 billion criminal fine Pfizer paid as part of a $2.3 billion settlement of charges it had illegally marketed the painkiller Bextra and other drugs.
Drug makers have become the biggest targets of government antifraud investigations.
Legal discovery in the Seroquel cases has provided some of the most embarrassing or damaging disclosures over AstraZeneca’s past research and marketing practices, including a 1997 memo praising the company’s work to put a “positive spin” on a “cursed study” and highlighting one official who “has done a great ‘smoke-and-mirrors’ job!”
Another internal e-mail unsealed in court said AstraZeneca had “buried” unfavorable studies. A publications manager for the company wrote, “the larger issue is how we face the outside world when they begin to criticize us for suppressing data.”
 

http://prescriptions.blogs.nytimes.com/2011/07/28/astrazeneca-settles-most-seroquel-suits/

Dan Markingson - Seroquel Suicide?

This is one of the first articles I read after my Seroquel Suicide Attempt. Tragic. This could have been me. My hearts aches for Dan and his mother.

 Charles Schulz under scrutiny for Seroquel study suicide

Is U of M department of psychiatry chair in the pocket of AstraZeneca?

A A A Comments (18) By Andy Mannix Wednesday, Feb 2 2011

Mary Weiss knew something wasn't right with her son.

courtesy of Mary Weiss

Seven years after her son Dan Markingson's suicide, Mary Weiss still blames the University of Minnesota's psychiatry department

courtesy of Mill City Video Services

Charles Schulz admitted during a 2007 deposition that he'd earned more than $150,000 from drug companies

Only a year before, Dan Markingson had seemed perfectly normal. But his latest letter from Los Angeles suggested a troubled mind.
He claimed he was about to become famous. He was at a crossroads in his life, and would soon have more free time. He even had a big movie premiere in the works.
"I knew then that something was wrong," says Weiss. "I knew that there wasn't a premiere, and when he said he was going to have a lot more free time, I thought he was quitting his job."
Weiss immediately jumped in her car and drove to California. When she arrived, she found her son far worse off than she'd feared. He was talking nonsense and couldn't be reasoned with.
Weiss tried to convince Markingson to come back to Minnesota, where she could look after him. But he had a stipulation: He would only return home if his dead grandmother Daisy told him to.
Weiss went to an internet cafe down the street and created an email account under the name "GuardianAngelDaisy." Pretending to be her own deceased mother, she urged Markingson to return to Minnesota. Eventually, he agreed.
He was home for only 10 days before he decided to return to California. Weiss pleaded with him to stay, but he refused. She could either drive him to the airport, or never see him again.
Weiss followed him to Los Angeles, where she again tried to urge her son to go back to Minnesota. But this time, his grandmother's emails weren't enough. Markingson wanted to talk to a higher authority: Michael the Archangel.
Weiss created another fake email account as Archangel Michael. The two exchanged emails for more than a week before Markingson finally agreed to fly home.
Once he was back, Weiss called the South St. Paul police. An officer came to her home to evaluate her son. During the interview, Markingson casually mentioned he would soon be attending a devil-worshipping event in Duluth, and might be ordered to kill people.
That triggered a trip to Fairview University Medical Center, where Markingson was diagnosed with psychosis and placed on a 72-hour hold.
In order to be released, Markingson agreed to a stay of commitment, which would allow him to leave the hospital as long as he followed a treatment plan. The plan involved Markingson enrolling in a study called Comparison of Atypicals in First Episode, or CAFE. The research was sponsored by AstraZeneca, maker of Seroquel, one of the anti-psychotic drugs being investigated.
When Weiss found out her son was a human guinea pig, she was furious. She called the hospital and tried to pull her son out of the treatment plan, to no avail. Although Markingson was mentally unfit, he was somehow able to consent to the drug trial.
Over the next few months, Markingson's condition only worsened, Weiss says. His doctor wouldn't return her calls, so she tried writing a letter to the head of the department, Dr. S. Charles Schulz. He didn't reply.
It wasn't until April 28, after Weiss's third letter, that she received a cursory response, in which Schulz wrote, "it was not clear to me how you thought the treatment team should deal with this issue."
Ten days later, on May 8, Markingson sat in the bathtub of the halfway house where he was staying and stabbed himself to death with a box cutter.
"I left this experience smiling!" read the suicide note.
   
MARKINGSON'S SUICIDE HAS cast a harsh spotlight on the University of Minnesota psychiatry department. The Federal Drug Administration, the Attorney General's Office, and the college's Internal Review Board all wanted to know how a 26-year-old research subject ended up dead.
So did his mom. After a year of combing through studies and public records, Weiss filed a malpractice suit against Schulz and the U of M, accusing them of putting Big Pharma's bottom line ahead of her son's mental health.
In December, a group of eight bioethicists at the U of M wrote a letter to the college's Board of Regents, demanding the appointment of an independent board to investigate whether lapses in ethics and judgment led to Markingson's suicide.
"This goes beyond everything and anything, and this should have brought the house down on the university," says Vera Sharav, president of the Alliance for Human Research Protection, a patient-advocacy group. "There has to be zero tolerance, because a lot hangs on it, including lives."
The issue will soon come to a head. The U of M has been investigating a complaint about Schulz's connections to Big Pharma and is expected to issue the results in a matter of weeks.
"If there's any question that the investigation was superficial, it ought to be by an independent group that can determine what the facts are," says Jerome P. Kassirer, former editor of the New England Journal of Medicine, who is familiar with the circumstances surrounding the Markingson case. "It looks worrisome to me."

http://www.citypages.com/2011-02-02/news/charles-schulz-under-scrutiny-for-seroquel-study-suicide/

Seroquel Suicide

I was not feeling well physically and emotionally. I felt out of balance. I would fluctuate between feeling helpless, sad, anxious and irritable, to feelings of optimism, coupled with racing thoughts and an inability to concentrate. I am a wife and mother of four wonderful children and I tried to suck it up...if Mama ain't happy, ain't nobody happy.

I improved my diet, exercised and took vitamins and supplements but nothing helped me to feel better.

I finally decided that I needed the help of a professional and made an appointment with a Psychiatrist. I explained my symptoms to him and was diagnosed as Bipolar Type 2.

The signs and symptoms of  Bipolar II disorder can be viewed at:
http://www.mayoclinic.com/health/bipolar-disorder/DS00356/DSECTION=symptoms

Well, this diagnosis really freaked me out. I was not "crazy!!!" But I knew that I did not want to continue to live with the sometimes debilitating symptoms I was experiencing so I decided to keep an open mind. The doctor decided to put me on 100 mg of Seroquel and would then increase the dose to 200 mg. Looking back I realize that at no time did he discuss the side effects of the drug which I feel was very negligent. When administering this potentially dangerous medication it was his responsibility to sit with me and discuss what I may expect and what to watch out for. This medical professional is treating patients who suffer from mental illness. There is a significant possibility that a patient like myself who is suffering from depression, anxiety, racing thoughts and an inability to concentrate may not read the leaflet attached to the medication or go online to do further research.  But I guess my 45 minutes was up and he had to get on to his next patient.

I read the leaflet attached to the med and went online to research it...scarey !!!!!!!

According to AstraZeneca (the makers of Seroquel) some of the side effects are as follows: Increased risk of suicidal thoughts or actions, high blood sugar and diabetes, increase in triglycerides and LDL, feeling dizzy or lightheaded upon standing, decreases in white blood cells (which can be fatal), tardive dyskinesia, weight gain, rapid heart beat, disturbance in speech or language, drowsiness.
http://www.seroquelxr.com/
Now you can understand why it was scarey to take this medication. So I made an informed decision to start taking Seroquel with an "it can't happen to me" mindset.

I took it before bedtime and it really knocked me out. In the morning I was extremely groggy and my speech was slurred. It was very upsetting for my family to see me this way. I explained that it was a side effect of Seroquel and would soon taper off which it did. 

I started feeling better...more balanced. Most of my symptoms subsided...yea !!!!! It felt good to feel good. Then my psychiatrist increased the dose to 200 mg. I asked him why he had to do this and was told that 200 mg was the optimum dose for me. Well OK

I started to feel very very sick. Rapid heartbeat (my pulse was 105 and is usually in the 70s), extreme agitation, nausea, confusion, twitching, fight or flight. I spoke with my doctor and told him how I was feeling and he told me that maybe I needed counseling. OMG he seriously said that. I wish that at that point I would have gone to the hospital and maybe someone would have recognized that my symptoms were directly related to Seroquel use. My family and I could have been spared the trauma and tragedy that was about to be slammed upon us.

One Saturday three weeks ago my husband and I were saying that this is one of the most exciting times of our lives. Among the many things to rejoice we were starting a business with great potential for success. At 5pm we met with a web developer to get a website built. I had to leave the meeting early to take our daughter to a party. Then fast forward to me that evening in my bathroom swallowing massive amounts of pills. Looking back I felt like I was in a trance, but that's not quite right, I really didn't feel anything, I was just doing it!! The next thing I remember was looking over and seeing a dark shadow sitting in the corner which turned out to be my husband. I heard him say to me, "Do you know where you are? You are at the hospital in ICU." 

My husband found me lying on my back on the bathroom floor. I was blue, had thrown up and was literally drowning in my own vomit. I was barely breathing. He told the kids to call 911 and started doing CPR. Then the house was filled with paramedics, fire fighters and police. Terrible, terrible that my family had to witness this. My son said he saw my arm and it was blue. He later told me that it looked like a dead arm but that it couldn't be because it was his mom's arm.

I was taken to the hospital to ICU with a slim chance of survival. My husband was told that if I did survive there was a good possibility that I would suffer from brain and/or heart damage. Needless to say the waiting was agonizing for my loved ones. Two days later I regained consciousness and my first foggy thought was, "How did I get here?" The tests performed proved that I did not have any of the physical damage suspected but the emotional damage is beyond words.

I was then put on a 72 hour hold and transferred to a psych hospital.  I felt like I was living someone else's life. How did this happen? Why did this happen? There was no reason, no motivation, no catalyst. This was not me. I did not do this. Yet here I was in a mental hospital, super groggy and foggy, terrible pain, angry, confused, disgusted, ashamed. 

Going home was bittersweet. Ecstatic to be back with my sweet family but extremely painful to face them with what I had done. My young daughter asked me, "Why were you so unhappy Mommy? Why did you want to leave me?" I wasn't and I didn't. We are moving on with the strength of our love for one another but I can't help to have a heart wrenching pain that this will be remembered as the summer that Mom tried to commit suicide.

Express Scripts will buy rival Medco for $29.1B

NEW YORK (AP) — Express Scripts and Medco Health Solutions, the largest U.S. pharmacy benefits management companies, said Thursday they will combine in a deal worth $29.1 billion in cash and stock.

The companies manage prescription drug benefits and look for ways to cut costs for health plan sponsors and members. Combined, they handled more than 1.7 billion prescriptions in 2010 and reported almost $110 billion in revenue. The new Express Scripts Holding Inc. could use its size to negotiate bigger discounts on drug prices, although it would also have less competition than Medco and Express Scripts individually.

Express Scripts of St. Louis, will buy its rival for $71.36 per share. Medco's shareholders will get $28.80 per share in cash and 0.81 shares of Express Scripts for each share they own. That's a premium of 27.9 percent based on Medco's closing price of $55.78 Wednesday. Shares of the Franklin Lakes, New Jersey, company have traded between $43.45 and $65.39 in the last year.

Medco shares rose $10.20, or 18 percent, to $65.98 in early trading, while Express Scripts shares gained $3.81, or 7.3 percent, to $56.35.

The surprise announcement follows a string of contract losses for Medco, the largest PBM in terms of revenue. On Thursday the company said it has booked about $800 million in new business for 2012, which is far less than the business it has lost. It also announced that UnitedHealthcare decided not to renew a contract that ends on Dec. 31, 2012.

So far this year, Medco has said the Federal Employees Health Benefit Program, the California Public Employees' Retirement System, and a Universal American unit would take their business elsewhere after their current contracts expire. The federal employee benefits contract alone brought Medco about $3 billion in annual revenue.

The deal is expected to close in the first half of 2012, pending approval from regulators and from shareholders of both companies. Express Scripts shareholders will own 59 percent of the new company, which will be based in St. Louis. Express Scripts Chairman and CEO George Paz will lead the larger Express Scripts, and the board of directors will expand to include two independent Medco directors.

Including the Medco acquisition, Paz said Express Scripts has made seven major deals since 1997, when his tenure began. He said three of those deals doubled the size of the company.

The companies said they have identified $1 billion in potential cost savings from the combination, which amounts to 1 percent of the combined company's costs. They said the deal will boost their profits slightly in the first full year after closing if integration costs and other expenses are excluded. The benefit is expected to increase in future years.

Express Scripts' largest competitor after the deal would be drugstore and PBM CVS Caremark Corp., which handled about 585 million claims in 2010.

Both Express Scripts and Medco also reported quarterly results.

 

http://news.yahoo.com/express-scripts-buy-rival-medco-29-1b-104051951.html

AstraZeneca continues to mass market Seroquel despite safety concerns & sordid history

http://seroquellawsuitblog.blogspot.com/2011/07/astrazeneca-continues-to-mass-market.html

Sunday, July 3, 2011

AstraZeneca continues to mass market Seroquel despite safety concerns & sordid history - it's still raining profits from this storm cloud of deceit

People Magazine June 20, 2011

AstraZeneca continues to mass market Seroquel despite safety concerns & sordid history - it's still raining profits from this storm cloud of deceit

Get Off of My Cloud

  

From: Counterpunch.org/MarthaRosenberg

Seroquel's Toll

By MARTHA ROSENBERG  
January 24, 2011

Even though AstraZeneca's antipsychotic Seroquel is the fifth best-selling medication in the US according to drugs.com, exceeded only by Lipitor, Nexium, Plavix and Advair diskus, its safety, effectiveness, clinical trial and promotion records are highly checkered.

An original backer, psychiatrist Richard Borison, was sentenced to a 15-year prison sentence in 1998 for a pay-to-play Seroquel research scheme.

Its US medical director Wayne MacFadden had sexual affairs with two different women involved with Seroquel research, say published reports.

Chicago psychiatrist Michael Reinstein received $500,000 from AstraZenenca and wrote 41,000 prescriptions for Seroquel reports the Chicago Tribune and ProPublica.

Psychiatrist Charles Nemeroff who left Emory University in disgrace after a Congressional investigation for unreported pharma income, promoted Seroquel in continuing medical education courses according to the web site of psychiatrist Daniel Carlat.

Florida child psychiatrist Jorge Armenteros was chairman of the FDA committee responsible for recommending Seroquel approvals while a paid AstraZeneca speaker himself, said the Philadelphia Inquirer in 2009.

Psychiatrist Charles Schulz' high profile pro-Seroquel presentations are suspected of being colored by his AstraZeneca income says the Minneapolis Star Tribune.

And unexplained Iraq and Afghanistan troop deaths are linked to Seroquel reported the Associated Press in August.

Originally approved for schizophrenia in 1997, Seroquel has subsequently been approved for bipolar disorder, for some groups of kids and as an add-drug for depression. This "indications creep" has mostly flown below the public's radar. Seroquel expansion to treat children in late 2009, for example, was noted as a mere "label change" on the FDA web site. Hello?

Even without its depression indication, Seroquel is big business for AstraZeneca, earning $4.9 billion in sales in 2009. It is the drug that North Carolina's Medicaid spends the most on: $29.4 million per year, reports the Charlotte News and Observer.

But now, as AstraZeneca rolls out its "Still Trying to Get Ahead of Your Depression" campaign, there are new questions about Seroquel's safety and effectiveness.

According to an FDA warning letter, an AstraZeneca sales representative during an unsolicited sales call on January 3, 2008 sold Seroquel as a treatment for major depressive disorder to a physician before it was approved for MDD, an infraction which is illegal.

Once Seroquel was approved for depression (as an add-on treatment to an antidepressant for patients with major depressive disorder who not have an adequate response to antidepressant therapy), its leave-behind sheets drew another FDA warning letter.

AstraZeneca implied patients would achieve "remission" from depression with Seroquel XR (extended release) as opposed to with an antidepressant alone, says FDA -- a claim not backed up by clinical experience.

Seroquel's effect on depression has only been demonstrated in two, six-week trials FDA further said and six weeks is "not a long enough time period to adequately assess remission." (It was approved...why?)

Also the case study of "Catherine F." depicted in leave-behind sheets is inaccurate says FDA because it suggests Seroquel alleviates "symptoms of sadness and loss of interest when this has not been demonstrated by substantial evidence or substantial clinical experience." (It was approved...why?)

Even AstraZeneca's own briefing to the FDA committee in 2009 admits a "failed study" in which both Seroquel and Lexapro "failed to differentiate from placebo" which is Clinical Trial for "didn't work."

Nor did AstraZeneca adequately disclose Seroquel risks says FDA which include increased mortality in elderly patients with dementia-related psychosis, suicidality, neuroleptic malignant syndrome, hyperglycemia and diabetes mellitus, hyperlipidemia, weight gain and other serious side effects.

In fact, in addition to risks like cataracts, seizures and increases in blood pressure in children and adolescents, already on the Seroquel label, FDA asked AstraZeneca to add the "risk of EPS and withdrawal syndrome in neonates" a few months ago: movement disorders which can affect mothers' babies if the mothers are taking Seroquel and stop.

But the FDA might also look at what the government's other hand is doing. In May the Office of the Army Surgeon General's final report on the findings of its Pain Management Task Force unabashedly hawks Seroquel for an unapproved use.

"Physicians should consider these medications for sleep disorders," says the 163-page report," listing Ambien and Seroquel (quetiapine) "for nightmares" even though Seroquel has never been approved for insomnia, sleep disorders or "nightmares."

Maybe the government will send itself a warning letter. 

Seroquel Use = Diabetes = More Drugs = $$$$ For Big Pharm

Recently conducted studies have found a link between Seroquel and a higher risk of developing blood sugar disorders, including hyperglycemia, diabetic ketoacidosis, and diabetes.
After diagnosis with diabetes, your doctor may prescribe a specific drug regimen. Every person is different, so your Diabetes treatment will be tailored to your needs. We’ve listed common drugs that may be prescribed for diabetes.

• Actos Oral
• Amaryl Oral
• Apidra SoloStar SubQ
• AVANDAMET Oral
• Avandaryl Oral
• Avandia Oral
• Byetta SubQ
• Cozaar Oral
• Diabeta Oral
• Glucophage Oral
• Glucotrol Oral
• Glucovance Oral
• Glynase Oral
• Humulin R U-500 "Concentrated" Inj
• Lantus SubQ
• Metaglip Oral
• Onglyza Oral
• Prandimet Oral
• Prandin Oral
• Precose Oral
• RIOMET Oral
• Starlix Oral
• SymlinPen 120 SubQ
• SymlinPen 60 SubQ
• Xenical Oral

Seroquel and Diabetes

Recently conducted studies have found a link between Seroquel and a higher risk of developing blood sugar disorders, including hyperglycemia, diabetic ketoacidosis, and diabetes. Diabetes is a metabolic condition in which the body cannot breakdown glucose properly. Experts estimate that at least 171 million individuals worldwide suffer from diabetes and the number is expected to double by 2030. In 2005, diabetes sufferers in the United States totaled 20.8 million people, and it is believed that there are over 6 million people with diabetes that have gone undiagnosed and another 41 million people who could be considered pre-diabetic.

The association between the usage of Seroquel and an increased risk of developing a blood sugar disorder led the FDA to request that the warning label on Seroquel be changed to include the new information. Seroquel is one of the 6 anti-psychotic medications believed to promote diabetes, high cholesterol, and obesity. The clinical trials conducted found that the patients taking Seroquel developed diabetes over three times more often than the patients who were taking anti-psychotic medications that had been on the market for a longer period of time. Doctors received information warning them to carefully monitor any of their patients who were taking Seroquel to determine whether they were developing diabetes. The risk was not determined to be great enough to warrant a recall of Seroquel, but healthcare professionals are advised to weight the risks and benefits carefully before deciding to prescribe Seroquel to any individual.
http://www.schmidtandclark.com/seroquel-diabetes

Family Involvement in Suicide Prevention

May 2nd, 2011 by Aparajita

 

 

 

 

 

 

Suicide is becoming a glaring as well as sad cause for premature deaths. The family must understand it's responsibility and power in preventing suicides.

Every individual looks forward to a happy and fulfilling life with his family; but there are certain unfortunate individuals and families who go through the agonies of suicidal tendencies. The individual who attempts suicide may have a tendency or may be suffering from a trauma, depression or stress. The family members suffer no less as they remain in constant anxiety regarding the suicidal individual and needs to keep total vigilance on him. This is not an easy task and neither is the situation normal. The person going through the suicidal tendency may be in a very pathetic condition; for him suicide is the last option when he may feel that all doors to his happiness has closed and being alive is only creating more pain for him and his loved ones. He thinks in a very negative way and feels that the only solution lies in ending him.

Many times the family may not be understanding or recognizing the warning signs; to them the withdrawal and depressive signs and symptoms of the suicidal person may seem just a phase which will get over. Many families have repented later feeling that if only they could have understood the signs and prevented losing their loved one through suicide. Family members or close friends must never hesitate to feel free and talk with the concerned person whom they suspect to be contemplating suicide. Their assuring words, love and support may make the person change his mind about suicide. If the family is unable to help they should immediately seek professional help to save the life from suicide.
Facts about suicide
To identify the warning signs and symptoms of suicide we must first know certain important facts about suicide. It is commonly thought that those who are contemplating suicide don’t actually talk about it. This is a very wrong judgment. Often those who have spoken about ending themselves or kept referring to their death and had not been taken seriously had actually ended up committing suicide. Therefore verbal references to suicide should be taken seriously.
A person not necessarily has to be suffering from a mental disorder to commit suicide. Many people who are not diagnosed of any mental illness may not be psychologically well equipped or strong to handle a mishap or a misfortune. They may remain depressed and extremely sad until they take such a drastic step as suicide.
Another wrong belief about suicidal person is that nothing can prevent them from committing suicide. Well it should be mentioned here that the persons who commit suicide are in many cases do it in an impulse without actually intending to do so. Suicidal people actually don’t want to commit suicide; its just that they have lost their self esteem drastically which needs to be reassured. It’s also not true they don’t ask for help; in many cases they had taken help before committing suicide. Nobody can create fear by speaking gloomy things about suicide; rather it’s wise and logical to face the issue and speak to the person in a loving and friendly way while trying to make him realize the futility of suicide and utility of life.
Identifying possible suicide victims
People who have a mental disorder like psychotic or mood disorders like depression or bipolar disorder are more prone to suicidal attempts. People who carry a family history or are victims of substance abuse may also contemplate suicide sometime or the other. Many times an otherwise normally functioning person may also fall into a vicious and dangerous circle of hopelessness and despair that he may contemplate suicide. Identifying and understanding such victims are more difficult as they don’t have the predisposing conditions for suicidal tendencies. Family members have to be more careful with teenagers as they are passing through an emotionally vulnerable age when they can act in an impulse if they are hurt and may harm themselves fatally. Suicides are often committed in an impulse; a failure in exam, a breakup or heart break or a public humiliation all may mount up to an unpredictable suicide. 
Identifying possible signs and symptoms of an impending suicide
The most important signs of an impending suicide are repeated references to death either verbally or even non-verbally like writing about death. Hopelessness and depression should also be taken seriously. Sometimes the suicidal individual may be collecting sleeping pills or deadly objects. A prevailing sense of self loathing, loss of self esteem, hopelessness and doom keeps the person occupied. There may be a sudden change in behavior like preparing a will, distributing loved objects and saying things like “all will be fine now” or “there won’t be any more grief” or “goodbye” and also making proper provisions and arrangements for loved ones.  Their death wish may become apparent in their reckless behaviors and becoming aloof from everybody.
Family involvement in suicide prevention
A family should remember that what family members can do together may even be more powerful and effective than what experts can do. The love, support and assurance from family members can create wonders and change the life pattern of the self doomed suicidal person. The best way is to talk and find out what the person has to say, assist him in speaking up rather than letting him be by himself.
Simply listening and letting the person give vent to his negative feelings can make a big difference. It’s better to be approached by the family member to whom the person is most close with; may be a parent, a grand parent or a sibling or may be even a relative. Avoid any sort of argument; rather provide support and hope. Give examples or make up examples where people have come out from similar distressing situations and are now doing very well in life.
Parents of teenagers must avoid putting excess stress on them for better performance; they must not over protect or show indifference to their kids. Keep a balance between protection and a level of trust. Rather than blaming the kid for a wrong doing be supportive if the kid is depressed and grieving for a mishap like failure.

Read more: http://www.bukisa.com/articles/492254_family-involvement-in-suicide-prevention#ixzz1SgQA5dzT

http://www.bukisa.com/articles/492254_family-involvement-in-suicide-prevention

What Can I Do to Help Someone Who May Be Suicidal?

http://www.metanoia.org/suicide/whattodo.htm

Suicde Facts

http://www.usuhs.mil/psy/pdf/militaryfamilyshouldknow.pdf

Suicide Action Steps and Resources

Action Steps
 
If you are experiencing any of these signs/symptoms, please seek help. If someone you know is experiencing these symptoms, please offer help. If you think someone is suicidal, do not leave him or her alone. Try to get the person to seek immediate help from his/her doctor, bring them to the nearest hospital emergency room, or call 911. If possible, try to eliminate access to firearms or other potential means for self-harm.

Resources
 
National Suicide Prevention Lifeline: ■■1-800-273-TALK (1-800-273-8255)
 
Suicide Prevention Resource Center: ■■www.sprc.org
 
American Association of Suicidology: ■■http://www.suicidology.org/web/guest/thinking-about-suicide
 
Military Onesource: ■■1-800-342-9647, www.militaryonesource.com

Seroquel® Suicide

As with any antipsychotic medication, there are Seroquel® suicide risks associated with the use of this prescription medication. Seroquel® use has not been formally associated with significant suicide risks, but Seroquel® suicide is a side effect that is important to consider. Seroquel® was originally approved by the FDA in 1997 to treat the hallucinations, delusions, and paranoia of schizophrenia. In 2004, the FDA approved AstraZeneca's Seroquel® to treat bipolar patients. Seroquel® is prescribed for a number of off-label uses including anxiety, depression, Alzheimer's, and dementia as well.
Seroquel® suicide risks are a factor to consider regardless of a person's illness, though Seroquel® suicide risks may be particularly notable in patients who take this medication for bipolar disorder. Bipolar disorder affects three to four percent of the population and is considered the sixth leading cause of disability. Bipolar disorder is characterized by vacillations between extreme highs and lows in mood and mental state from mania to depression.
Patients who suffer from Bipolar disorder often experience extreme states of mania characterized by euphoria, hyperactivity, impulsivity, racing thoughts, and the like. These patients also typically experience extreme lows characterized by depression, sadness, and potentially, suicidal ideations. Seroquel® suicide information indicates that one out of four bipolar patients will attempt suicide at some point in their lives. It is estimated that more than ten percent of bipolar patients will commit suicide. These risks, in and of themselves, raise the issue of Seroquel® suicide risks, since this patient population is at an increased risk of suicide due to their condition.
Seroquel® was approved to treat bipolar disorder in large part because of clinical trial evidence suggesting its efficiency in reducing Seroquel® suicide and other risks. The BOLDER trial included over one thousand bi-polar participants who were given Seroquel® or a placebo. The results suggest that Seroquel® use caused a decrease in subject's core depressive symptoms and successfully alleviated manic symptoms soon after treatment commenced. This trial also suggested a very low rate of unfavorable treatment-emergent symptoms of mania.
The results of this clinical trial suggest that Seroquel® suicide risks may actually be reduced in certain patient populations. There are case studies which point to the contrary, suggesting that Seroquel® suicide and other risk factors may be increased by this drug's use. Some patients who have taken Seroquel® for schizophrenia have exhibited treatment induced states of mania that did not occur prior to Seroquel® use and remitted after terminating treatment. In such cases, Seroquel® suicide risks may be greater.
The majority of evidence to date suggests that Seroquel® use prevents suicide more often than it causes suicidal behaviors in patients. Because the risk of Seroquel® suicide does exist, it is important that patients be carefully monitored for any signs of Seroquel® side effects or other changes in behavior. To learn more about Seroquel® suicide, you may wish to speak with an attorney who can advise you of your legal rights and options.

http://www.adrugrecall.com/seroquel/suicide.html

Side Effects May Include Lawsuits

The New York Times
By Duff Wilson
October 2, 2010

FOR decades, antipsychotic drugs were a niche product. Today, they’re the top-selling class of pharmaceuticals in America, generating annual revenue of about $14.6 billion and surpassing sales of even blockbusters like heart-protective statins.

Department of Justice Statements on the Five Major Companies Selling Anti-Psychotic Drugs: AstraZeneca Bristol-Myers Squibb Eli Lilly Johnson and Johnson Pfizer

While the effectiveness of antipsychotic drugs in some patients remains a matter of great debate, how these drugs became so ubiquitous and profitable is not. Big Pharma got behind them in the 1990s, when they were still seen as treatments for the most serious mental illnesses, like hallucinatory schizophrenia, and recast them for much broader uses, according to previously confidential industry documents that have been produced in a variety of court cases.
Anointed with names like Abilify and Geodon, the drugs were given to a broad swath of patients, from preschoolers to octogenarians. Today, more than a half-million youths take antipsychotic drugs, and fully one-quarter of nursing-home residents have used them. Yet recent government warnings say the drugs may be fatal to some older patients and have unknown effects on children.
The new generation of antipsychotics has also become the single biggest target of the False Claims Act, a federal law once largely aimed at fraud among military contractors. Every major company selling the drugs — Bristol-Myers Squibb, Eli Lilly, Pfizer, AstraZeneca and Johnson & Johnson — has either settled recent government cases for hundreds of millions of dollars or is currently under investigation for possible health care fraud.
Two of the settlements, involving charges of illegal marketing, set records last year for the largest criminal fines ever imposed on corporations. One involved Eli Lilly’s antipsychotic, Zyprexa; the other involved a guilty plea for Pfizer’s marketing of a pain pill, Bextra. In the Bextra case, the government also charged Pfizer with illegally marketing another antipsychotic, Geodon; Pfizer settled that part of the claim for $301 million, without admitting any wrongdoing.

A Glimpse of Industry Marketing

The companies all say their antipsychotics are safe and effective in treating the conditions for which the Food and Drug Administration has approved them — mostly, schizophrenia and bipolar mania — and say they adhere to tight ethical guidelines in sales practices. The drug makers also say that there is a large population of patients who still haven’t taken the drugs but could benefit from them.
AstraZeneca, which markets Seroquel, the top-selling antipsychotic since 2005, says it developed such drugs because they have fewer side effects than older versions.
“It’s a drug that’s been studied in multiple clinical trials in various indications,” says Dr. Howard Hutchinson, AstraZeneca’s chief medical officer. “Getting these patients to be functioning members of society has a tremendous benefit in terms of their overall well-being and how they look at themselves, and to get that benefit, the patients are willing to accept some level of side effects.”
The industry continues to market antipsychotics aggressively, leading analysts to question how drugs approved by the Food and Drug Administration for about 1 percent of the population have become the pharmaceutical industry’s biggest sellers — despite recent crackdowns.
Some say the answer to that question isn’t complicated.
“It’s the money,” says Dr. Jerome L. Avorn, a Harvard medical professor and researcher. “When you’re selling $1 billion a year or more of a drug, it’s very tempting for a company to just ignore the traffic ticket and keep speeding.”
NEUROLEPTIC drugs — now known as antipsychotics — were first developed in the 1950s for use in anesthesia and then as powerful sedatives for patients with schizophrenia and other severe psychotic disorders, who previously might have received surgical lobotomies.
But patients often stopped taking those drugs, like Thorazine and Haldol, because they could cause a range of involuntary body movements, tics and restlessness.
A second generation of drugs, called atypical antipsychotics, was introduced in the ’90s and sold to doctors more broadly, on the basis that they were safer than the old ones — an assertion that regulators and researchers are continuing to review because the newer drugs appear to cause a range of other side effects, even if they cause fewer tics.
Contentions that the new drugs are superior have been “greatly exaggerated,” says Dr. Jeffrey A. Lieberman, chairman of the psychiatry department at Columbia University. Such assertions, he says, “may have been encouraged by an overly expectant community of clinicians and patients eager to believe in the power of new medications.”
“At the same time,” he adds, “the aggressive marketing of these drugs may have contributed to this enhanced perception of their effectiveness in the absence of empirical evidence.”
Others agree. “They sold the story they’re more safe, when they aren’t,” says Robert Whitaker, a journalist who has written two books about psychiatric medicines. “They had to cover up the problems. Right from the start, we got this false story.”
The drug companies say all the possible side effects are fully disclosed to the F.D.A., doctors and patients. Side effects like drowsiness, nausea, weight gain, involuntary body movements and links to diabetes are listed on the label. The companies say they have a generally safe record in treating a difficult disease and are fighting lawsuits in which some patients claim harm.
The cases, both civil and criminal, against many of the world’s largest drug makers have unveiled hundreds of previously confidential documents showing that some company officials were aware they were using questionable tactics when they marketed these powerful, expensive drugs.
Such marketing, according to analysts and court documents, included payments, gifts, meals and trips for doctors, biased studies, ghostwritten medical journal articles, promotional conference appearances, and payments for postgraduate medical education that encourages a pro-drug outlook among doctors. All of these are tools that federal investigators say companies have used to exaggerate benefits, play down risks and promote off-label uses, meaning those the F.D.A. hasn’t approved.
Lawyers suing AstraZeneca say documents they have unearthed show that the company tried to hide the risks of diabetes and weight gain associated with the new drugs. Positive studies were hyped, the documents show; negative ones were filed away.
According to company e-mails unsealed in civil lawsuits, AstraZeneca “buried” — a manager’s term — a 1997 study showing that users of Seroquel, then a new antipsychotic, gained 11 pounds a year, while the company publicized a study that asserted they lost weight. Company e-mail messages also refer to doing a “great smoke-and-mirrors job” on an unfavorable study.
“The larger issue is how do we face the outside world when they begin to criticize us for suppressing data,” John Tumas, then AstraZeneca’s publications manager, wrote in a 1999 e-mail. “We must find a way to diminish the negative findings,” he added. “But, in my opinion, we cannot hide them.”
Tony Jewell, an AstraZeneca spokesman, said last week that the company had turned over all that material to the F.D.A. as part of the approval process and updated its label over the years to show the latest safety information.
Dr. Stefan P. Kruszewski, a Harvard-educated psychiatrist who once worked as a paid speaker for several drug makers, became a government informant and now consults for plaintiffs suing drug companies. Earlier in his career, he spoke at events for Pfizer, GlaxoSmithKline and Johnson & Johnson as an advocate of antipsychotics. He said one company offered him incentives of $1,000 or more every time he talked to an individual doctor about one of its drugs.
“When I started speaking for companies in the late 1980s and early ’90s, I was allowed to say what I thought I should say consistent with the science,” he recalls. “Then it got to the point where I was no longer allowed to do that. I was given slides and told, ‘We’ll give you a thousand dollars if you say this for a half-hour.’ And I said: ‘I can’t say that. It isn’t true.’ ”
Slides for one new antipsychotic drug contended that it had no neurological side effects. “They made it all up,” Dr. Kruszewski said. “It was never true.”
Read entire article:  http://www.nytimes.com/2010/10/03/business/03psych.html?_r=2
http://www.cchrint.org/2010/10/04/antipschotic-drugs%E2%80%94side-effects-may-include-lawsuits/ 

AstraZeneca paying $68.5M in Seroquel settlement

By MATTHEW PERRONE

The Associated Press
Thursday, March 10, 2011; 2:25 PM

WASHINGTON -- AstraZeneca will pay $68.5 million as part of a multistate settlement over allegations that the drug developer promoted its blockbuster psychiatric drug Seroquel for insomnia, Alzheimer's and other unapproved uses.

The New Jersey Attorney General's Office announced the agreement Thursday, describing it as the largest multistate pharmaceutical settlement of its kind. New Jersey will receive $1.85 million from the deal with 36 other states and the District of Columbia as party to the settlement.
The states alleged that salespeople for AstraZeneca promoted its anti-psychotic Seroquel for off-label, or unapproved uses, and did not disclose side effects of the pill, which include weight gain and muscle spasms.
"Consumers rightfully expect pharmaceutical companies to engage in responsible marketing efforts that are consistent with approved purposes," said Thomas Calcagni, acting director of New Jersey's division of consumer affairs.

Seroquel is approved to treat schizophrenia, bipolar disorder and depression, though the majority prescriptions are for off-label uses like insomnia. The drug, approved in 1997, is AstraZeneca's second-best-selling product, with U.S. sales of $5.3 billion last year. But that success has been marred by frequent allegations that the company illegally marketed the drug and downplayed its risks.
Seroquel's side effects, including blood sugar increases, weight gain and uncontrollable muscle spasms, have resulted in thousands of lawsuits from patients. The drugmaker had settled nearly 25,000 personal injury lawsuits related to Seroquel at the end of 2010, with 3,950 remaining.
Pharmaceutical companies are prohibited from marketing drugs for unapproved uses, though doctors are free to prescribe them as they choose.
London-based AstraZeneca denied any wrongdoing.
"While we deny the allegations, AstraZeneca believes it is important to bring these matters to a close and move forward with our business of providing medicines to patients," said company spokesman Tony Jewell, in a statement.
Thursday's deal is the second multimillion-dollar Seroquel settlement brought by government prosecutors in the past two years. Last April AstraZeneca agreed to pay $520 million to settle similar allegations brought by the federal Department of Justice.
The new settlement stemmed from a separate three-year investigation led by the Attorney General of New Jersey. As part of the agreement AstraZeneca must publish any gifts or payments to physicians on a public website. The company also agreed to make sure that payment incentives to sales representatives do not encourage off-label promotion.
Allegations of off-label drug marketing have become increasingly common in the past decade, with the drug industry eclipsing all others as the source of fraud-related settlements with the federal government. Approximately 80 percent of the $3.1 billion in penalties collected last fiscal year by the government came from the health care sector, including drugmakers, insurers and hospitals, according to Taxpayers Against Fraud.
----
AP Business Writer Damian Troise in New York contributed to this report.
http://www.washingtonpost.com/wp-dyn/content/article/2011/03/10/AR2011031003328.html

Top Warning Signs of Diabetes From Debra Manzella, R.N.

Look For These Signs and Symptoms of Diabetes:

Many of the signs of Type 1 and Type 2 diabetes are similar. In both, there is too much glucose in the blood and not enough in the cells of your body. High glucose levels in Type I are due to a lack of insulin because the insulin producing cells have been destroyed. Type 2 diabetes occurs when the body's cells become resistant to insulin that is being produced. Either way, your cells aren't getting the glucose that they need, and your body lets you know by giving you these signs and symptoms.

• What is Type 1 Diabetes?
• What is Type 2 Diabetes?
• Risk Factors for Gestational Diabetes

Frequent trips to the bathroom:

Are you visiting the bathroom much more lately? Does it seem like you urinate all day long? Urination becomes more frequent when there is too much glucose in the blood. If insulin is nonexistent or ineffective, the kidneys can't filter glucose back to the blood. They become overwhelmed and try to draw extra water out of the blood to dilute the glucose. This keeps your bladder full and it keeps you running to the bathroom.

Unquenchable Thirst:

If it feels like you can't get enough water and you're drinking much more than usual, it could be a sign of diabetes, especially if it seems to go hand in hand with frequent urination. If your body is pulling extra water out of your blood and you're running to the bathroom more, you will become dehydrated and feel the need to drink more to replace the water that you are losing.

Losing Weight Without Trying:

This symptom is more noticeable with Type 1 diabetes. In Type 1, the pancreas stops making insulin, possibly due to a viral attack on pancreas cells or because an autoimmune response makes the body attack the insulin producing cells. The body desperately looks for an energy source because the cells aren't getting glucose. It starts to break down muscle tissue and fat for energy. Type 2 happens gradually with increasing insulin resistance so weight loss is not as noticeable.

Weakness and Fatigue:

It's that bad boy glucose again. Glucose from the food we eat travels into the bloodstream where insulin is supposed to help it transition into the cells of our body. The cells use it to produce the energy we need to live. When the insulin isn't there or if the cells don't react to it anymore, then the glucose stays outside the cells in the bloodstream. The cells become energy starved and you feel tired and run down.

Tingling or Numbness in Your Hands, Legs or Feet:

This symptom is called neuropathy. It occurs gradually over time as consistently high glucose in the blood damages the nervous system, particularly in the extremities. Type 2 diabetes is a gradual onset, and people are often not aware that they have it. Therefore, blood sugar might have been high for more than a few years before a diagnosis is made. Nerve damage can creep up without our knowledge. Neuropathy can very often improve when tighter blood glucose control is achieved.

Other Signs and Symptoms That Can Occur:

Blurred vision, skin that is dry or itchy, frequent infections or cuts and bruises that take a long time to heal are also signs that something is amiss. Again, when these signs are associated with diabetes, they are the result of high glucose levels in the body. If you notice any of the above signs, schedule an appointment with your doctor. He or she will be able to tell you if you have reason to be concerned about a diagnosis of diabetes.

http://diabetes.about.com/od/symptomsdiagnosis/p/Symptoms.htm

Seroquel & Weight Gain

http://www.livestrong.com/article/338815-seroquel-weight-gain/

Seroquel and Diabetes

http://bipolar-disorder.emedtv.com/seroquel/seroquel-and-diabetes.html

Journalist, member Of the Public, and Ex-Employee V AstraZeneca - Promoition of Seroquel

http://www.pmcpa.org.uk/files/2294%20&%202296%20&%202297%20August%202010_0.pdf

Seroquel XII: An Opinionated Postscript

Written By: 1 Boring Old Man

Posted on Monday 14 February 2011

Okay, you win. I’ll say it. No, there was no real reason to approve Seroquel. I didn’t say it because I don’t think I would’ve been able to turn it down myself in 1997. It wasn’t really a different time, but we didn’t know it then. There were Speaker’s Bureaus, and ghost-written articles [and textbooks], conflicts of interest galore, but such things were still under wraps and Psychiatry was in the middle of a tsunami of biology and false hopes – still in the after-glow of the SSRIs and hoping things from the newer drugs. And in 1997, we still believed what we were told. We thought that the Brave New World of Atypical Antipsychotics would liberate our patients from fear of Tardive Dyskinesia.

In 1997, I was practicing in Atlanta, teaching Psychoanalytic Candidates, and doing something like "outreach" – giving talks to Psychologists and Social Workers about Object Relations Theory and Traumatic Neurosis. We have a Psychoanalytic Studies program in the college were I also taught. heady graduate students, heads filled with Lacan. That is to say I no longer had any direct connection with the Psychiatry Department, even though I was on the clinical faculty. I thought the then Chairman, Dr. Charlie Nemeroff, was a self promoter and extremely naive in his blind adherence to some simplistic biological models of illness. By 1997, when he spoke at meetings, I would cut class because … well, I would just cut class. But I had no idea about how much he was in bed with the industry, or about his "poster-child" status , or that he was raking in personal money, or that many of his colleagues were too. I guess I thought he actually believed what sounded to me like drivel. I didn’t know the drivel was a cash cow.

By 1997, most of the public mental health facilities were running on bare bones, and an insurance policy with good coverage was about the only ticket into a hospital – so if you saw a psychotic patient, all you had was medication. The possibility of a medication that didn’t have all the extrapyramidal side effects and the specter of Tardive Dyskinesia would’ve looked mighty good. One line from Dr. Arvanitis’ papers worked, "Clinically significant weight gain, which was associated with SEROQUEL treatment, is often seen during treatment with antipsychotic agents." It was true. The other line, by the way, didn’t work, "In any case, weight gain over a 6-week period may or may not be clinically significant given that it may be a function of well-being resulting from improvement in psychosis." That was patent b-s at first glance. So I’m not sure that I would’ve realized what I now know – that Seroquel causes WEIGHT GAIN, not weight gain [and by the way again, there was no Trial 0015 to tell me that!].

The thing that haunts me about all of this is that as disgusted as I felt about the modern evidence-based medicine/DSM whichever turn in Psychiatry in 1997, I personally didn’t see all the corruption that now looks so obvious.  That’s one of the reasons I went back over the approval of Seroquel 14 years ago – to prove to myself how deceitful it really was. Back then, had I been on that F.D.A. panel, I may well have said, "No great shakes, but let’s give ‘em a shot. If it’s no good, doctors won’t prescribe it and the patients won’t take it." If you had said, "But this is going to be one of the most prescribed and revenue generating drugs in history!"  I wouldn’t have had any idea what you were talking about. And I feel guilty even saying that.

Actually, that thought I think I might’ve thought ["No great shakes, but let's give 'em a shot. If it's no good, doctors won't prescribe it and the patients won't take it"] turned out to be right. The patients in Trial 0015 did just that – relapsed or stopped taking it. I too believe that Seroquel has a lower incidence of neurological side effects than the other drugs, but I don’t use it for the Schizophrenic patients [Advil has a lower incidence of EPS too, but I don't use it in Schizophrenia either]. Seroquel doesn’t work well enough to get on my list. In cases where things aren’t desperate, I still try an Atypical first because of EPS/TD, but it often doesn’t get the job done. Seroquel isn’t the one I try. Risperdal is the only one I use because it’s the only one I’ve seen work with my own eyes.

It turns out that all approving Seroquel for Schizophrenia did was get it on the market and open up the doors for off-label use. Primary care Physicians don’t treat Schizophrenia, Psychotic [or profound] Depression, or even Mania. We do. And without outside influence, Seroquel would’ve died a quick death because it’s a weak sister, and because of the weight gain. Those billion dollar revenues come from office Psychiatrists who have drunk the Kool-ade and Primary Care Physicians. The F.D.A. thinks it has recurrently approved a drug to treat severe mental illnesses. What they’ve done is unleash a drug too soft to be usable for its intended patient population into circulation to fill the hole left by an increasing fear of the minor tranquillizers like Valium and its friends [I personally think that Seroquel is far more dangerous].

So, Seroquel was approved on a wish. What should have happened when it became clear that it had a big-time downside? Pull it from circulation. What about the indication creep? Psychiatrists have long used antipsychotics in manic patients or psychotically depressed patients during acute episodes. The F.D.A. didn’t need to be involved with that. We can figure that out all by ourselves. Those were marketing tricks that the F.D.A. should’ve declined. And Depression? Why would a lousy antipsychotic help depressed people? I don’t personally think it actually does any more than an anxiolytic or a sleeping pill might. Nobody’s thinking of submitting a sleeping pill for approval as an "add-on to antidepressants in MDD." That would be as absurd as the Seroquel indication is. I don’t fault the F.D.A. for approving the drug initially. I do question them for not pulling it when Trial 0015 came true. But I do damn the F.D.A. for approving the drug for other things that do nothing but validate off-label advertising and profiteering at the expense of our patients. They’re using F.D.A. approval as a gold-standard for their evidence-based medicine meme. Looking at those Clinical Trials we just reviewed, I didn’t see a whole lot of gold. In my opinion, that’s the place to start the reform movement. Every time I hear something like, "Now approved for augmentation of antidepressant monotherapy in treatment-resistant depression," I feel ashamed that I’m a Psychiatrist…

 

http://1boringoldman.com/index.php/2011/02/14/seroquel-xii-an-opinionated-postscript/

Seroquel XI: Through a Glass Darkly

Written By: 1 Boring Old Man
 
Posted on Monday 14 February 2011

 

The availability of the story of Seroquel‘s trip to market is fortuitous in that it came in the early days of the Internet and widespread use of email. The html driven WorldWideWeb was introduced in 1994, and by the period in question [1996-1997] was quite the rage in corporate life. I doubt Zeneca‘s staff realized how much of their communication would end up in the public domain [I'd bet that today's wheelings and dealings are done in evaporative media like phone calls or face-to-face]. There are several archives of  unsealed court documents that open the windows into the dark side of the Pharmaceutical industry and the Physicians who play on that playground – heavily populated with Psychiatrists:

• PsychRights: The Law Project for Psychiatric Rights
• Drug Industry Document Archives: University of California, San Francisco

Most of the really outrageous stuff comes after the period I’ve been investigating, after Seroquel is on the market. So many threads! Damage control, spinning [or denying] weight gain and diabetes, extending their targeted population to mania, then bipolar disorders, then depression, etc. It’s a story of a corporate culture that has no connection with the impact of their decisions on their  patients  customers, dealing with a large segment of a medical specialty that has equally lost its way. This email from around the time Seroquel was approved exemplifies the depth of the plunge. It was a response to an investigator’s request for funding:

I’ve already posted the famous email congratulating Dr. Lisa Arvanitis’ "’smoke and Mirrors’ job" in obfuscating the weight gain data in the Trial 0015 report to the F.D.A. [and as the author of the published reports]. And there was Dr. Arvanitis’ own email musing about how to spin and muddle data so the Sales Reps could downplay weight gain. Unposted is this thread where they’re debating about burying Trial 0015 altogether [which they did]. I’ll just post one more. It’s Dr. Arvanitis again, a memo explaining how she’s going to spin Trial 0015 to the investigators who actually did the study to explain its disappearance. It’s a conscious lie:

I think the reason I keep picking Dr. Lisa Arvanitis’ communications is that though they’re nowhere near the most devious or the diciest, she was the Physician in charge of the Seroquel project at Zeneca. She shepherded the drug all the way through, wrote [?] the papers, wrote-up the "cursed" Trial 0015, buried it. And I can find no place where it seemed to dawn on her that they had a dog of a drug – a weak antipsychotic that makes patients gain a lot of weight and sometimes develop Diabetes, something dangerous. In this Memo, she doesn’t seem to register that she’s becoming a part of what’s wrong in the world. Even though she was the physician in charge, she was as much a part of the Sales and Marketing department as anyone else – even before they made it official. I doubt this was what the little girl Lisa thought about when she dreamed of being a doctor as a child, but she took to it like a duck takes to water.

And she was part of a team of people at Zeneca that set a tone, a corporate course to move ahead no matter what got in their way. Seroquel was Zeneca‘s first venture into the psychiatric drug world. In this first campaign, they succeeded in keeping the ball rolling no matter the obstacle, and in doing so set trajectory of deceit for Zeneca cum AstraZeneca that pushed Seroquel into becoming a legendary moneymaker – now given to people who can’t even spell the name of the disease it was developed to treat, much less have it. Each of their little decisions back then made almost automatically has come back to haunt them in the rip-tide of lawsuits. They have little defense, and yet the profits keep rising.

Seroquel was approved on September 26, 1997. I consider that to be the "end of the beginning," but I’m taking a break for a while from the Seroquel story [It's not good for my mental health]. I expect I’ll be back on it sooner than I think. There are several points I’d like to pursue: How did a weak, moderately toxic, Atypical Antipsychotic get to be a drug used in Depression? What does this story say about the Clinical Trials world and evidence-based medicine? But most of all, "Why do people take it?" They wouldn’t stay on an older antipsychotic no matter what the ad said. What is it that Seroquel [and Abilify or Zyprexa] do for people that makes them want to keep taking the drugs? I know it’s not its effectiveness in Schizophrenia, and I doubt that it has anything to do with it being an Antidepressant. And other than apparently being a really good sleeping pill, I don’t know the answer to that last question…

 

http://1boringoldman.com/index.php/2011/02/14/seroquel-xi-through-a-glass-darkly%E2%80%A6/

Seroquel X: Matters Cerebral (Serebral)

Written By: 1 Boring Old Man

Posted on Sunday 13 February 2011

So I’m taking a break from the Egyptian Revolution and watching one of my daughter’s friends on the Grammy’s, but on the side of my mind, I’m working up a resentment that we don’t get to see a scattergram of the patient’s weight gain plotted as a function of when they dropped out of Trial 0015. And so I look one more time to see if the raw study data is on the Internet. It’s not there any more than it was the last time I looked, but I see something called 04_Exhibit27 that I’ve not seen before. So I open it up. It’s an email from Dr. Arvanitis [August 13, 1997] about weight gain. I’ll let it speak for itself:

 

I’m sitting here almost 14 years later trying to figure out how much weight gain they knew about before the submitted their approval application in 1997. Lisa Arvanitis,  on the other hand, is sitting  back there at the time with weight gain information analyzed in every way possible [including my scattergram!]. They even had more than I knew from OLE [Open Label Extension - Zeneca gives medication away  free to people after the trial ends who want it and continue to collect data]. And what they’re pondering is how to turn their weight gain problem into an asset? Now that’s hubris.

What we learn is that the incidence of "Clinically Significant Weight Gain" at 52 weeks is 45% [and rising]. They’re brain-storming around trying to figure out some way to spin the weight gain story so the sales reps will have something upbeat to say about it, so she throws out some ideas about creative data-manipulation. But alas – reality intrudes on her fantasy…

In the published reports, she had already explained weight gain repeatedly.

In Trial 0006:
^{"Treatment with ICI 204,636 was associated with clinically significant weight gain (an increase of 7% or more from baseline weight) in 25% of patients compared with 4% of placebo-treated patients. Average weights at endpoint represented a change from baseline of +5.5 kg for ICI 204,636-treated patients and +0.5 kg for patients in the placebo group… Patients treated with ICI 204,636 gained, on average, 3.1 kg, and 24% had clinically significant increases in body weight of 7% or more. However, weight gain is not uncommon in schizophrenic patients treated with antipsychotic agents and has been reported in as many as one-third of patients treated with clozapine."}
In Trial 0008:
^{"Treatment with quetiapine was associated with clinically significant weight gain (an increase of >7% from baseline weight) in 25% of the patients in the high-dose group compared with 16% in the low-dose group and 5% in the placebo group… Patients treated with quetiapine had a mean weight gain of 2 kg, compared with 0.1 kg for patients in the placebo group; however, weight gain did not necessitate withdrawal of treatment for any patient and may or may not have been clinically important during the 6-week period. Often weight gain in patients treated for acute psychosis seems more a function of a return to preexacerbation status and other aspects of well-being associated with improvement in psychosis rather than of treatment."}
In Trial 0013:
^{"Mean increases in weight with quetiapine, from low to high dose, were +0.9, +2.9, +2.0, +2.6, and +2.3 kg, respectively, and were greater than those seen with haloperidol (+0.3 kg) or placebo (-0.8 kg). Increases from baseline of 7% or greater were considered clinically significant and were seen in greater proportions of quetiapine-treated patients: from low to high dose in 11%, 17%, 10%, 16%, and 13% versus 4% with haloperidol and 6% with placebo. Changes did not necessitate treatment withdrawal or appear dose-related on the basis of descriptive statistics… Although quetiapine was associated with a greater mean weight gain compared with haloperidol and placebo, no patients were withdrawn as a result. When reported as an adverse event, weight gain appeared to be related to dose, but no clear dose-response relationship was evident relative to clinically significant weight gain. Generally mean increases were greater at day 42 for patients who completed the trial (1.5-4.5 kg) than for patients who withdrew. In any case, weight gain over a 6-week period may or may not be clinically significant given that it may be a function of well-being resulting from improvement in psychosis."}
And in the Trial 0015 Report they sent the F.D.A.:
^{"There also appeared to be a dose-related increase in the proportion of patients with clinically significant weight gain among SEROQUEL groups. Clinically significant weight gain, which was associated with SEROQUEL treatment, is often seen during treatment with antipsychotic agents."}

What a naive question I asked a few posts back, "Did they cheat?" No need to summarize the evidence to answer that one anymore. "Yeah, they cheated – a lot"… 

 

http://1boringoldman.com/index.php/2011/02/13/seroquel-x-matters-serebral/

Seroquel IX: Weighty Matters

Written By: 1 Boring Old Man

Posted on Sunday 13 February 2011

Note: The graphics in this post are from three F.D.A. documents and one on the psychrights site. The tables from the F.D.A. documents have been reformatted to be readable, but the substance is unaltered. Click the graphic to see the original. I haven’t altered the graphics from the psychrights document because that document itself is >40 MB and needs an overnight download. Here are links to those primary sources: • [FDA] Statistical Review and Evaluation • [FDA] Review and Evaluation of Clinical Data • [FDA] Review and Evaluation of Clinical Data: Appendixes • [psychrights] Trial 0015

One thing looking at all of these documents has done for me is restore my faith in the support staff at the F.D.A. Their reports are thorough and have the information that’s required. I’ll pick a few bones with the reviewers who looked at and assimilated it, but on a whole they seemed to be doing the job of giving the decision makers what they needed to reach conclusions.

Weight gain was one of their statistically significant adverse effects:

 

In the Review and Evaluation of Clinical Data, they comment:

Here are the tables they reference in the Appendix:

 

 

^{I’ve been trying not to be too picky in this series. "Hindsight is 20/20" they say – and after the fact, it’s real easy to criticize  others for missing things that you would’ve probably missed yourself if in a similar situation. And, by the way, no one would call me an obsessive person. If you saw the little office in our cabin where I’m typing right now, you’d see that yourself. The only really well organized thing in the room is on the monitor screen where this post is being put together. But I feel a picky obsessive attack coming on, because I smell a rat. These tables just don’t tell the whole story.}

The rat I smelled was n. n doesn’t make sense to me. In the report, there are lengthy explanations of the number of subjects exposed to Quetiapine [Seroquel] and the various databases they used. The general gist of things was that there was an Efficacy database and a Safety database – the former we know about, the latter is everybody in any study, but there were exceptions to what "everybody" meant. Again, after more readings than I’d care to admit, I couldn’t make any sense out of it. I don’t mean to accuse them of hiding something in the F.D.A. report, I just couldn’t follow what they were saying. The point is that nothing that I could find added up the the  n values in these tables. I don’t know if this is only the four efficacy studies or some other fraction of the whole pie. So I gave up and went for the part that mattered – Trial 0015 – the only study that lasted more than six weeks. I downloaded the 40+ MB file overnight and looked for the part about weight. Here are the combined parts of the report [pdf pages 142-144] that relate to weight:

 

Not what I would call a particularly clear presentation of the facts. I’ve tried to help them along with data presentation methodology. First, the upper table [Weight Gain at Final Evaluation]:

Of course this is a bit absurd. This was a one year study with people dropping out all along the way, so the table isn’t meaningful. What we need to see is Weight Gain at Final Evaluation versus Time of Final Evaluation. Even at that, the weight gain is apparent:

Next, they embed the Ranges of Weight Gain at Final Evaluation. Here’s a tabular view:

Same Criticism. Where’s the Time dimension?

Finally in the bottom table, they give us the % whose weight gain fits their definition of "Clinically Significant" [>7% baseline weight]. This is the most obfuscated of the bunch, because the majority of subjects dropped out early [before having time to really pork-up].

Even at that, there was still an impressive weight gain with increasing Seroquel dose.

The point is that no matter how hard we try to get at what we want to know [weight gain plotted against time of withdrawal for each group], it’s just not possible to figure it out. In each case, they’ve hidden the time dimension [in fact, used it to bring down the other values]. They show us that there’s weight gain, and that it’s dose related, but they hide the extent of the damage [on purpose]. This is data massage at the least, more like data camouflage. They know what matters; they know the answer; and they won’t show it to us. I think the ‘weight thing’ is the real "’smoke and mirrors’ job"

http://1boringoldman.com/index.php/2011/02/13/seroquel-ix-weighty-matters/